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Sample records for mmp-9 neutrophil gelatinase-associated

  1. Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias

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    Bouchet, Sandrine; Bauvois, Brigitte, E-mail: brigitte.bauvois@crc.jussieu.fr [INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris 75006 (France)

    2014-04-04

    Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  2. Circulating levels of matrix metalloproteinase-9 (MMP-9, neutrophil gelatinase-associated lipocalin (NGAL and their complex MMP-9/NGAL in breast cancer disease

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    Nonni Afroditi

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9 is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p Conclusion These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

  3. Neutrophil Gelatinase-Associated Lipocalin (NGAL, Pro-Matrix Metalloproteinase-9 (pro-MMP-9 and Their Complex Pro-MMP-9/NGAL in Leukaemias

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    Sandrine Bouchet

    2014-04-01

    Full Text Available Matrix metalloproteinase (MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9 also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro-MMP-9 (active and latent forms and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  4. of Matrix Metalloproteinase-9 and Neutrophil Gelatinase-Associated Lipocalin

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    De Caridi Giovanni

    2015-01-01

    Full Text Available The association of an axillary artery aneurysm and an abdominal aortic aneurysm is extremely rare. In this study, we describe this association in a 69 year-old-man. We measured this patient’s metalloproteinases (MMPs and Neutrophil Gelatinase - Associated Lipocalin (NGAL levels over a three years period before the abdominal aortic aneurysm rupture. We speculate that high serium levels of MMPs and NGAL may have a prognostic role and may predict aneurysm rupture in patients with an uncommon association of arterial aneurysms.

  5. A self-propagating matrix metalloprotease-9 (MMP-9 dependent cycle of chronic neutrophilic inflammation.

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    Xin Xu

    Full Text Available BACKGROUND: Chronic neutrophilic inflammation is a poorly understood feature in a variety of diseases with notable worldwide morbidity and mortality. We have recently characterized N-acetyl Pro-Gly-Pro (Ac-PGP as an important neutrophil (PMN chemoattractant in chronic inflammation generated from the breakdown of collagen by the actions of MMP-9. MMP-9 is present in the granules of PMNs and is differentially released during inflammation but whether Ac-PGP contributes to this ongoing proteolytic activity in chronic neutrophilic inflammation is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing isolated primary blood PMNs from human donors, we found that Ac-PGP induces significant release of MMP-9 and concurrently activates the ERK1/2 MAPK pathway. This MMP-9 release is attenuated by an inhibitor of ERK1/2 MAPK and upstream blockade of CXCR1 and CXCR2 receptors with repertaxin leads to decreased MMP-9 release and ERK 1/2 MAPK activation. Supernatants obtained from PMNs stimulated by Ac-PGP generate more Ac-PGP when incubated with intact collagen ex vivo; this effect is inhibited by an ERK1/2 pathway inhibitor. Finally, clinical samples from individuals with CF demonstrate a notable correlation between Ac-PGP (as measured by liquid chromatography-tandem mass spectrometry and MMP-9 levels even when accounting for total PMN burden. CONCLUSIONS/SIGNIFICANCE: These data indicate that ECM-derived Ac-PGP could result in a feed-forward cycle by releasing MMP-9 from activated PMNs through the ligation of CXCR1 and CXCR2 and subsequent activation of the ERK1/2 MAPK, highlighting for the first time a matrix-derived chemokine (matrikine augmenting its generation through a discrete receptor/intracellular signaling pathway. These findings have notable implications to the development unrelenting chronic PMN inflammation in human disease.

  6. Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach

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    Otto, Gordon P.; Hurtado-Oliveros, Jorge; Chung, Ha-Yeun; Knoll, Kristin; Neumann, Thomas; Müller, Hans J.; Herbsleb, Marco; Kohl, Matthias; Busch, Martin; Sossdorf, Maik; Claus, Ralf A.

    2015-01-01

    Acute kidney injury (AKI) during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL) is discussed as new biomarker for AKI diagnosis, but during inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated. In-vitro blood stimulations with IL-6, lipopolysaccharide, NGAL or its combinations were performed to investigate cause-effect-relationship. Plasma-NGAL levels were stronger associated with inflammation markers including IL-6 (Sepsis: r=0.785 PSepsis: r=0.714 Pdetection during severe inflammation - indeed it has to be interpreted carefully within this setting - but additionally might offer therapeutic potential. PMID:25893429

  7. Systemic and urinary neutrophil gelatinase-associated lipocalins are poor predictors of acute kidney injury in unselected critically ill patients.

    NARCIS (Netherlands)

    Royakkers, A.A.; Bouman, C.S.; Stassen, P.M.; Korevaar, J.C.; Binnekade, J.M.; Hoek, W. van der; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.

    2012-01-01

    Background. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine have been suggested as potential early predictive biological markers of acute kidney injury (AKI) in selected critically ill patients. Methods. We performed a secondary analysis of a multicenter prospective observationa

  8. Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation

    DEFF Research Database (Denmark)

    Magnusson, Nils E; Hornum, Mads; Jørgensen, Kaj Anker;

    2012-01-01

    Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14 heal...

  9. PLASMA NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN AS AN EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN SNAKE BITE

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    Thamarai

    2014-12-01

    Full Text Available INTRODUCTION: Acute kidney injury due to snake bite represents a frequent and devastating problem. Currently, Acute Kidney Injury is diagnosed by biochemical monitoring of increase in serum creatinine. Increase in serum creatinine represents a late indication of a functional change in glomerular function rate. Studies have shown that Neutrophil Gelatinase Associated Lipocalin has been found to be very useful for the detection of acute kidney injury within few hours of nephrotoxic insult. Limited information, however, is available regarding the study of plasma Neutrophil Gelatinase-Associated Lipocalin in snake bite. AIM: The purpose of the study was to estimate the diagnostic accuracy of plasma Neutrophil Gelatinase-Associated Lipocalin as an early biomarker of Acute Kidney Injury in patients with snake bite and to correlate with serum creatinine. If early detection of Acute Kidney Injury occurs, it can be followed by effective treatment modalities to abort the development or limit the severity of AKI. Therefore this study was designed to explore the importance of pNGAL in cases of snake bite induced AKI. MATERIALS AND METHODS: A prospective observational study was designed to study the patients admitted for the treatment of snakebite within 6 hours in a tertiary care hospital. Patients admitted for snake bite were followed by estimation of pNGAL on day 1 and serum creatinine from the period of admission for up to 5 days. A total of 130 snake bite patients were enrolled and 100 were included in the final study. Snake bite patients were classified into two groups based on the occurrence and absence of AKI. Plasma NGAL and serum creatinine was estimated by solid phase Enzyme Linked Immunosorbent Assay method and Jaffe`s method respectively. Data were entered into the excel sheet and analyzed statistically using statistical package for the social sciences (SPSS version 17. RESULTS:Among 100 snake bite patients 64 individuals had elevated p

  10. Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats

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    Arellano-Buendía, Abraham Said; García-Arroyo, Fernando Enrique; Cristóbal-García, Magdalena; Loredo-Mendoza, María Lilia; Tapia-Rodríguez, Edilia; Sánchez-Lozada, Laura Gabriela; Osorio-Alonso, Horacio

    2014-01-01

    Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction. Methods. Diabetes was induced in rats by streptozotocin administration (50 mg/kg). Oxidative stress was assessed by measuring the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD); additionally, expression levels of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), and oxidized protein (OP) were quantified. Whole glomerular filtration rate (GFR) was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin (uOPN), and N-acetyl-β-D-glucosaminidase (uNAG) was also determined. Results. Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes. PMID:25243053

  11. Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats

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    Abraham Said Arellano-Buendía

    2014-01-01

    Full Text Available Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction. Methods. Diabetes was induced in rats by streptozotocin administration (50 mg/kg. Oxidative stress was assessed by measuring the activity of catalase (CAT, glutathione peroxidase (GPx, and superoxide dismutase (SOD; additionally, expression levels of 3-nitrotyrosine (3-NT, 4-hydroxynonenal (4-HNE, and oxidized protein (OP were quantified. Whole glomerular filtration rate (GFR was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL, osteopontin (uOPN, and N-acetyl-β-D-glucosaminidase (uNAG was also determined. Results. Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes.

  12. Neutrophil Gelatinase-Associated Lipocalin Concentration in Vaginal Fluid: Relation to Bacterial Vaginosis and Vulvovaginal Candidiasis.

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    Beghini, Joziani; Giraldo, Paulo C; Linhares, Iara M; Ledger, William J; Witkin, Steven S

    2015-08-01

    Neutrophil gelatinase-associated lipocalin (NGAL) is a component of innate immunity that prevents iron uptake by microorganisms. We evaluated whether NGAL was present in vaginal fluid and whether concentrations were altered in women with bacterial vaginosis (BV) or vulvovaginal candidiasis (VVC). Vaginal secretions from 52 women with VVC, 43 with BV, and 77 healthy controls were assayed by enzyme-linked immunosorbent assay for NGAL and for concentrations of L-lactic acid. The median concentration of NGAL in vaginal fluid was significantly higher in control women (561 pg/mL) than in women with BV (402 pg/mL; P = .0116) and lower in women with VVC (741 pg/mL; P = .0017). Median lactic acid levels were similar in controls (0.11 mmol/L) and women with VVC (0.13 mmol/L) and were lower in women with BV (0.02 mmol/L; P < .0001). The NGAL and lactic acid concentrations were highly correlated (P < .0001). A decrease in Lactobacilli and/or lactic acid plus the absence of leukocytes results in lower vaginal NGAL levels that might facilitate the growth of bacteria associated with BV. © The Author(s) 2015.

  13. Correlation of serum neutrophil gelatinase associated lipocalin with disease severity in hypertensive disorders of pregnancy

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    Rekha Sachan

    2014-01-01

    Full Text Available Background: Vascular endothelial dysfunction is considered central to the pathogenesis of hypertensive disorders of pregnancy (HDP. Serum level of neutrophil gelatinase-associated lipocalin (NGAL is closely related to endothelial injury. The aim of this study was to examine the correlation of serum NGAL with disease severity in HDP. Materials and Methods: This prospective case-control study was carried out for one year. After informed consent, ethical clearance, total 1,850 pregnant women were screened. Analysis was performed on 142 cases of HDP and 31 healthy controls. Quantitative measurement of serum NGAL levels was done by the enzyme linked immunosorbent assay (ELISA technique, by using sandwich ELISA kit. Results: Mean serum NGAL value in patients with oliguria was significantly higher when compared with non-oliguric patients (P < 0.001. Serum NGAL had a positive correlation with systolic blood pressure (r ~ 0.5973, diastolic blood pressure (r ~ 0.6195, blood urea (r ~ 0.4392, serum creatinine (r ~ 0.6112, serum uric acid (r ~ 0.3878. Sensitivity and specificity of serum NGAL using a cut-off value of 545 pg/ml, for the diagnosis of HDP, was 97.89% and 93.55% respectively, using 95% confidence interval. Conclusion: Between the two groups, we found that serum NGAL had a positive correlation with disease severity and better sensitivity and specificity in the evaluation of HDP.

  14. Renal neutrophil gelatinase associated lipocalin expression in lipopolysaccharide-induced acute kidney injury in the rat

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    Han Mei

    2012-06-01

    Full Text Available Abstract Background Neutrophil gelatinase associated lipocalin (NGAL is a highly predictive biomarker of acute kidney injury. To understand the role of NGAL in renal injury during sepsis, we investigated the temporal changes and biological sources of NGAL in a rat model of acute kidney injury, and explored the relationship between renal inflammation, humoral NGAL and NGAL expression during endotoxemia. Methods To induce acute renal injury, rats were treated with lipopolysaccharide (LPS, 3.5 mg/kg, ip, and the location of NGAL mRNA was evaluated by in situ hybridization. Quantitative RT-PCR was also used to determine the dynamic changes in NGAL, tumor necrosis factor α (TNFα and interleukin (IL-6 mRNA expression 1, 3, 6, 12, and 24 hours following LPS treatment. The correlation among NGAL, TNFα and IL-6 was analyzed. Urinary and plasma NGAL (u/pNGAL levels were measured, and the relationship between humoral NGAL and NGAL expression in the kidney was investigated. Results Renal function was affected 3–12 hours after LPS. NGAL mRNA was significantly upregulated in tubular epithelia at the same time (P P P P Conclusions NGAL upregulation is sensitive to LPS-induced renal TNFα increase and injury, which are observed in the tubular epithelia. Urinary NGAL levels accurately reflect changes in NGAL in the kidney.

  15. Hubungan Kadar Albumin Serum dengan Neutrophil Gelatinase-Associated Lipocalin Urine pada Penderita Sindrom Nefrotik Anak

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    Deasy Nurisya

    2014-09-01

    Full Text Available Neutrophil gelatinase-associated lipocalin (NGAL is a biological marker found in kidney damage that increases in proximal tubular damage. The purpose of this study was to analyze the correlation between serum albumin and urine NGAL (uNGAL levels in children with NS at initial presentation or relapse. Subjects in this study were 1−14 year-old children with NS. An observational analytical study with cross sectional design was conducted in the Pediatric Department of Dr. Hasan Sadikin General Hospital Bandung and Bandung City Public Hospital from September 2011 to March 2012. The serum albumin level and uNGAL level were measured using bromcresol green method and enzyme-linked immunosorbent assay (ELISA, respectively. Data were analyzed using Pearson correlation test on normal distribution data. Subjects consisted of 14 boys and 10 girls. Mean serum albumin and uNGAL levels were 1.37 (SD 0.33 g/dL and 2,719.37 (SD 3,781.82 ng/mL, respectively. There was a significant correlation between decreased albumin level and elevated uNGAL level (r=−0.519, p=0.009. In conclusion, the lower the albumin level, the higher the uNGAL level. An awareness should be developed towards the possibility that hypoalbuminemia in children with NS might decrease renal function.

  16. Urine neutrophil gelatinase-associated lipocalin (NGAL as a biomarker for acute canine kidney injury

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    Lee Ya-Jane

    2012-12-01

    Full Text Available Abstract Background Biomarkers for the early prediction of canine acute kidney injury (AKI are clinically important. Recently, neutrophil gelatinase-associated lipocalin (NGAL was found to be a sensitive biomarker for the prediction of human AKI at a very early stage and the development of AKI after surgery. However, NGAL has not yet been studied with respect to dog kidney diseases. The application of NGAL canine AKI was investigated in this study. Results The canine NGAL gene was successfully cloned and expressed. Polyclonal antibodies against canine NGAL were generated and used to develop an ELISA for measuring NGAL protein in serum and urine samples that were collected from 39 dogs at different time points after surgery. AKI was defined by the standard method, namely a serum creatinine increase of greater than or equal to 26.5 μmol/L from baseline within 48 h. At 12 h after surgery, compared to the group without AKI (12 dogs, the NGAL level in the urine of seven dogs with AKI was significantly increased (median 178.4 pg/mL vs. 88.0 pg/mL, and this difference was sustained to 72 h. Conclusion As the increase in NGAL occurred much earlier than the increase in serum creatinine, urine NGAL seems to be able to serve as a sensitive and specific biomarker for the prediction of AKI in dogs.

  17. Serum cystatin C and neutrophil gelatinase-associated lipocalin in predicting the severity of coronary artery disease in diabetic patients

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    OKYAY, Kaan; Y?ld?r?r, Aylin; ?i?ek, Mutlu; Ayd?nalp, Alp; M?derriso?lu, Haldun

    2015-01-01

    Objective: Cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) are biomarkers of renal functions. We evaluated their roles in predicting the severity of coronary artery disease (CAD). Methods: Fifty-two consecutive type 2 diabetic patients (32 males, 65.7?8.6 years) who underwent coronary angiography (CAG) for stable CAD were included in this single-center, prospective, cross-sectional study. Patients with an estimated glomerular filtration rate

  18. Waist circumference and neutrophil gelatinase-associated lipocalin in late-life depression.

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    Marijnissen, Radboud M; Naudé, Petrus J W; Comijs, Hannie C; Schoevers, Robert A; Oude Voshaar, Richard C

    2014-03-01

    Both visceral obesity and depression are associated with impaired health and excess mortality, possibly through overlapping pathophysiological mechanisms like adipose tissue derived inflammatory markers. These results, however, are primarily based on population-based surveys, often restricted to a young population and depression severity scales instead of patients with established diagnosis of depressive disorder. We examined the relation between waist circumference and late-life depression using the baseline data of The Netherlands Study of Depression in Older people (NESDO). Psychopathology has been assessed with Composite International Diagnostic Interview version 2.1. Adjusted for age, sex, education, lifestyle (smoking, alcohol, physical activity), drug use, cognition and chronic diseases as well as adjusted for body mass index (BMI), analysis of covariance showed that depressed older patients (n=376) had a significantly lower waist circumference (WC) compared to their non-depressed comparisons (n=130): estimated marginal mean (SE)=93.9 (0.5) versus 97.8 (0.8) cm (F=15.9; df=1467; p<.001). Multiple linear regression analyses within the depressed group showed that both, depression severity (Inventory of Depressive Symptoms) as well as duration-related depression characteristics (age of onset, duration of illness, life-time comorbid dysthymia), were associated with the WC. Only the severity of depressive symptoms remained significant after further adjusted for the BMI. Interestingly, a recently discovered adipokine, Neutrophil Gelatinase-Associated Lipocalin (NGAL), was associated with late-life depression, but only in the subgroup of patients with a pathologically increased WC. Population-based findings on the positive association between obesity and depressive symptoms can thus not be generalised to a clinical sample of depressed older patients. The impact of the WC on course and treatment outcome of late-life depression should be examined in clinical samples

  19. Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

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    Kim, Hanah; Hur, Mina; Lee, Seungho; Marino, Rossella; Magrini, Laura; Cardelli, Patrizia; Struck, Joachim; Bergmann, Andreas; Hartmann, Oliver; Di Somma, Salvatore

    2017-09-01

    Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.

  20. Neutrophil Gelatinase-Associated Lipocalin: Ready for Routine Clinical Use? An International Perspective

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    Ronco, Claudio; Legrand, Matthieu; Goldstein, Stuart L.; Hur, Mina; Tran, Nam; Howell, Eric C.; Cantaluppi, Vincenzo; Cruz, Dinna N.; Damman, Kevin; Bagshaw, Sean M.; Di Somma, Salvatore; Lewington, Andrew

    2016-01-01

    Acute kidney injury (AKI) remains a challenge in terms of diagnosis and classification, its morbidity and mortality remaining high in the face of improving clinical protocols. Current clinical criteria use serum creatinine (sCr) and urine output to classify patients. Ongoing research has identified novel biomarkers that may improve the speed and accuracy of patient evaluation and prognostication, yet the route from basic science to clinical practice remains poorly paved. International evidence supporting the use of plasma neutrophil gelatinase-associated lipocalin (NGAL) as a valuable biomarker of AKI and chronic kidney disease (CKD) for a number of clinical scenarios was presented at the 31st International Vicenza Course on Critical Care Nephrology, and these data are detailed in this review. NGAL was shown to be highly useful alongside sCr, urinary output, and other biomarkers in assessing kidney injury; in patient stratification and continuous renal replacement therapy (CRRT) selection in paediatric AKI; in assessing kidney injury in conjunction with sCr in sepsis; in guiding resuscitation protocols in conjunction with brain natriuretic peptide in burn patients; as an early biomarker of delayed graft function and calcineurin inhibitor nephrotoxicity in kidney transplantation from extended criteria donors; as a biomarker of cardiovascular disease and heart failure, and in guiding CRRT selection in the intensive care unit and emergency department. While some applications require further clarification by way of larger randomised controlled trials, NGAL nevertheless demonstrates promise as an independent biological marker with the potential to improve earlier diagnosis and better assessment of risk groups in AKI and CKD. This is a critical element in formulating quick and accurate decisions for individual patients, both in acute scenarios and in long-term care, in order to improve patient prognostics and outcomes. PMID:25012891

  1. Neutrophil Gelatinase-Associated Lipocalin: Its Response to Hypoxia and Association with Acute Mountain Sickness

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    Adrian Mellor

    2013-01-01

    Full Text Available Acute Mountain Sickness (AMS is a common clinical challenge at high altitude (HA. A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n=22 undertaking 6 hours exercise at near sea-level (SL; a cohort (n=14 during 3 hours of normobaric hypoxia (FiO2 11.6% and on two trekking expeditions (n=52 to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range rose significantly (P<0.001 from 68 ± 14 (60–102 at 1300 m to 183 ± 107 (65–519; 143 ± 66 (60–315 and 150 ± 71 (60–357 at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n=7, mild AMS (n=16 or no AMS (n=23: 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P=0.009 for severe versus no AMS; P=0.026 for mild versus no AMS. In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS.

  2. Urinary neutrophil gelatinase-associated lipocalin is a biomarker of delayed graft function after kidney transplantation

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    Capelli I

    2017-01-01

    Full Text Available Irene Capelli, Olga Baraldi, Giorgia Comai, Elisa Sala, Maria Cappuccilli, Chiara Donadei, Vania Cuna, Maria Laura Angelini, Gabriele Donati, Gaetano La Manna Department of Experimental Diagnostic and Specialty Medicine (DIMES, Nephrology, Dialysis and Renal Transplant Unit, St Orsola Hospital, University of Bologna, Bologna, Italy Background: Acute kidney injury occurring after kidney transplantation frequently leads to delayed graft function with detrimental long-term effects on graft survival. Neutrophil gelatinase-associated lipocalin (NGAL has been validated as a biomarker for posttransplant acute kidney injury. This observational study aimed to assess the effectiveness of urinary NGAL as a predictive marker of delayed graft function.Materials and methods: Forty-three consecutive patients who received renal transplant were included in the study. Urine samples were collected before transplant (if available and at days 1, 3, 7, 14, and 30 after transplant, and urinary NGAL levels were quantified by enzyme-linked immunosorbent assay.Results: Urinary NGAL progressively decreased after transplant in patients with both delayed and immediate graft function. However, urinary NGAL concentration remained significantly higher in the presence of delayed graft function in the first 14 days after transplant. The area under the receiver operating characteristic curve showed that the ability of urinary NGAL to predict delayed graft function was accurate at 1st and 3rd days after transplant.Conclusion: The relative decrease of urinary NGAL concentration rather than its absolute value may be relevant to predict delayed graft function after renal transplant. In particular, urinary NGAL area under the curve for 3 days seems to be a more valuable parameter of decision making in the early posttransplant period. Keywords: area under the curve, delayed graft function, immediate graft function, kidney transplant, NGAL, acute kidney injury

  3. Plasma Neutrophil Gelatinase-Associated Lipocalin and Acute Postoperative Kidney Injury in Adult Cardiac Surgical Patients

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    Perry, Tjörvi E.; Muehlschlegel, Jochen D.; Liu, Kuang-Yu; Fox, Amanda A.; Collard, Charles D.; Shernan, Stanton K.; Body, Simon C.

    2010-01-01

    BACKGROUND Acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery is associated with increased postoperative morbidity and mortality. We hypothesized that increased plasma neutrophil gelatinase-associated lipocalin (NGAL) measured immediately after separating from cardiopulmonary bypass (CPB) would predict AKI after CABG surgery. METHODS In a retrospective observational study, we examined the value of plasma NGAL measured after CPB for predicting the risk of developing AKI (defined as a ≥50% increase in serum creatinine from preoperative levels) in 879 patients after CABG surgery using multivariable logistic regression. Area under the curve of receiver operating characteristic curves was analyzed to assess sensitivities, specificities, and cutoff points for postoperative plasma NGAL levels to predict AKI. RESULTS Seventy-five patients (8.6%) developed postoperative AKI. Plasma NGAL levels measured after CPB were higher in patients who subsequently developed AKI than in those who did not (AKI: 268.8 ng/mL [207.5–459.5 ng/mL], median [interquartile range], vs no AKI: 238.4 ng/mL [172.0–319.1 ng/mL]; P postoperative day 4. An optimal serum plasma NGAL cutoff of 353.5 ng/mL at the post-CPB time point had a sensitivity of 38.7%, specificity of 81.5%, and a positive predictive value of 16.3% for predicting AKI. In our multivariate regression model, post-CPB plasma NGAL levels >353.5 ng/mL were independently associated with postoperative AKI (odds ratio, 2.3; 95% confidence interval, 1.5–6.5; P = 0.002). CONCLUSION An early increase of post-CPB plasma NGAL is associated with AKI in adult patients undergoing CABG surgery, although the sensitivity is low. Therefore, assessing early plasma NGAL alone has limited utility for predicting AKI in this patient population. PMID:20435938

  4. Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

    Institute of Scientific and Technical Information of China (English)

    Alessio; Strazzulla; Giuseppe; Coppolino; Concetta; Di; Fatta; Francesca; Giancotti; Giuseppina; D’Onofrio; Maria; Concetta; Postorino; Maria; Mazzitelli; Selma; Valerie; Mammone; Innocenza; Gentile; Laura; Rivoli; Eleonora; Palella; Tiziana; Gravina; Chiara; Costa; Vincenzo; Pisani; Vincenzo; De; Maria; Giorgio; Settimo; Barreca; Nadia; Marascio; Alfredo; Focà; Giorgio; Fuiano; Elio; Gulletta; Carlo; Torti

    2016-01-01

    AIM: To evaluate neutrophil gelatinase associated lipocalin(NGAL) in patients infected by hepatitis C virus(HCV) before and during treatment with directly acting antivirals(DAAs).METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate(e GFR). Then, NGAL and e GFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for nonparametric data. Differences in dichotomous variables were evaluated through χ~2 test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four(FIB-4), AST to platelet ratio index(APRI), and e GFR]. RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with e GFR 118.11 ng/d L were compared with those of NGAL ≤ 118.11 ng/d L, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis(P > 0.05). Linear correlation was found between NGAL and both age(P = 0.0475) and e GFR(P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for e GFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline(P = 0.0239).CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

  5. Association between plasma neutrophil gelatinase associated lipocalin level and obstructive sleep apnea or nocturnal intermittent hypoxia.

    Directory of Open Access Journals (Sweden)

    Kimihiko Murase

    Full Text Available BACKGROUND: Both obstructive sleep apnea (OSA and a novel lipocalin, neutrophil gelatinase associated lipocalin (Ngal, have been reported to be closely linked with cardiovascular disease and loss of kidney function through chronic inflammation. However, the relationship between OSA and Ngal has never been investigated. OBJECTIVES: To evaluate the relationship between Ngal and OSA in clinical practice. METHODS: In 102 patients, polysomnography was performed to diagnose OSA and plasma Ngal levels were measured. The correlations between Ngal levels and OSA severity and other clinical variables were evaluated. Of the 46 patients who began treatment with continuous positive airway pressure (CPAP, Ngal levels were reevaluated after three months of treatment in 25 patients. RESULTS: The Ngal level correlated significantly with OSA severity as determined by the apnea hypopnea index (r = 0.24, p = 0.01 and 4% oxygen desaturation index (ODI (r = 0.26, p = 0.01. Multiple regression analysis showed that the Ngal level was associated with 4%ODI independently of other clinical variables. Compliance was good in 13 of the 25 patients who used CPAP. Although the OSA (4%ODI: 33.1±16.7 to 1.1±1.9/h, p<0.01 had significantly improved in those with good compliance, the Ngal levels were not significantly changed (60.5±18.1 before CPAP vs 64.2±13.9 ng/ml after CPAP, p = 0.27. CONCLUSIONS: Plasma Ngal levels were positively associated with the severity of OSA. However, the contribution rate of OSA to systemic Ngal secretion was small and changes in Ngal levels appeared to be influenced largely by other confounding factors. Therefore, it does not seem reasonable to use the Ngal level as a specific biomarker of OSA in clinical practice.

  6. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL in Patients with Obstructive Sleep Apnea.

    Directory of Open Access Journals (Sweden)

    Manish R Maski

    Full Text Available Obstructive sleep apnea (OSA is a well-established risk factor for hypertension and cardiovascular morbidity and mortality. More recently, OSA has been implicated as an independent risk factor for chronic kidney disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL is a well-accepted early biomarker of subclinical kidney tubular injury, preceding an increase in serum creatinine. The goal of this study was to determine if an association exists between OSA and increased urinary NGAL levels.We prospectively enrolled adult patients from the sleep clinic of an academic medical center. Each underwent polysomnography and submitted a urine specimen upon enrollment. We measured NGAL and creatinine levels on all urine samples before participants received treatment with continuous positive airway pressure (CPAP, and, in a subset of OSA patients, after CPAP therapy. We compared the urinary NGAL/creatinine ratio between untreated participants with and without OSA, and within a subset of 11 OSA patients also after CPAP therapy.A total of 49 subjects were enrolled: 16 controls based on an apnea-hypopnea index (events with at least 4% oxygen desaturation; AHI-4% 5 events/hour (mean AHI-4% = 43.3 +/- 28.1. OSA patients had a higher mean body-mass index than the control group (36.58 +/- 11.02 kg/m2 vs. 26.81 +/- 6.55 kg/m2, respectively; p = 0.0005 and were more likely to be treated for hypertension (54.5% vs. 6.25% of group members, respectively; p = 0.0014. The groups were otherwise similar in demographics, and there was no difference in the number of diabetic subjects or in the mean serum creatinine concentration (control = 0.86 +/- 0.15 mg/dl, OSA = 0.87 +/- 0.19 mg/dl; p = 0.7956. We found no difference between the urinary NGAL-to-creatinine ratios among untreated OSA patients versus control subjects (median NGAL/creatinine = 6.34 ng/mg vs. 6.41 ng/mg, respectively; p = 0.4148. Furthermore, CPAP therapy did not affect the urinary NGAL

  7. Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach.

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    Gordon P Otto

    Full Text Available Acute kidney injury (AKI during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL is discussed as new biomarker for AKI diagnosis, but during inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated. In-vitro blood stimulations with IL-6, lipopolysaccharide, NGAL or its combinations were performed to investigate cause-effect-relationship. Plasma-NGAL levels were stronger associated with inflammation markers including IL-6 (Sepsis: r = 0.785 P < 0.001; chronic inflammation after anti-TNF: r = 0.558 P < 0.001, IL-8 (Sepsis: r = 0.714 P<0.004; healthy controls after exercise r = 0.786 P < 0.028; chronic inflammation before anti-TNF: r = 0.429 P < 0.041 and IL-10 (healthy controls before exercise: r = 0.791 P < 0.028 than with kidney injury or function. Correlation to kidney injury or function was found only in septic patients (for creatinine: r = 0.906 P < 0.001; for eGFR: r = -0.686 P = 0.005 and in patients with rheumatic disease after anti-TNF therapy (for creatinine: r = 0.466 P < 0.025. In stimulation assays with IL-6 and lipopolysaccharide plasma-NGAL was increased. Co-stimulation of lipopolysaccharide with plasma-NGAL decreased cellular injury (P < 0.05 and in trend IL-10 levels (P = 0.057. Septic mice demonstrated a significantly improved survival rate after NGAL treatment (P < 0.01. Plasma-NGAL seams to be strongly involved in inflammation. For clinical relevance, it might not only be useful for AKI detection during severe inflammation - indeed it has to be interpreted carefully within this setting - but additionally might offer therapeutic potential.

  8. Serum neutrophil gelatinase associated lipocalin during the early postoperative period predicts the recovery of graft function after kidney transplantation from donors after cardiac death.

    Science.gov (United States)

    Kusaka, Mamoru; Iwamatsu, Fumi; Kuroyanagi, Yoko; Nakaya, Miho; Ichino, Manabu; Marubashi, Shigeru; Nagano, Hiroaki; Shiroki, Ryoichi; Kurahashi, Hiroki; Hoshinaga, Kiyotaka

    2012-06-01

    Kidneys procured from donors after cardiac death hold great potential to expand the donor pool. However, they have not yet been fully used, in part due to the high incidence of delayed graft function. Although urine neutrophil gelatinase-associated lipocalin is a well-known early biomarker for renal injury after kidney transplantation, its usefulness is limited in cases with delayed graft function because of the unavailability of a urine sample. We evaluated serum neutrophil gelatinase-associated lipocalin as a potential biomarker to predict the functional recovery of kidneys transplanted from donors after cardiac death. Consecutive patients transplanted with a kidney from a living related (39), brain dead (1) or post-cardiac death (27) donor were retrospectively enrolled in the study. Serum samples were collected serially before and after kidney transplantation. Serum neutrophil gelatinase-associated lipocalin was measured using the ARCHITECT® assay. Average serum neutrophil gelatinase-associated lipocalin was markedly high during the pre transplantation period. It decreased rapidly after transplantation. The slope of the decrease correlated well with the recovery period. By analyzing ROC curves we determined cutoffs to predict immediate, slow or delayed graft function requiring hemodialysis for longer than 1 week with high sensitivity and specificity. These data suggest that serial monitoring of serum neutrophil gelatinase-associated lipocalin may allow us to predict graft recovery and the need for hemodialysis after kidney transplantation from a donor after cardiac death. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. IL-1α-induced microvascular endothelial cells promote neutrophil killing by increasing MMP-9 concentration and lysozyme activity.

    Science.gov (United States)

    Liu, Xiaoye; Dong, Hong; Wang, Mingming; Gao, Ying; Zhang, Tao; Hu, Ge; Duan, Huiqing; Mu, Xiang

    2016-02-01

    The recruitment of neutrophils by endothelial cells during infection has been extensively studied, but little is known about the regulation of neutrophils activity by endothelial cells. To examine the role of microvascular endothelial cells in neutrophil killing, we established a transmigration model using rat intestinal microvascular endothelial cells (RIMVECs) and measured the extracellular and intracellular killing of Escherichia coli, Lactobacillus acidophilus, and Staphylococcus aureus by transendothelial neutrophils. We observed that blood neutrophils engulfed bacteria but did not kill them, and lipopolysaccharide- or hemolysin-injured RIMVECs inhibited the extracellular and intracellular bactericidal activity of transendothelial neutrophils. In comparison, interleukin-1α-induced RIMVECs promoted the extracellular and intracellular killing activity of transendothelial neutrophils and significantly increased MMP-9 concentration and lysozyme activity in transendothelial neutrophils (p neutrophils and bacterial toxin damage of endothelial cells led to reduction in bactericidal activity of transendothelial neutrophils. These findings offered new insight into the role of endothelial cells in the bactericidal activity of neutrophils.

  10. Neutrophil Gelatinase Associated Lipocalin (NGAL) as a Biomarker. Does It Apply in Abdominal Aortic Aneurysms? A Review of Literature.

    Science.gov (United States)

    Karaolanis, Georgios; Moris, Demetrios; Palla, Viktoria-Varvara; Karanikola, Euridiki; Bakoyiannis, Chris; Georgopoulos, Sotirios

    2015-12-01

    Neutrophil gelatinase associated lipocalin (NGAL) as a protein derived from neutrophils has recently been the field of investigation in a wide range of diseases (renal disease, coronary artery disease, etc). The MEDLINE/PubMed database was searched for publications with the medical subject heading "NGAL" and keywords "Abdominal aortic aneurysm (AAA)," "biomarker," and "growth". We restricted our search to date. In this review, we included 38 articles and abstracts that were accessible and available in English. An effort to further explain the role of NGAL within AAA has been made. NGAL seems to be a hopeful marker for the pathogenesis and the progression of abdominal aortic aneurysms (AAAs), which has significant morbidity and mortality rates.

  11. Urinary Neutrophil Gelatinase-Associated Lipocalin and Progression of Diabetic Nephropathy in Type 1 Diabetic Patients in a Four-Year Follow-Up Study

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Hansen, Henrik Post; Jensen, Berit Ruud;

    2010-01-01

    Background: Neutrophil gelatinase-associated lipocalin (NGAL), a marker of renal tubular damage, predicts progression in non-diabetic chronic kidney. We evaluated urinary (u)-NGAL as a predictor of progression in diabetic nephropathy in type 1 diabetic (T1D) patients. Methods: As a substudy of a ...

  12. Neutrophil Gelatinase-Associated Lipocalin and its Receptors in Alzheimer's Disease (AD) Brain Regions: Differential Findings in AD with and without Depression

    NARCIS (Netherlands)

    Dekens, D.W.; Naude, P.J.; Engelborghs, S.; Vermeiren, Y.; Dam, D. Van; Oude Voshaar, R.C.; Eisel, U.L.; De Deyn, P.P.

    2016-01-01

    Co-existing depression worsens Alzheimer's disease (AD) pathology. Neutrophil gelatinase-associated lipocalin (NGAL) is a newly identified (neuro)inflammatory mediator in the pathophysiologies of both AD and depression. This study aimed to compare NGAL levels in healthy controls, AD without depressi

  13. Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril

    DEFF Research Database (Denmark)

    Nielsen, S E; Schjoedt, K J; Astrup, A S

    2010-01-01

    Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment...... on urinary NGAL was evaluated in diabetic nephropathy....

  14. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy

    Directory of Open Access Journals (Sweden)

    Patel ML

    2013-10-01

    Full Text Available ML Patel,1 Rekha Sachan,2 Radheyshyam Gangwar,3 Pushpalata Sachan,4 SM Natu51Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India; 2Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh, India; 3Department of Critical Care, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; 4Department of Physiology, King George's Medical University, Lucknow, Uttar Pradesh, India; 5Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh, IndiaAbstract: Hypertensive disorders of pregnancy (HDP remain one of the largest single causes of maternal and fetal morbidity and mortality, accounting for 16.1% of maternal deaths in developed countries. The aim of the study was to evaluate acute kidney injury (AKI in hypertensive disorders of pregnancy and to examine the correlation of serum neutrophil gelatinase-associated lipocalin (NGAL with acute kidney injury. This prospective case control study was carried out over a period of 1 year. After written, informed consent and ethical clearance, 149 cases of hypertensive disorders of pregnancy were screened, and seven were lost to follow-up. Acute kidney injury was detected in 88 cases and acute renal failure in 30 cases of HDP. Thirty-one healthy pregnant nonhypertensive women were enrolled as controls. Quantitative measurement of serum NGAL levels was done by enzyme linked immunosorbent assay technique using a sandwich enzyme-linked immunosorbent assay kit. As per the Kidney Diseases Improving Global Outcomes International guidelines acute kidney injury network (AKIN, 50 cases (42.37% of AKI stage I, 38 (32.2% cases of AKI stage II, and 30 (25.42% cases of renal failure were detected. Serum NGAL had a positive association with increasing proteinuria. It also had a positive correlation with systolic blood pressure (r~0.36, diastolic blood pressure (r~0.37, and serum creatinine (r~0

  15. Relationship of neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin levels with the presence and severity of the preeclampsia.

    Science.gov (United States)

    Artunc-Ulkumen, Burcu; Guvenc, Yesim; Goker, Asli; Gozukara, Ceyhun

    2015-11-01

    The aim of the present study was to evaluate changes in maternal serum neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin (PCT) concentrations in preeclampsia. This case-control study consisted of 40 preeclamptic and 40 healthy singleton pregnancies matched for age and body mass index. Serum NGAL and PCT levels were compared between the groups. Diagnostic performance and clinical association of these markers were evaluated. NGAL and PCT concentrations were significantly higher in preeclamptic group (p preeclampsia. There were significant positive correlation between these markers and mean arterial pressure (MAP) and spot urine protein excretion. There was negative correlation between NGAL and apgar scores and fetal birth weight. Pregnancies with higher NGAL (OR: 4.89; 95% CI: 1.81-13.21) and higher PCT (OR: 6.67; 95% CI: 2.44-18.21) concentrations had higher risk for preeclampsia. NGAL and PCT may be potential biomarkers for preeclampsia. Their levels increase significantly in preeclampsia and they are related to the severity of the disease. These results are in agreement with the generalized endothelial damage and persistant inflammatory status in preeclampsia. NGAL may also be an indicator for adverse neonatal outcomes with decreased placental hypoperfusion.

  16. Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL).

    Science.gov (United States)

    Arambašić, Jadranka; Mandić, Sanja; Debeljak, Željko; Mandić, Dario; Horvat, Vesna; Šerić, Vatroslav

    2016-01-01

    Acute pyelonephritis is a severe disease which is sometimes difficult to recognize based on clinical symptoms and routinely available diagnostic tests, especially in young children. The aim of this study was to assess the diagnostic value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a biomarker of acute pyelonephritis. In this case-control study we analyzed 134 children (median age 2.5 years) who were admitted to the Pediatric Clinic of University Hospital Centre Osijek, Croatia. Eighty of them had acute pyelonephritis, while 54 children had febrile state of different etiology including cystitis and they represented the control group. uNGAL, white blood cells, C-reactive protein, urinanalysis, urine culture, kidney ultrasound and a dimercaptosuccinic acid scintigraphic scan were done for each child. uNGAL was measured using chemiluminiscent microparticle immunoassay on ARHITECT i1000SR (Abbott Diagnostics, IL, USA). uNGAL values were significantly higher in children with acute pyelonephritis compared to the control groups (113.6 ng/mL vs. 10.2 ng/mL, ppyelonephritis from cystitis (cut-off 38.5 ng/mL), and for differentiation of cystitis from febrile states with etiology other than urinary tract infection (UTI) (cut-off 20.4 ng/mL). uNGAL can be a useful diagnostic biomarker in acute pyelonephritis in children, but also in differentiating cystitis from febrile states other than UTI.

  17. General anesthesia type does not influence serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in video laparoscopic bariatric surgery.

    Science.gov (United States)

    Fernandes, Adriano; Ettinger, João; Amaral, Fabiano; Ramalho, Maria José; Alves, Rodrigo; Módolo, Norma Sueli Pinheiro

    2014-12-01

    Video laparoscopic bariatric surgery is the preferred surgical technique for treating morbid obesity. However, pneumoperitoneum can pose risks to the kidneys by causing a decrease in renal blood flow. Furthermore, as in other surgical procedures, laparoscopic bariatric surgery triggers an acute inflammatory response. Neutrophil gelatinase-associated lipocalin is an early and accurate biomarker of renal injury, as well as of the inflammatory response. Anesthetic drugs could offer some protection for the kidneys and could attenuate the acute inflammatory response from surgical trauma. The objective of this study was to compare the effects of two types of anesthetics, propofol and sevoflurane, on the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in laparoscopic bariatric surgery. Sixty-four patients scheduled for laparoscopic bariatric surgery were randomized into two anesthesia groups and were administered either total intravenous anesthesia (propofol) or inhalation anesthesia (sevoflurane). In the perioperative period, blood samples were collected at three time points (before anesthesia, 6 hours after pneumoperitoneum and 24 hours after pneumoperitoneum) and urine output was measured for 24 hours. Acute kidney injuries were evaluated by examining both the clinical and laboratory parameters during the postoperative period. The differences between the groups were compared using non-parametric tests. ReBEC (http://www.ensaiosclinicos.gov.br/rg/recruiting/): RBR-8wt2fy None of the patients developed an acute kidney injury during the study and no significant differences were found between the serum neutrophil gelatinase-associated lipocalin levels of the groups during the perioperative period. The choice of anesthetic drug, either propofol or sevoflurane, did not affect the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in laparoscopic bariatric surgery.

  18. Plasma neutrophil gelatinase-associated lipocalin as an early biomarker for prediction of acute kidney injury after cardio-pulmonary bypass in pediatric cardiac surgery

    OpenAIRE

    Fatina I Fadel; Abdel Rahman, Azza M.O.; Mohamed, Mohamed Farouk; Habib, Sonia A.; Ibrahim, Mona H.; Sleem, Zeinab S.; Bazaraa, Hafez M; Soliman, Mohamed M.A.

    2012-01-01

    Introduction Cardiopulmonary bypass (CPB) surgery is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) represents a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in pediatric cardiac surgery. Material and methods The study included forty children aged 2 to 78 months undergoing CPB. They were divided into group I: pat...

  19. The diagnostic value of neutrophil gelatinase-associated lipocalin and hepcidin in bacteria translocation of liver cirrhosis.

    Science.gov (United States)

    Zhang, Jiangguo; Gong, Fengyun; Li, Ling; Zhao, Manzhi; Wu, Zhuhua; Song, Jianxin

    2015-01-01

    Bacterial translocation (BT) or bacterial DNA (bactDNA) translocation is a critical pathogenesis mechanism of spontaneous bacterial peritonitis. Studies of BT or bactDNA translocation are limited in humans. Neutrophil gelatinase associated lipocalin (NGAL) can efficiently distinguish bacterial and nonbacterial ascites in ascitic patients. Hepcidin is a useful marker of bacterial infection in the late-onset sepsis. However, the relationship between NGAL, hepcidin and BT was still unclear. In present study, the levels of NGAL, hepcidin and their relationship with BT or bactDNA translocation were investigated. Weekly doses of carbon tetrachloride (CCl4) were given to induce liver cirrhosis in Sprague-Dawley rats. Trypticase (blood) soy agars were used to culture bacteria. BactDNA was sequenced by ABIPRISM 310 automated sequencer. The levels of NGAL and hepcidin were assessed by ELISA. Receiver operating characteristic (ROC) curve was used to determine the cut-off values and compare the diagnostic performance of NGAL and hepcidin. 56 cirrhotic and 10 normal rats were included in this study. The levels of both two biomarkers were significantly higher in BT or bactDNA translocation group compared to non-translocation group. The area under ROC curve for the diagnosis of BT was 0.910 for serum NGAL, 0.858 for serum hepcidin and 0.940 for their combination, whereas that for the diagnosis of bactDNA translocation was 0.906 for NGAL, 0.779 for hepcidin and 0.950 for their combination, respectively. The combination of NGAL and hepcidin improved the ability to detect BT or bactDNA presence in MLNs and ascites. BT and the presence of bactDNA in MLNs were observed in a rat cirrhotic model. Serum NGAL and hepcidin can serve as sensitive and specific tests for diagnosis of BT or bactDNA translocation. NGAL in combination with hepcidin can improve the accuracy of diagnosis.

  20. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy.

    Science.gov (United States)

    Patel, Ml; Sachan, Rekha; Gangwar, Radheyshyam; Sachan, Pushpalata; Natu, Sm

    2013-01-01

    Hypertensive disorders of pregnancy (HDP) remain one of the largest single causes of maternal and fetal morbidity and mortality, accounting for 16.1% of maternal deaths in developed countries. The aim of the study was to evaluate acute kidney injury (AKI) in hypertensive disorders of pregnancy and to examine the correlation of serum neutrophil gelatinase-associated lipocalin (NGAL) with acute kidney injury. This prospective case control study was carried out over a period of 1 year. After written, informed consent and ethical clearance, 149 cases of hypertensive disorders of pregnancy were screened, and seven were lost to follow-up. Acute kidney injury was detected in 88 cases and acute renal failure in 30 cases of HDP. Thirty-one healthy pregnant nonhypertensive women were enrolled as controls. Quantitative measurement of serum NGAL levels was done by enzyme linked immunosorbent assay technique using a sandwich enzyme-linked immunosorbent assay kit. As per the Kidney Diseases Improving Global Outcomes International guidelines acute kidney injury network (AKIN), 50 cases (42.37%) of AKI stage I, 38 (32.2%) cases of AKI stage II, and 30 (25.42%) cases of renal failure were detected. Serum NGAL had a positive association with increasing proteinuria. It also had a positive correlation with systolic blood pressure (r∼0.36), diastolic blood pressure (r∼0.37), and serum creatinine (r∼0.4). NGAL was found to be significantly correlated with creatinine in the cases with the value of the correlation coefficient being 0.4. This direct correlation might be a consequence of endothelial dysfunction on which hypertension and proteinuria probably depends.

  1. No increase in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion following intravenous contrast enhanced-CT

    Energy Technology Data Exchange (ETDEWEB)

    Kooiman, Judith [Leiden University Medical Center, Department of Thrombosis and Haemostasis, Leiden (Netherlands); Leiden University Medical Center, Department of Nephrology, Leiden (Netherlands); Peppel, Wilke R. van de; Huisman, Menno V. [Leiden University Medical Center, Department of Thrombosis and Haemostasis, Leiden (Netherlands); Sijpkens, Yvo W.J. [Bronovo Hospital, Department of Nephrology, The Hague (Netherlands); Brulez, Harald F.H. [Sint Lucas Andreas Hospital, Department of Nephrology, Amsterdam (Netherlands); Vries, P.M. de [St. Antonius Hospital, Department of Vascular Surgery, Nieuwegein (Netherlands); Nicolaie, Mioara A.; Putter, H. [Leiden University Medical Center, Department of Medical Statistics and Bioinformatics, Leiden (Netherlands); Kooij, W. van der; Kooten, Cees van; Rabelink, Ton J. [Leiden University Medical Center, Department of Nephrology, Leiden (Netherlands)

    2015-07-15

    To analyze kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (N-GAL) excretion post-intravenous contrast enhanced-CT (CE-CT) in patients with chronic kidney disease (CKD). Patients were enrolled in a trial on hydration regimes to prevent contrast-induced acute kidney injury (CI-AKI). Blood and urine samples were taken at baseline, 4 - 6, and 48 - 96 h post CE-CT. Urinary KIM-1 and N-GAL values were normalized for urinary creatinine levels, presented as medians with 2.5 - 97.5 percentiles. Of the enrolled 511 patients, 10 (2 %) were lost to follow-up. CI-AKI occurred in 3.9 % of patients (20/501). Median KIM-1 values were 1.2 (0.1 - 7.7) at baseline, 1.3 (0.1 - 8.6) at 4 - 6 h, and 1.3 ng/mg (0.1 - 8.1) at 48 - 96 h post CE-CT (P = 0.39). Median N-GAL values were 41.0 (4.4 - 3,174.4), 48.9 (5.7 - 3,406.1), and 37.8 μg/mg (3.5 - 3,200.4), respectively (P = 0.07). The amount of KIM-1 and N-GAL excretion in follow-up was similar for patients with and without CI-AKI (P-value KIM-1 0.08, P-value N-GAL 0.73). Neither patient characteristics at baseline including severe CKD, medication use, nor contrast dose were associated with increased excretion of KIM-1 or N-GAL during follow-up. KIM-1 and N-GAL excretion were unaffected by CE-CT both in patients with and without CI-AKI, suggesting that CI-AKI was not accompanied by tubular injury. (orig.)

  2. Low Serum Neutrophil Gelatinase-associated Lipocalin Level as a Marker of Malnutrition in Maintenance Hemodialysis Patients.

    Directory of Open Access Journals (Sweden)

    Hirotaka Imamaki

    Full Text Available Neutrophil gelatinase-associated lipocalin (NGAL or LCN2 is an iron-transporting factor which possesses various activities such as amelioration of kidney injury and host defense against pathogens. Its circulating concentrations are elevated in acute and chronic kidney diseases and show a positive correlation with poor renal outcome and mortality, but its clinical significance in maintenance hemodialysis (HD patients remains elusive.Serum NGAL levels were determined by enzyme-linked immunosorbent assay in out-patient, Japanese HD subjects. Their correlation to laboratory findings and morbidity (as development of severe infection or serum albumin reduction was investigated using linear regression analysis and χ2 test.Pre-dialysis serum NGAL levels in HD patients were elevated by 13-fold compared to healthy subjects (n=8, P<0.001. In a cross-sectional study of 139 cases, serum NGAL concentrations were determined independently by % creatinine generation rate (an indicator of muscle mass, standardized coefficient β=0.40, P<0.001, peripheral blood neutrophil count (β=0.38, P<0.001 and anion gap (which likely reflects dietary protein intake, β=0.16, P<0.05. Iron administration to anemic HD patients caused marked elevation of peripheral blood hemoglobin, serum ferritin and iron-regulatory hormone hepcidin-25 levels, but NGAL levels were not affected. In a prospective study of 87 cases, increase in serum albumin levels a year later was positively associated to baseline NGAL levels by univariate analysis (r=0.36, P<0.01. Furthermore, within a year, patients with the lowest NGAL tertile showed significantly increased risk for marked decline in serum albumin levels (≥0.4 g/dl; odds ratio 5.5, 95% confidence interval 1.5-20.3, P<0.05 and tendency of increased occurrence of severe infection requiring admission (odds ratio 3.1, not significant compared to the middle and highest tertiles.Low serum NGAL levels appear to be associated with current

  3. A comparison of neutrophil gelatinase-associated lipocalin and immature to total neutrophil ratio for diagnosing early-onset neonatal sepsis

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    Rocky Wilar

    2016-07-01

    Full Text Available Background Neonatal sepsis is a clinical syndrome caused by the invasion of microorganisms into the bloodstream. Early diagnosis of early-onset neonatal sepsis (EONS is difficult. Laboratory tests with high sensitivity and specificity are needed in order to make early diagnoses in newborns.Objective To compare the sensitivity and specificity of neutrophil gelatinase-associated lipocalin (NGAL and immature to total (IT neutrophil ratio for the diagnosis of early-onset neonatal sepsis.Methods This observational study with cross-sectional design was conducted in the Neonatology Division, Prof. R. D. Kandou General Hospital from November 2012 to April 2014. Consecutive sampling was applied. There were 103 newborns with suspected EONS who fulfilled the inclusion criteria. Complete blood counts, blood cultures, as well as NGAL and IT ratio measurements were performed.Results NGAL was not significantly more sensitive than IT ratio [80.4% vs. 67.3%, respectively; (P=0.058]. However, NGAL had lower specificity than IT ratio (27.7% vs. 50.0%, respectively; P=0.016. The positive predictive values (57.0% vs. 64.9%, respectively; P=0.176, and negative predictive values (54.2% vs. 52.6%, respectively; P=0.451 were similar in both diagnostic tests.Conclusion Immature to total neutrophil (IT ratio has higher specificity compared to NGAL for early diagnosis of EONS. However, the difference in sensitivity between the two test is not statistically significant.

  4. Neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in children after cardiac surgery

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    Meta Herdiana Hanindita

    2016-08-01

    Full Text Available Background Acute kidney injury (AKI is still diagnosed by measuring the estimated creatinine clearance (eCCl, despite the fact that it may not change until 50% or more of kidney function has been lost. AKI after cardiac surgery is related to prolonged intensive care, decreased quality of life, and increased long term mortality. Neutrophil gelatinase-associated lipocalin (NGAL represents an early biomarker of AKI, which may be useful for assessing AKI in cardiac patients. Objective To determine the validity of urinary and plasma NGAL as biomarkers for AKI in children after cardiac surgery. Methods Subjects were children who underwent cardiac surgery in Dr. Soetomo Hospital, Surabaya, Indonesia from August 2013 to January 2014. Serial urine and blood samples were analyzed for NGAL before surgery, as well as at 2h, 4h, 12h, and 24h after surgery. The AKI was established based on pRIFLE criteria. Estimated creatinine clearance (eCCl was calculated from the estimated glomerular filtration rate (eGFR, according to age by the traditional Schwartz formula. Serum creatinine was assayed by the Jaffe method before surgery, as well as at 12h, 24h, 48h, and 72h after surgery. Results Of 20 subjects, 5 developed AKI. Urinary and plasma NGAL increased markedly at 2h postoperatively, as compared to eGFR which showed a rise at 12-48 h after cardiac surgery. Analysis of 2h post-operative urinary NGAL at a cut off value of 11.270ng/mL yielded an area under the curve (AUC of 1.00 (95%CI 2.63 to 12.13, with sensitivity and specificity of 100% each for AKI. In addition, 2h post-operative plasma NGAL at a cut off value of 8.385 ng/mL yielded an AUC of 1.00 (95%CI 3.71 to 12.15 with sensitivity and specificity of 100% each for AKI. Conclusion Urinary and plasma NGAL are valid as early biomarkers for AKI in children after cardiac surgery.

  5. Neutrophil gelatinase-associated lipocalin and albuminuria as predictors of acute kidney injury in patients treated with goal-directed haemodynamic therapy after major abdominal surgery.

    LENUS (Irish Health Repository)

    Cullen, Mr

    2013-10-11

    Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a new biomarker for the early identification of acute kidney injury (AKI). There is also increasing evidence of an association between urinary albumin\\/creatinine ratio (ACR) and AKI. The primary aim of this study was to evaluate the clinical utility of these biomarkers to predict AKI in a population of perioperative patients treated with goal-directed haemodynamic therapy (GDHT). Secondary aims were to examine NGAL and ACR as sensitive biomarkers to detect the effects of GDHT and to investigate the association of these biomarkers with secondary outcomes.

  6. Urinary Neutrophil Gelatinase-Associated Lipocalin and Progression of Diabetic Nephropathy in Type 1 Diabetic Patients in a Four-Year Follow-Up Study

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Hansen, Henrik Post; Jensen, Berit Ruud

    2010-01-01

    Background: Neutrophil gelatinase-associated lipocalin (NGAL), a marker of renal tubular damage, predicts progression in non-diabetic chronic kidney. We evaluated urinary (u)-NGAL as a predictor of progression in diabetic nephropathy in type 1 diabetic (T1D) patients. Methods: As a substudy of a 4......-year randomized, intervention study evaluating low-protein diet in T1D patients with diabetic nephropathy, 78 patients were studied with yearly measurements of u-NGAL (ELISA, BioPorto). Outcome: Decline in glomerular filtration rate (GFR) ((51)Cr-EDTA), and end-stage renal disease (ESRD) or death...

  7. Analyis of changes in the serum concentration of cystatin c, creatinine and renal neutrophil gelatinase-associated lipocalin in patients with hemorrhagic fever with renal syndrome

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    E. M. Mingazova

    2015-01-01

    Full Text Available Introduction. Acute kidney injury is a frequent complication of hemorrhagic fever with renal syndrome. The objective evaluation of аcute kidney injury severity degree is significant in determining the amount of medical actions at hemorrhagic fever with renal syndrome.Objective. Тhe shifts of acute kidney injury biomarkers’ levels (urine neutrophil gelatinase-associated lipocalin, serum cystatin C and serum creatinine at different periods of hemorrhagic fever with renal syndrome were evaluated.Methods. Depending to hemorrhagic fever with renal syndrome severity the patients were divided into groups with severe (n=16 and moderate form of hemorrhagic fever with renal syndrome (n=10; the control group included 10 healthy individuals. The levels of biomarkers were measured by ELISA.Results. Тhe serum concentration of creatinine and cystatin C – markers of glomerular pathology – increased significantly in hemorrhagic fever with renal syndrome, peaking at oligouric period; while changes of cystatin C were more rapid. Urine neutrophil gelatinase-associated lipocalin level – marker of renal tubular damage – increased 30 to 96 times compared to the control group in fever period of hemorrhagic fever with renal syndrome and gradually decreased thereafter.Conclusion. Тhe use of modern biochemical markers of renal pathology (sCystatin C, urine neutrophil gelatinaseassociated lipocalin in hemorrhagic fever with renal syndrome, along with traditional indicators, allows a more differentiated approach to the assessment of renal pathology and gives additional evidence to highlight stage and severity of the disease.

  8. Predict value of monitoring changes of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after coronary angiography and percutaneous coronary intervention on early diagnosis of contrast-induced nephropathy

    Institute of Scientific and Technical Information of China (English)

    王磊

    2014-01-01

    Objective To explore the predict value of monitoring changes of urinary neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(KIM-1)after coronary angiography(CAG)and percutaneous coronary intervention(PCI)on the early diagnosis of contrast-induced nephropathy(CIN).Methods One hundred and sixty patients underwent CAG and PCI were en-

  9. Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta

    DEFF Research Database (Denmark)

    Karlsen, Joachim R; Borregaard, Niels; Cowland, Jack B

    2010-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL) is a siderophore-binding antimicrobial protein that is up-regulated in epithelial tissues during inflammation. We demonstrated previously that the gene encoding NGAL (LCN2) is strongly up-regulated by interleukin (IL)-1beta in an NF-kappaB-depende...

  10. Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard

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    Majid Ebrahimi

    2010-01-01

    Full Text Available Sulfur mustard (SM is a potent vesicant that has been employed as a chemical weapon in various conflicts during the 20th century. More recently, mustard was used in the Iraq conflict against Iranian troops and civilians. At the present time there are more than 40.000 people suffering from pulmonary lesions special bronchiolitis obliterans (BOs due to mustard gas. SM increases the endogenous production of reactive oxygen species (ROS. Neutrophil Gelatinase-associated Lipocalin 2 (Lcn2, NGAL is a member of the lipocalin superfamily for which a variety of functions such as cellular protection against oxidative stress have been reported. Ten normal and Twenty SM-induced COPD patient individuals were studied. Assessment of NGAL expressions in healthy and the patients endobrinchial biopsies were performed by semiquantitative RT-PCR, real-time RT-PCR, and Immunohistochemistry analysis. While Normal control samples expressed same level of mRNA NGAL, expression level of mRNA-NGAL was upregulated about 1.4- to 9.8-folds compared to normal samples. No significant immunoreactivity was revealed in both samples. As we are aware this is the first report of induction of NGAL in patients exposed to SM. NGAL may play an important role in cellular protection against oxidative stress toxicity induced by mustard gas in airway wall of patients.

  11. Increased Neutrophil Gelatinase-Associated Lipocalin is Associated with Mortality and Multiple Organ Dysfunction Syndrome in Severe Sepsis and Septic Shock.

    Science.gov (United States)

    Wang, Biao; Chen, Gang; Zhang, Jun; Xue, Jiping; Cao, Yifei; Wu, Yunfu

    2015-09-01

    This study examines the clinical utility of increased neutrophil gelatinase-associated lipocalin (NGAL) as an indicator of mortality and multiple organ dysfunction syndrome (MODS) in severe sepsis and septic shock. We designed a prospective cohort study in an intensive care unit, and 123 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between NGAL and the development of MODS and mortality. These associations were determined by the Mann-Whitney U test, log-rank test, Cox proportional hazards regression analyses, and plotting the receiver operating characteristic curve. Patients with high NGAL (75th percentile) had increased risk of mortality and MODS compared with patients with low NGAL (log-rank test, P MODS on day 1, and 37 patients (30%) on day 7. The area under the receiver operating characteristic curve showed that high NGAL could predict mortality (0.6385) during intensive care unit stay. After adjustment for confounding risk factors chosen by backward elimination by Cox regression analysis, high NGAL remained an independent predictor of mortality and MODS (hazard ratios, 2.128 [95% confidence interval, 1.078-4.203; P = 0.030] and 1.896 [95% confidence interval, 1.012-3.552; P = 0.046], respectively). High plasma NGAL independently predicts mortality and MODS in severe sepsis and septic shock.

  12. The Predictivity of Neutrophil Gelatinase Associated Lipocaline in the Development of Radiocontrast-Induced Nephropathy in the Intensive Care Unit Patients

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    Funda TÜRKMEN

    2013-05-01

    Full Text Available OBJECTIVE: The aim of this study is to investigate the predictive value of neutrophil gelatinase associated lipocaline (NGAL levels in the development of radiocontrast-induced nephropathy (rin in intensive care unit patients. MATERIAL and METHODS: Forty patients (female: male was 23:17 with a mean age of 73.7± 9.7 yrs (range= 60-94 yrs were included in the study. Lopromide 623mg/dl (ultravist 300 (iv was administered at a dose of 1.5 ml/kg. NGAL measurements were performed with the ELISA method on serum samples (cut-off >25 ng/ml. RESULTS: Eight patients were diagnosed as RIN. Five of these had 20% or more increases in NGAL levels. Cases who developed RIN had a statistically significant and direct correlation between the increases in NGAL and serum creatinine levels (p= 0.02. When the means of NGAL levels were compared before and six hours after the procedure, there was a significant increase after the procedure (p0.05. CONCLUSION: When compared to creatinine, plasma NGAL levels help to establish the diagnosis of RIN at a much earlier stage.

  13. Plasma neutrophil gelatinase-associated lipocalin as a marker for the prediction of worsening renal function in children hospitalized for acute heart failure.

    Science.gov (United States)

    Elsharawy, Sahar; Raslan, Lila; Morsy, Saed; Hassan, Basheir; Khalifa, Naglaa

    2016-01-01

    Acute heart failure (AHF) is frequently associated with worsening renal function in adult patients. Neutrophil gelatinase-associated lipocalin (NGAL) serves as an early marker for acute renal tubular injury. To assess the role of plasma NGAL in predicting worsening renal function (WRF) in children with AHF, we studied 30 children hospitalized for AHF; children with history of chronic renal disease or on nephrotoxic drugs were excluded. Twenty age- and sex-matched healthy children were included in the study as a control group. Echocardiographic examination was performed on admission. Blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR) and plasma NGAL levels were measured on admission and 72 h later. Seventeen (56.6%) patients developed WRF within the three-day follow-up period. At presentation, plasma NGAL level was significantly elevated in children who developed WRF. Admission plasma NGAL level correlated with renal parameters (BUN, creatinine and eGFR) as well as with left ventricular systolic parameters (ejection fraction and fractional shortening). For prediction of WRF, admission plasma, NGAL level>27.5 μg/L had sensitivity and specificity of 90% and 68%, respectively. The area under the receiver-operator curve was higher for NGAL (0.869) than for BUN (0.569) or eGFR (0.684). We conclude that admission plasma NGAL level can predict WRF in children hospitalized for AHF.

  14. Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein.

    Science.gov (United States)

    Asada, Toshifumi; Isshiki, Rei; Hayase, Naoki; Sumida, Maki; Inokuchi, Ryota; Noiri, Eisei; Nangaku, Masaomi; Yahagi, Naoki; Doi, Kent

    2016-01-01

    Application of acute kidney injury (AKI) biomarkers with consideration of nonrenal conditions and systemic severity has not been sufficiently determined. Herein, urinary neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid-binding protein (L-FABP) and nonrenal disorders, including inflammation, hypoperfusion and liver dysfunction, were evaluated in 249 critically ill patients treated at our intensive care unit. Distinct characteristics of NGAL and L-FABP were revealed using principal component analysis: NGAL showed linear correlations with inflammatory markers (white blood cell count and C-reactive protein), whereas L-FABP showed linear correlations with hypoperfusion and hepatic injury markers (lactate, liver transaminases and bilirubin). We thus developed a new algorithm by combining urinary NGAL and L-FABP with stratification by the Acute Physiology and Chronic Health Evaluation score, presence of sepsis and blood lactate levels to improve their AKI predictive performance, which showed a significantly better area under the receiver operating characteristic curve [AUC-ROC 0.940; 95% confidential interval (CI) 0.793-0.985] than that under NGAL alone (AUC-ROC 0.858, 95% CI 0.741-0.927, P = 0.03) or L-FABP alone (AUC-ROC 0.837, 95% CI 0.697-0.920, P = 0.007) and indicated that nonrenal conditions and systemic severity should be considered for improved AKI prediction by NGAL and L-FABP as biomarkers.

  15. Serum neutrophil gelatinase-associated lipocalin concentration reflects severity of coronary artery disease in patients without heart failure and chronic kidney disease.

    Science.gov (United States)

    Katagiri, Mikako; Takahashi, Masao; Doi, Kent; Myojo, Masahiro; Kiyosue, Arihiro; Ando, Jiro; Hirata, Yasunobu; Komuro, Issei

    2016-10-01

    Serum neutrophil gelatinase-associated lipocalin (NGAL) is recognized as a useful biomarker for acute kidney injury. Recently, elevated NGAL levels were reported in patients with heart failure and cardiac events, but the association between serum NGAL and severity of coronary artery disease (CAD) has not been investigated adequately. This study aimed to evaluate the association between serum NGAL concentration and CAD severity in patients without heart failure and chronic kidney disease. Two-hundred thirteen patients [mean age: 66.2 ± 9.2 (SD)] without heart failure and chronic kidney disease (estimated glomerular filtration rate >60 mL/min/1.73 m(2)) who underwent coronary angiography were retrospectively analyzed using the SYNTAX score. The mean concentration of serum NGAL was 134.3 ± 111.3 ng/mL. A statistically significant correlation was observed between serum NGAL levels and the SYNTAX score (R = 0.18, P = 0.0091). Multivariable analysis also showed elevated serum NGAL as an independent risk factor for a high SYNTAX score (P 100 ng/mL) and high levels of BNP (>25 pg/mL) had a higher SYNTAX score (low-low vs. high-high: 13.8 ± 13.4 vs. 20.8 ± 18.9, P heart failure. Serum NGAL might be a biomarker for CAD severity.

  16. The expression and significance of matrix metalloproteinases and neutrophil gelatinase-associated lipocalin in serum and placental tissue of preeclampsia maternal%子痫前期患者血清基质金属蛋白酶-9、中性粒细胞明胶酶相关脂质运载蛋白水平及其在胎盘组织中的表达

    Institute of Scientific and Technical Information of China (English)

    王卉

    2013-01-01

    目的 探讨子痫前期患者血清基质金属蛋白酶-9(MMP-9)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平及其在胎盘组织中的表达变化.方法 74例子痫前期患者作为研究对象,其中重度39例、轻度35例;同时选取正常足月妊娠产妇30例作为对照组,应用酶联免疫吸附法测定三组血清MMP-9、NGAL水平,应用RT-PCR测定三组胎盘组织中MMP-9mRNA及NGALmRNA水平.结果 轻度子痫前期组、重度子痫前期组血清MMP-9、NGAL水平均明显高于对照组(t=3.127、2.846、3.508、3.284,均P<0.05),胎盘组织中MMP-9 mRNA、NGAL mRNA水平均明显低于对照组(t=-2.842、-2.728、-3.532、-3.276,均P<0.05);重度子痫前期患者血清MMP-9、NGAL水平显著高于轻度子痫前期患者(t=2.732、2.741,均P<0.05),重度子痫前期组胎盘组织中MMP-9 mRNA、NGAL mRNA水平明显低于轻度子痫前期组(t=-2.681、-2.587,均P<0.05);子痫前期血清MMP-9水平与NGAL水平呈正相关(r=0.606,P<0.05),胎盘组织中MMP-9 mRNA表达水平与NGAL mRNA表达水平呈正相关(r=0.532,P<0.05).结论 子痫前期患者血清MMP-9、NGAL水平显著升高,胎盘组织MMP-9 mRNA、NGAL mRNA水平显著下降,提示两者可能参与子痫的发病过程.%Objective To investigate expression and significance of matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL) in serum and placental tissue of preeclampsia maternal.Methods 74 cases of preeclampsia pregnant women as research subjects,which 39 cases of severe preeclampsia,35 cases of mild preeclampsia,selected 30 cases of normal late maternal as the control group.Three groups of maternal serum levels of MMP-9 and of NGAL were detected by enzyme-linked immunosorbent assay.RT-PCR was used to test placenta MMP-9 mRNA,and NGAL mRNA level.Results Preeclampsia maternal serum levels of MMP-9 and NGAL level were significantly higher than those of severe preeclampsia pregnant women serum

  17. Urinary neutrophil gelatinase-associated lipocalin and cystatin C compared to the estimated glomerular filtration rate to predict risk in patients with suspected acute myocardial infarction.

    Science.gov (United States)

    von Jeinsen, Beatrice; Kraus, Daniel; Palapies, Lars; Tzikas, Stergios; Zeller, Tanja; Schauer, Anne; Drechsler, Christiane; Bickel, Christoph; Baldus, Stephan; Lackner, Karl J; Münzel, Thomas; Blankenberg, Stefan; Zeiher, Andreas M; Keller, Till

    2017-10-15

    Impaired renal function, reflected by estimated glomerular filtration rate (eGFR) or cystatin C, is a strong risk predictor in the presence of acute myocardial infarction (AMI). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of acute kidney injury. uNGAL might also be a good predictor of outcome in patients with cardiovascular disease. Aim of the present study was to evaluate the prognostic value of uNGAL compared to eGFR and cystatin C in patients with suspected AMI. 1818 patients were enrolled with suspected AMI. Follow-up information on the combined endpoint of death or non-fatal myocardial infarction was obtained 6months after enrolment and was available in 1804 patients. 63 events (3.5%) were registered. While cystatin C and eGFR were strong risk predictors for the primary endpoint even adjusted for several variables, uNGAL was not independently associated with outcome: When applied continuously uNGAL was associated with outcome but did not remain a statistically significant predictor after several adjustments (i.e. eGFR). By adding cystatin C or uNGAL to GRACE risk score variables, only cystatin C could improve the predictive value while uNGAL showed no improvement. We could show that cystatin C is an independent risk predictor in patients with suspected AMI and cystatin C can add improvement to the commonly used GRACE risk score. In contrast uNGAL is not independently associated with outcome and seems not to add further prognostic information to GRACE risk score. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Decreased circulating 25-(OH) Vitamin D concentrations in obese female children and adolescents: positive associations with Retinol Binding Protein-4 and Neutrophil Gelatinase-associated Lipocalin.

    Science.gov (United States)

    Metheniti, Dimitra; Sakka, Sophia; Dracopoulou, Maria; Margeli, Alexandra; Papassotiriou, Ioannis; Kanaka-Gantenbein, Christina; Chrousos, George P; Pervanidou, Panagiota

    2013-01-01

    Hypovitaminosis D has been associated with adult as well as childhood obesity. Retinol-binding-protein-4 (RBP-4) and Neutrophil Gelatinase-associated Lipocalin (NGAL) are altered in obese individuals. The aim of this study was to examine circulating 25-(OH) Vitamin D (25-(OH) D) concentrations according to BMI and its associations with RBP-4 and NGAL in female children and adolescents. Seventy-nine (79) children, aged 8-16 years, were studied and divided into four groups: 19 control (BMI z-score range -2.15 - 1.24), 20 overweight (1.34 - 2.49), 20 obese (2.50 - 2.87) and 20 ultra-obese (3 - 4.37). Patients were derived from a Pediatric Obesity Clinic. Plasma 25-(OH) D, RBP-4 and NGAL concentrations were measured with specific assays. Plasma 25-(OH) D concentrations were decreased significantly in the ultra-obese (p=0.005) and marginally in the obese group (p=0.05) compared to the control group. In the entire BMI range, Spearman correlations revealed strong positive associations between 25-(OH) D and RBP-4 (r=0.349, p=0.002) and between 25-(OH) D and NGAL (r=0.338, p=0.003). 25-(OH) D is deficient in a clinical population of obese female children and adolescents, whereas in the entire BMI range 25-(OH) D is associated with RBP4 and NGAL concentrations. Longitudinal studies are needed to reveal the role of these associations in metabolic alterations related to childhood and adolescent obesity and associated metabolic morbidities.

  19. Diagnostic and prognostic value of neutrophil gelatinase associated lipocalin and cancer antigen 15-3 serum levels in benign and malignant breast disease

    Directory of Open Access Journals (Sweden)

    Tunc Eren

    2016-03-01

    Full Text Available Purpose: Increased neutrophil gelatinase-associated lipocalin (NGAL serum levels have been shown in studies for colorectal, gastric, esophageal, liver, thyroid and lung cancer. The aim of this study was to demonstrate the differences of NGAL and cancer antigen 15-3 (CA15-3 serum levels between the groups of patients diagnosed with either breast cancer, or benign breast disorders in order to investigate the diagnostic and prognostic value of these biomarkers. Material and Methods: The patients were divided into three groups as the malignancy group, the benign group, and the control group. Serum NGAL/CA15-3 levels, the presence of a breast lesion, and the type of the lesion were recorded. In the malignancy group; parameters including tumor type, invasion degree, T/N stages, lymphovascular/perineural invasion, histological grade, c-erbB2, e-cadherin, estrogen and progesteron reseptor levels were recorded, and compared between the three groups. Results: Eighty four patients were enrolled to the study. The mean NGAL level was higher in the benign group. CA15-3 detection did not reveal significant difference between the study groups. In the malignant group; increased serum NGAL levels were associated with higher histological grade, while elevated CA15-3 levels were associated with positive lymph node count. Conclusion: The association of elevated CA15-3 levels with metastatic lymph node counts proves that the prognostic value of this marker is higher than its diagnostic accuracy. On the other hand, serum NGAL detection results reveal that the diagnostic value of NGAL for breast cancer is lower when compared to other cancer types. [Cukurova Med J 2016; 41(1.000: 87-96

  20. The changes of neutrophil gelatinase-associated lipocalin in plasma and its expression in adipose tissue in pregnant women with gestational diabetes.

    Science.gov (United States)

    Lou, Yanqin; Wu, Chaoying; Wu, Min; Xie, Cui; Ren, Lirong

    2014-04-01

    To investigate plasma levels and the expression of neutrophil gelatinase-associated lipocalin (NGAL) in subcutaneous adipose tissue (SAT) in patients with gestational diabetes mellitus (GDM). The study recruited 260 Chinese women divided into three groups: 96 were healthy pregnant women with pre-pregnancy body mass index (pre-pregnancy BMI) below 25kg/m(2) (GROUP 1), 84 were women with GDM with pre-pregnancy BMI below 25kg/m(2) (GROUP 2) and 80 were women with GDM with pre-pregnancy BMI over 25kg/m(2) (GROUP 3). Laboratory and anthropometric measurements were recorded and NGAL plasma levels were determined by ELISA for subjects in all groups. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of NGAL and tumor necrosis factor-α (TNF-α) in SAT (30 cases in each group). Our results demonstrated statistically significant elevation in plasma NGAL concentrations in GROUP 2 and GROUP 3 compared with GROUP 1 (p<0.001 for both group comparisons). Moreover, SAT NGAL mRNA (p<0.001 and p<0.001, respectively) and protein (p<0.001 and p<0.001, respectively) expression levels were higher in GROUP 3 than in both GROUP 1 and GROUP 2. Correlations were noted between the plasma NGAL concentration and various parameters of insulin resistance. Plasma NGAL may play a role in the development of insulin resistance in GDM, and the high levels of NGAL expression in SAT in overweight women with GDM suggests that NGAL in SAT is associated with obesity in women with GDM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Correlation of plasma osteopontin and neutrophil gelatinase-associated lipocalin levels with the severity and clinical outcome of pelvic inflammatory disease.

    Science.gov (United States)

    Tee, Yi-Torng; Wang, Po-Hui; Yang, Shun-Fa; Tsai, Hsiu-Ting; Lee, Shu-Kuei; Ko, Jiunn-Liang; Lin, Long-Yau; Chen, Shiuan-Chih

    2014-06-01

    To investigate the correlation of two important inflammatory biomarkers, plasma osteopontin and neutrophil gelatinase-associated lipocalin (NGAL), with the severity and outcome of pelvic inflammatory disease (PID). Sixty-one patients with PID, including 25 patients with tubo-ovarian abscess (TOA), were consecutively recruited. Their blood samples were tested for the concentrations of plasma osteopontin and NGAL using enzyme-linked immunosorbent assay. The associations of these biomarkers with TOA, length of hospitalization, and incidence of surgery were also analyzed. Plasma osteopontin level was significantly increased in PID patients with TOA compared to PID patients without TOA (median 107.77 ng/mL vs. 72.39 ng/mL, p = 0.004). However, there was no significant difference for plasma NGAL. If the cutoff level of plasma osteopontin was set at 81.1 ng/mL, there was a 76.0% sensitivity and a 24.0% false negative rate in predicting TOA in PID patients. Plasma osteopontin significantly correlated with length of hospital stay (r = 0.467, p < 0.001), and this correlation was better than that of NGAL. However, neither biomarker was associated with incidence of surgery. Plasma osteopontin has a better correlation with TOA and length of hospitalization compared to NGAL. If plasma osteopontin level falls below 81.1 ng/mL, PID patients will have about a 20% chance of developing TOA. Incorporating plasma osteopontin, but not NGAL, will allow for an adjuvant diagnostic biomarker for TOA and predictor of length of hospital stay. Copyright © 2014. Published by Elsevier B.V.

  2. Early predictors of acute kidney injury in patients with cirrhosis and bacterial infection: urinary neutrophil gelatinase-associated lipocalin and cardiac output as reliable tools

    Science.gov (United States)

    Ximenes, Rafael O.; Farias, Alberto Q.; Helou, Claudia M.B.

    2015-01-01

    Background Hemodynamic abnormalities and acute kidney injury (AKI) are often present in infected cirrhotic patients. Hence, an early diagnosis of AKI is necessary, which might require the validation of new predictors as the determinations of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and cardiac output. Methods We evaluated 18 infected cirrhotic patients subdivided into two groups at admission (0 hours). In Group I, we collected urine samples at 0 hours, 6 hours, 24 hours, and 48 hours for uNGAL and fractional excretion of sodium determinations. In Group II, we measured cardiac output using echocardiography. Results The age of patients was 55.0±1.9 years, and 11 patients were males. The Model for End-Stage Liver Disease score was 21±1, whereas the Child–Pugh score was C in 11 patients and B in 7 patients. Both patients in Group I and Group II showed similar baseline characteristics. In Group I, we diagnosed AKI in 5 of 9 patients, and the mean time to this diagnosis by measuring serum creatinine was 5.4 days. Patients with AKI showed higher uNGAL levels than those without AKI from 6 hours to 48 hours. The best accuracy using the cutoff values of 68 ng uNGAL/mg creatinine was achieved at 48 hours when we distinguished patients with and without AKI in all cases. In Group II, we diagnosed AKI in 4 of 9 patients, and cardiac output was significantly higher in patients who developed AKI at 0 hours. Conclusion Both uNGAL and cardiac output determinations allow the prediction of AKI in infected cirrhotic patients earlier than increments in serum creatinine. PMID:26484038

  3. Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study

    Science.gov (United States)

    Liu, Kathleen D.; Yang, Wei; Go, Alan S.; Anderson, Amanda H.; Feldman, Harold I.; Fischer, Michael J.; He, Jiang; Kallem, Radhakrishna R.; Kusek, John W.; Master, Stephen R.; Miller, Edgar R.; Rosas, Sylvia E.; Steigerwalt, Susan; Tao, Kaixiang; Weir, Matthew R.; Hsu, Chi-yuan

    2015-01-01

    Background Chronic kidney disease is common and associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration—based markers (such as serum creatinine or albuminuria). Study Design Cohort study, Chronic Renal Insufficiency Cohort (CRIC) Study. Setting & Participants 3386 participants with estimated glomerular filtration rate of 20-70 mL/min/1.73 m2 enrolled from June 2003 through August 2008. Predictor Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Outcomes Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke or peripheral artery disease) and death through March 2011. Measurements Urine NGAL concentration measured at baseline with a two-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). Results There were 428 heart failure events (during 16383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16584 person-years of follow-up) and 522 deaths (during 18214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors and cardiac medications, higher urine NGAL levels remained independently associated with ischemic atherosclerotic events (adjusted HR for the highest [>49.5 ng/ml] vs. lowest [≤6.9 ng/ml] quintile, 1.83 [95% CI, 1.20-2.81]; HR, per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Limitations Urine NGAL was measured only once. Conclusions Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were independently associated with future ischemic atherosclerotic

  4. A comparison of neutrophil gelatinase-associated lipocalin and immature to total neutrophil ratio for diagnosing early-onset neonatal sepsis

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    Rocky Wilar

    2016-07-01

    Conclusion Immature to total neutrophil (IT ratio has higher specificity compared to NGAL for early diagnosis of EONS. However, the difference in sensitivity between the two test is not statistically significant.

  5. Expression and significance of neutrophil gelatinase-associated lipocalin in renal interstitial fibrosis in rats%NGAL在大鼠肾间质纤维化中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    张桦; 朱晔; 贾宁; 张慧涛; 郑晶; 朱伟平; 周文英; 林宇静; 王晓鸿

    2012-01-01

    目的 探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在肾间质纤维化(RIF)中的表达变化及其意义.方法 60只SD雄性大鼠随机分为假手术(SOR)组、单侧输尿管梗阻(UUO)组和血管紧张素转换酶抑制剂(ACEI)组.ELISA法检测血清NGAL、肿瘤坏死因子(TNF)-α含量,免疫组化法检测肾组织NGAL、转化生长因子(TGF)-β1、基质金属蛋白酶-9(MMP-9)的表达水平.结果 (1)UUO组大鼠血清NGAL、TNF-α水平均显著高于ACEI组和SOR组[NGAL:( 69.2±5.6) pg/ml比(41.0±10.4)pg/ml、( 10.8 ±3.8) pg/ml,TNF-α:( 116.2±9.2)ng/ml比(99.8±14.0) ng/ml、(29.2±5.7) ng/ml,均P<0.05],SOR组最低.(2)NGAL、TGF-β1、MMP-9在UUO组大鼠肾小管间质内表达明显增强;在ACEI组,TGF-β1表达量低于UUO组,而NGAL、MMP-9表达量在术后14 d内均少于UUO组,但在术后21和28 d其表达量高于UUO组.(3)相关关系:在UUO组,血清NGAL水平与TNF-α、血清肌酐呈显著正相关(r=0.910、0.673,P<0.01);肾脏NGAL表达量与MMP-9表达水平呈显著正相关(r =0.913,P<0.01),与肾小管间质损伤指数、TGF-β1表达阳性程度在术后3~7d呈显著正相关(r=0.937、0.847,P<0.01),在术后14 ~ 28 d呈显著负相关(r=-0.945、-0.944,P<0.01).结论 NGAL在UUO大鼠血清与肾组织中的表达显著增加,并与MMP-9、TNF-α、TGF-β1等因子密切相关,而ACEI可通过多种机制影响NGAL在RIF中的生物学作用.%Objective To explore the expression and significance of neutrophil gelatina(s)e-associated lipocalin(NGAL)in renal interstitial fibrosis (RIF) in rats.Methods A total of 60 male Sprague-Dawley rats were randomly divided into 3 groups of sham operation (SOR),unilateral ureteral obstruction (UUO)and angiotensin-converting enzyme inhibitor (ACEI).The serum concentrations of NGAL and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA).And the expressions of NGAL,matrix metalloproteinase-9 (MMP-9) and

  6. Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: A prospective cohort study

    NARCIS (Netherlands)

    A.J.M. Zwiers (Alexandra); S.N. de Wildt (Saskia); J.M. van Rosmalen (Joost); Y.B. de Rijke (Yolanda); E.A.B. Buijs (Erik ); D. Tibboel (Dick); K. Cransberg (Karlien)

    2015-01-01

    textabstractIntroduction: Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase-associat

  7. Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: A prospective cohort study

    NARCIS (Netherlands)

    A.J.M. Zwiers (Alexandra); S.N. de Wildt (Saskia); J.M. van Rosmalen (Joost); Y.B. de Rijke (Yolanda); E.A.B. Buijs (Erik ); D. Tibboel (Dick); K. Cransberg (Karlien)

    2015-01-01

    markdownabstract#### Introduction Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase

  8. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    Science.gov (United States)

    Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

    2016-01-01

    Purpose To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. Methods This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Conclusion Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery. PMID:27143905

  9. Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

    Science.gov (United States)

    Marques, Francine Z; Prestes, Priscilla R; Byars, Sean G; Ritchie, Scott C; Würtz, Peter; Patel, Sheila K; Booth, Scott A; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P; Curl, Claire L; Bell, James R; Wai, Bryan; Srivastava, Piyush M; Kangas, Antti J; Soininen, Pasi; Ruohonen, Saku; Kähönen, Mika; Lehtimäki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E; Lewandowski, Paul A; Delbridge, Lea M; Burrell, Louise M; Inouye, Michael; Harrap, Stephen B; Charchar, Fadi J

    2017-06-14

    Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2-knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis-eQTL for LCN2 expression. Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  10. Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL may improve renal outcome of acute contrast media induced nephropathy: A randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study

    Directory of Open Access Journals (Sweden)

    Stiegler Philipp

    2011-08-01

    Full Text Available Abstract Background Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN. Neutrophil gelatinase-associated lipocalin (NGAL, a new biomarker predictive for acute kidney injury (AKI, has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. Methods/Design The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death. We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the

  11. Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL) may improve renal outcome of acute contrast media induced nephropathy: a randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study).

    Science.gov (United States)

    Schilcher, Gernot; Ribitsch, Werner; Otto, Ronald; Portugaller, Rupert H; Quehenberger, Franz; Truschnig-Wilders, Martini; Zweiker, Robert; Stiegler, Philipp; Brodmann, Marianne; Weinhandl, Klemens; Horina, Joerg H

    2011-08-17

    Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated lipocalin (NGAL), a new biomarker predictive for acute kidney injury (AKI), has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM) application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death.We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the treatment arm if 1200 patients are recruited into the

  12. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    Directory of Open Access Journals (Sweden)

    Guerrero-Orriach JL

    2016-04-01

    Full Text Available José Luis Guerrero-Orriach,1 Daniel Ariza-Villanueva,1 Ana Florez-Vela,1 Lourdes Garrido-Sánchez,2,3 María Isabel Moreno-Cortés,1 Manuel Galán-Ortega,1 Alicia Ramírez-Fernández,1 Juan Alcaide Torres,3 Concepción Santiago Fernandez,3 Isabel Navarro Arce,1 José María Melero-Tejedor,4 Manuel Rubio-Navarro,1 José Cruz-Mañas1 1Department of Cardio-Anaesthesiology, University Hospital Virgen de la Victoria, Málaga, Spain; 2CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN, Instituto de Salud Carlos III, Málaga, Spain; 3Department of Nutrition and Endocrinology, Instituto de Investigaciones Biomédicas de Málaga (IBIMA, University Hospital Virgen de la Victoria, Málaga, Spain; 4Department of Cardiovascular Surgery, University Hospital Virgen de la Victoria, Málaga, Spain Purpose: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL and neuronal enolase. Methods: This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results: After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL, neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng

  13. Accuracy of plasma and urine neutrophil gelatinase-associated lipocalin concentrations in predicting postoperative delirium in elderly patients%血浆和尿NGAL浓度预测老年患者术后谵妄的准确性

    Institute of Scientific and Technical Information of China (English)

    郝学超; 闵苏; 彭丽桦; 任力; 魏珂

    2016-01-01

    Objective To evaluate the accuracy of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) concentrations in predicting postoperative delirium in elderly patients.Methods From November 2014 to March 2015,70 patients of either sex who underwent total unilateral hip or knee replacement,aged 65-85 yr,with body mass index of 18-25 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,were selected.The Confusion Assessment Method for the Intensive Care Unit was used to assess the development of postoperative delirium at 24,48 and 72 h after operation.The patients were divided into either delirium group or non-delirium group according to whether or not postoperative delirium occurred.At 5 min before anesthesia induction,immediately after extubation,and at 24 and 72 h after operation,the midstream urine samples and peripheral venous blood samples were collected for determination of the urine and plasma NGAL concentrations by immuno-enhanced turbidimetry.At 5 min before anesthesia induction,and 24 and 48 h after operation,the serum creatinine and cystatin C concentrations were detected,and the development of postoperative acute kidney injury was recorded.The receiver operating characteristic curve for urine and plasma NGAL concentrations in diagnosing postoperative delirium was plotted,and the area under the curve and 95% confidence interval were calculated.The critical value and sensitivity and specificity were calculated according to the corresponding concentrations of NGAL in urine and plasma when Youden index reached the maximal value.Results The incidence of postoperative delirium was 15%.Compared with non-delirium group,the plasma NGAL concentrations were significantly increased immediately after extubation,and the urine NGAL concentrations were significantly increased immediately after extubation and at 24 h after operation in delirium group (P<0.01).There was no significant difference in the serum creatinine and cystatin C

  14. Implications of MMP9 for Blood Brain Barrier Disruption And Hemorrhagic Transformation Following Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Renee Jade Turner

    2016-03-01

    Full Text Available Numerous studies have documented increases in matrix metalloproteinases (MMPs, specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB, increased risk of hemorrhagic complications and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke.

  15. Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke

    Science.gov (United States)

    Turner, Renée J.; Sharp, Frank R.

    2016-01-01

    Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke. PMID:26973468

  16. Relationship between serum neutrophil gelatinase-associated lipocalin and iron metabolic index in preschool children%学龄前儿童血清中性粒细胞明胶酶相关脂质运载蛋白与铁代谢指标相关性及其意义

    Institute of Scientific and Technical Information of China (English)

    陈科; 程昕然; 章岚; 罗红裔; 高宁; 王劲; 傅桂英; 毛萌

    2012-01-01

    [目的]初步分析中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase associated lipocalin,NGAL)水平对铁代谢指标血红蛋白(hemoglobin,HB)、铁蛋白(serum ferritin,SF)、血清转铁蛋白受体(serum transferrin receptor,sTfR)、转铁蛋白/铁蛋白指数(transferritin receptor-ferritin index,TFR-F)以及机体铁含量(body iron content,BIC)的关系. [方法]随机抽取473名3~6岁(不足7岁)学龄前儿童纳入本研究,利用氰化高铁血红蛋白法测定HB、ELISA 法测定血清NGAL、SF及sTfR,并根据相关公式计算TRFI和BIC指数. [结果]血清NGAL与sTfR、TFR F和BIC均呈显著相关关系(偏相关系数r=0.23、0.24、-0.15,P<0.01或<0.05).贫血儿童血清NGAL水平显著低于非贫血儿童[(152.8±33.4)vs(220.7士25.4)pg/mL] (P<0.05);以指标中位数为界,低sTfR组儿童血清NGAL水平明显低于高sTfR组[(181.05±41.1)vs(257.6±47.8)pg/mL](P<0.05),低BIC组儿童血清NGAL水平明显高于高BIC组[(269.1±49.4)vs(181.3±30.8) pg/mL] (P<0.05).低NGAL组儿童血清sTfR水平及TFR-F指数显著低于高NGAL组(P<0.05),而HB、SF以及BIC组间差异无统计学意义(P>0.05). [结论] NGAL可能主要通过阻止红系统增殖参与调节儿童铁代谢稳态,而与机体铁储备过程无关.%[Objective] To explore the correlation of neutrophil gelatinase-associated lipocalin (NGAL) and iron metabolic index,including hemoglobin (HB),serum ferritin (SF), serum transferrin receptor (sTfR) , transferritin receptor-fer-ritin index (TFR-F) and body iron content (B1C). [Methods] About 473 preschool children with 2~7 years old were randomly selected from eight kindergartens,including 223 boys and 250 girls with (47. 8 ± 14. 5) months. HB was measured by HiCN method,NGAL,SF and sTfR by ELISA. TFR-F index and BIC were calculated according to the relevant index formula. [Result] There were significant correlation between NGAL and sTfR,TFR-F and BIC (the partial correlation

  17. 儿童血清中性粒细胞明胶酶相关脂质运载蛋白与维生素A代谢指标相关性研究%Relationship between serum neutrophil gelatinase-associated lipocalin and vitamin A metabolic index in preschool children

    Institute of Scientific and Technical Information of China (English)

    陈科; 章岚; 程昕然; 罗红裔; 高宁; 王劲; 傅桂英; 毛萌

    2012-01-01

    [Objective] To explore the correlation of neutrophil gelatinase-associated lipocalin (NGAL) and vitamin A metabolic index,including serum retinol,serum retinol binding protein (RBP) ,serum transthyretin (TTR) and the molar ratio of RBP to TTR[R-T index,RBP(mol/L)/TTR(mol/L)]. [Methods] About 473 preschool children with 2~7 years old were randomly selected from eight kindergartens,including 223 boys and 250 girls with (47. 8 ± 14. 5) months. Serum retinol was measured by HPLC method,NGAL and RBP by ELISA and TTR by immunoturbidimetric method. [Results] There were significant negative correlations between NGAL and retinol and R-T index(The partial correlation coefficients were - 0. 21 and - 0. 25 ;P aLL0. 05). The serum retinol and R-T index levels in children with Q1 RBP value group (cut by RBP 4 quartile level) was significantly higher than those of children with Q4 RBP value group (P0. 05). [Conclusion] There is close relation between serum NGAL and vitamin A status in preschool children and vitamin A may be able to inhibit the expression of NGAL which against the inhibition of NGAL on hematopoietic system.%[目的]初步分析中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)水平与维生素A代谢指标血清视黄醇、视黄醇结合蛋白(retinol-binding protein,RBP)、甲状腺素运载蛋白(transthyretin,TTR)的关系. [方法]随机抽取研究现场8所幼儿园473名2~7岁(不足7岁)学龄前儿童纳入.分别利用HPLC法测血清视黄醇;采用ELISA法测NGAL与RBP,采用免疫比浊法测TTR,并计算R-T指数[RBP (mol/L)/TTR(mol/L)]. [结果]血清NGAL与血清视黄醇和R-T指数存在明显负相关关系(偏相关系数r分别为-0.21和-0.25;P均<0.000 1).维生素A正常组儿童NGAL水平显著低于维生素A不正常组儿童(P<0.05).以指标中位数为界,低R-T指数组儿童血清NGAL水平明显高于高R-T组儿童(P<0.05),但是高与低RBP组儿童之间

  18. Plasma Neutrophil Gelatinase-Associated Lipocalinin in the General Population

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan S; Mogelvang, Rasmus;

    2014-01-01

    , when both markers were added to the Framingham risk score, NGAL conferred 3× to 4× the risk. CONCLUSIONS: Plasma NGAL is strongly associated with inflammation in the general population. NGAL independently associated with 10-year outcome, and when added to the Framingham risk score, NGAL both improves c...

  19. Urinary Neutrophil Gelatinase-Associated Lipocalin Levels in Neonates

    Directory of Open Access Journals (Sweden)

    Chi-Nien Chen

    2016-06-01

    Conclusion: This study presents preliminary data on uNGAL levels in neonates in Taiwan. A large-scale study investigating the correlations between uNGAL and with gestational age, birth body weight, sex, and PNA is recommended.

  20. Serum haptoglobin-matrix metalloproteinase 9 (Hp-MMP 9) complex as a biomarker of systemic inflammation in cattle.

    Science.gov (United States)

    Bannikov, G A; Hinds, C A; Rajala-Schultz, P J; Premanandan, C; Rings, D M; Lakritz, J

    2011-01-01

    A reliable and specific test that discriminates between acute neutrophil activation and chronic inflammatory disease may be useful in clinical decision making in a variety of conditions encountered in veterinary medical practice. An ELISA specific for neutrophil-derived haptoglobin-matrix metalloproteinase 9 (Hp-MMP 9) complexes was used to determine serum concentrations of Hp-MMP 9 and was compared to ELISA assays for Haptoglobin (Hp) and matrix metalloproteinase 9 (MMP 9) in 15 animals with acute sepsis, 10 animals with chronic inflammatory or metabolic disease and 10 healthy cows. Animal disease classifications were completed prior to the determination of serum concentrations of the 3 proteins. Duration of illness, disease process and lesions observed at necropsy were used to place animals into a specific classification. The serum MMP 9 concentrations in healthy cows differed significantly from those measured in sera of acutely septic and chronically ill animals. Serum haptoglobin concentrations in healthy cows were negligible when compared to animals with acute septic or chronic diseases. There was substantial overlap in MMP 9 and Hp concentrations between acute and chronic disease animals. In contrast, serum concentrations of Hp-MMP 9 complexes found almost exclusively in sera from acutely septic animals but not in chronically ill and normal cattle. The Hp-MMP 9 ELISA may be the serological test of choice in the determination of systemic inflammation associated with bacterial sepsis.

  1. Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Antonietta Rosella; Mackay, Andrew Reay, E-mail: andrewreay.mackay@univaq.it [Department of Applied Clinical and Biotechnological Sciences, University of L’Aquila, Via Vetoio, Coppito 2, L’Aquila 67100 (Italy)

    2014-01-27

    Since its original identification as a leukocyte gelatinase/type V collagenase and tumour type IV collagenase, gelatinase B/matrix metalloproteinase (MMP)-9 is now recognised as playing a central role in many aspects of tumour progression. In this review, we relate current concepts concerning the many ways in which gelatinase B/MMP-9 influences tumour biology. Following a brief outline of the gelatinase B/MMP-9 gene and protein, we analyse the role(s) of gelatinase B/MMP-9 in different phases of the tumorigenic process, and compare the importance of gelatinase B/MMP-9 source in the carcinogenic process. What becomes apparent is the importance of inflammatory cell-derived gelatinase B/MMP-9 in tumour promotion, early progression and triggering of the “angiogenic switch”, the integral relationship between inflammatory, stromal and tumour components with respect to gelatinase B/MMP-9 production and activation, and the fundamental role for gelatinase B/MMP-9 in the formation and maintenance of tumour stem cell and metastatic niches. It is also apparent that gelatinase B/MMP-9 plays important tumour suppressing functions, producing endogenous angiogenesis inhibitors, promoting inflammatory anti-tumour activity, and inducing apoptosis. The fundamental roles of gelatinase B/MMP-9 in cancer biology underpins the need for specific therapeutic inhibitors of gelatinase B/MMP-9 function, the use of which must take into account and substitute for tumour-suppressing gelatinase B/MMP-9 activity and also limit inhibition of physiological gelatinase B/MMP-9 function.

  2. Clinical significance of levels of serum osteopontin and neutrophil gelatinase -associated lipocalin in patients with polycystic ovary syndrome%血清骨桥蛋白及中性粒细胞明胶酶相关脂质运载蛋白水平在多囊卵巢综合征中的临床意义

    Institute of Scientific and Technical Information of China (English)

    莫轶晖; 张进; 杨丽丽

    2015-01-01

    目的:探讨多囊卵巢综合征(PCOS)患者血清骨桥蛋白(OPN)与中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的水平及其临床意义。方法:62例 PCOS 患者及同期健康体检的30例正常对照者分别采用酶联免疫法(ELISA)检测血清 OPN 和 NGAL 的水平,同时根据体重指数(BMI)将 PCOS 患者分为肥胖组32例(BMI≥25kg/m2)和非肥胖组30例(BMI <25kg/m2)。结果:与正常对照组相比较,所有 PCOS 患者血清中 OPN 和 NGAL 含量均显著偏高;肥胖 PCOS 患者血清中的 OPN 和 NGAL 水平也均明显高于非肥胖 P-COS 患者,差异具有统计学意义(P <0.05)。此外,Pearson 相关分析结果显示血清 OPN 及 NGAL 均与 BMI、胰岛素抵抗指数(HOMA -IR)呈正相关性,与胰岛素敏感指数(ISI)呈负相关性,差异具有统计学意义(P <0.05)。结论:多囊卵巢综合征患者血清中 OPN 和 NGAL 水平均处于升高状态,提示 PCOS 患者机体处于一种慢性炎性状态,未来可将减缓机体炎性状态作为治疗 PCOS 患者的策略之一。%Objectives:To investigate clinical significance of levels of serum osteopontin and neutrophil ge-latinase -associated lipocalin in patients with polycystic ovary syndrome.Methods:The levels of serum levels of OPN and NGAL of 62 PCOS patients and 30 healthy people as normal control were detected by using enzyme -linked immunoassay (ELISA).According to body mass index (BMI),patients with PCOS were divided into two groups:32 cases in obese group (BMI≥25kg/m)2 and 30 cases in non -obese group (BMI <25kg/m2 ).Results:Compared with normal control group,OPN and NGAL content in all PCOS patients were significantly higher.And OPN and NGAL levels of PCOS patients with obese were significantly higher than these of non -obese PCOS patients (P <0.05).In addition,Pearson correlation analysis results showed that there was a positive correlation between the

  3. Therapy with plasma purified alpha1-antitrypsin (Prolastin® induces time-dependent changes in plasma levels of MMP-9 and MPO.

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    Janine Koepke

    Full Text Available The common Z mutation (Glu342Lys of α1-antitrypsin (A1AT results in the polymerization and intracellular retention of A1AT protein. The concomitant deficiency of functional A1AT predisposes PiZZ subjects to early onset emphysema. Clinical studies have implied that, among the biomarkers associated with emphysema, matrix metalloproteinase 9 (MMP-9 is of particular importance. Increased plasma MMP-9 levels are proposed to predict the decline of lung function as well as greater COPD exacerbations in A1AT deficiency-associated emphysema. The aim of the present study was to investigate the effect of A1AT therapy (Prolastin on plasma MMP-9 and myeloperoxidase (MPO levels. In total 34 PiZZ emphysema patients were recruited: 12 patients without and 22 with weekly intravenous (60 mg/kg body weight A1AT therapy. The quantitative analysis of A1AT, MMP-9 and MPO was performed in serum and in supernatants of blood neutrophils isolated from patients before and after therapy. Patients with Prolastin therapy showed significantly lower serum MMP-9 and MPO levels than those without therapy. However, parallel analysis revealed that a rapid infusion of Prolastin is accompanied by a transient elevation of plasma MMP-9 and MPO levels. Experiments with freshly isolated blood neutrophils confirmed that therapy with Prolastin causes transient MMP-9 and MPO release. Prolastin induced the rapid release of MMP-9 and MPO when added directly to neutrophil cultures and this reaction was associated with the presence of IgA in A1AT preparation. Our data support the conclusion that changes in plasma levels of MMP-9 and MPO mirror the effect of Prolastin on blood neutrophils.

  4. 中性粒细胞明胶酶相关载脂蛋白在非小细胞肺癌组织的表达%Expression of neutrophil gelatinase-associated lipocalin in non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    李岩; 任淑华; 刘立新; 周海英; 李欣

    2016-01-01

    Objective To investigate the neutrophil gelatinase-associated lipocalin (NGAL) expression and clinical significance in non-small cell lung cancer (NSCLC) tissues.Methods The surgical treatment of non-small cell lung cancer patients resected tumor specimens of 130 cases of the experimental group,the distance of the cut edge of tumor more than 5cm much cancerous tissue as a control group,60 cases of adenocarcinoma,squamous cell carcinoma and 70 cases.By real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) method to detect NGAL mRNA expression in NSCLC tissues;the protein was detected by immunohistochemistry NSCLC tissues NGAL,NGAL expression and analysis and clinical characteristics of patients with protein relationship.Results (1) Adenocarcinoma NGAL mRNA real-time fluorescence quantitative results and ACt difference of β-actin (-2.9 ± 1.4),and squamous cell carcinoma (-2.4 ± 1.1) compared to no significant difference (P > 0.05);Adjacent tissues (-1.5 ± 1.4) compared with adenocarcinoma and squamous cell carcinomas (P < 0.05).(2) Non-small cell lung cancer,squamous cell carcinoma NGAL protein positive rate 55.71% (39/70),adenocarcinoma positive rate was 78.33% (47/60),adjacent tissues was 31.53% (41/130),three positive expression rate difference was statistically significant (x2 =5.942,P < 0.05).(3) Non-small cell lung cancer NAGL protein expression and patient' s age,sex,smoking and lymph node metastasis was no significant correlation (P > 0.05).Conclusion NGAL in the non-small cell lung cancer was highly expressed,and the classification of non-small cell lung cancer-related,may be an early diagnosis of non-small cell lung cancer a marker.%目的 探讨中性粒细胞明胶酶相关载脂蛋白(NGAL)在非小细胞肺癌(NSCLC)组织中的表达及意义.方法 以130例NSCLC患者切除肿块标本作为实验组,肿块边缘5 cm以上的远癌组织作为对照组,其中腺癌60例,鳞癌70例.通过实时荧光定量聚合酶

  5. Polymorphisms of the MMP-9 gene and abdominal aortic aneurysm

    Science.gov (United States)

    Smallwood, Linda; Allcock, Richard; van Bockxmeer, Frank; Warrington, Nicole; Palmer, Lyle J; Iacopetta, Barry; Golledge, Jonathan; Norman, Paul E

    2008-01-01

    Background Increased matrix metalloproteinase-9 (MMP-9) activity has been implicated in the formation of abdominal aortic aneurysms (AAAs). The aim of the present study was to explore the association between potentially functional variants of the MMP-9 gene and AAA. Method The −1562C>T and −1811A>T variants of the MMP-9 gene were genotyped in 678 men with AAAs (>30mm in diameter) and 659 controls (aortic diameter 19−22mm) recruited from a population-based trial of screening for AAAs. The levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed using multivariate logistic regression. Results There was no association between the MMP-9 −1562C>T (OR 0.70 95%CI 0.27, 1.82) or −1811A>T (OR 0.71, 95%CI 0.28, 1.85) genotypes, or the most common haplotype (OR 0.81 95%CI 0.62, 1.05), and AAA. The serum MMP-9 concentration (ng/mL) was higher in cases than controls and in minor allele carriers in cases and controls although the differences were not statistically significant. Conclusion The results suggest that a genetic tendency to have higher levels of circulating MMP-9 is not associated with AAAs. PMID:18763261

  6. Association of MMP-9 gene polymorphisms with nephrolithiasis patients.

    Science.gov (United States)

    Mehde, Atheer Awad; Mehdi, Wesen Adel; Yusof, Faridah; Raus, Raha Ahmed; Zainal Abidin, Zaima Azira; Ghazali, Hamid; Abd Rahman, Azlina

    2017-02-15

    Nephrolithiasis is one of the causes which lead to chronic kidney disease (CKD). Matrix metalloproteinases (MMPs) are endopeptidases degrading extracellular matrix which correlate with the pathogenesis of atherosclerosis. The current study was designed to analyze the association of (R279Q, C1562T) polymorphism of MMP-9 with nephrolithiasis patients. Genotyping of MMP-9/R279Q and of MMP-9/C1562T polymorphism were carried out by PCR-based restriction digestion method. Serum level of MMP-9, oxidative stress marker, MDA, and uric acid were measured in patients and control. Allele frequencies of the MMP-9/C1562T polymorphism for C and T allele were 71.25% and 28.75% in patients, 87.08% and 12.92% in control respectively. The homozygote TT was more frequent in the nephrolithiasis patients group, while T allele frequency was significantly higher in the nephrolithiasis patients group than in the control group. The patients with CT and TT genotype showed a significant increase in serum MMP-9, Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Malondialdehyde (MDA), and uric acid when compared to CC genotype in patients with nephrolithiasis. The R279Q polymorphism site with regard to the relationship with nephrolithiasis was not significant. The result indicates that patients with TT genotype had an increased risk of stones. Also, the results demonstrate that TT allele of the C1562T polymorphism in the MMP-9gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with TT genotype of MMP-9. © 2017 Wiley Periodicals, Inc.

  7. Serum Levels of Gelatinase Associated Lipocalin as Indicator of the Inflammatory Status in Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Nikolaos Kafkas

    2012-01-01

    Full Text Available Background. Atherosclerosis is a chronic inflammatory disease and the acute clinical manifestations represent acute on chronic inflammation. Neutrophil gelatinase-associated lipocalin (NGAL is found in the granules of human neutrophils, with many diverse functions. The aim of this study was to evaluate the hypothesis that levels NGAL in blood may reflect the inflammatory process in various stages of coronary artery disease. Methods. We studied 140 patients, with SA 40, UA 35, NSTEMI 40, and STEMI 25, and 20 healthy controls. Serum NGAL was measured upon admission and before coronary angiography. Results. Significant differences were observed in median serum-NGAL(ng/mL between patients with SA (79.23 (IQR, 37.50–100.32, when compared with UA (108.00 (68.34–177.59, NSTEMI (166.49 (109.24–247.20, and STEMI (178.63 (111.18–305.92 patients and controls (50.31 (44.30–69.78 with significant incremental value from SA to STEMI. We observed a positive and significant correlation between serum-NGAL and hs-CRP (spearman coefficient rho = 0.685, <0.0001 as well as with neutrophil counts (r = 0.511, <0.0001. Conclusions. In patients with coronary artery disease serum levels of NGAL increase and reflect the degree of inflammatory process. In patients with acute coronary syndromes, serum levels of NGAL have high negative predictive value and reflecting the inflammatory status could show the severity of coronary clinical syndrome.

  8. Clinical research on plasma and urine neutrophil gelatinase-associated lipocalin of lupus nephritis%狼疮性肾炎患者检测血、尿中性粒细胞明胶酶相关脂质运载蛋白的临床研究

    Institute of Scientific and Technical Information of China (English)

    谢伟基; 张夏兰; 张丽玲; 洪楷; 肖再雄; 陈东晓; 耿义群

    2010-01-01

    目的 测定狼疮性肾炎(LN)患者和健康成年人的血、尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)并分析其临床意义.方法 选取符合1997年美国风湿病学会修订的系统性红斑狼疮的诊断标准,同时合并有不同程度肾损害而确诊合并LN患者35例作为研究组,选取年龄、性别相匹配的健康成年人30例作为对照组,采用酶联免疫吸附技术(ELISA)分别测定血、尿NGAL的水平.另依据SLEDAI-2K的肾病活动指数将研究组患者分为肾病活动组(25例)与非肾病活动组(10例),并比较血、尿NGAL水平.结果 研究组患者尿NGAL水平为(78.94±81.97)μg/L,明显高于对照组的(28.50±18.08)μg/L,差异有统计学意义(P=0.002).肾病活动组尿NGAL水平为(92.90±94.88)μg/L,明显高于非肾病活动组的(48.20±24.77)μg/L,差异有统计学意义(P=0.049),两组血NGAL水平比较差异无统计学意义(P>0.05).结论 LN患者尿NGAL可作为肾病活动性的指标,其升高原因可能与肾小管病变有关.%Objective To study the clinical significance ofneutrophil gelatinase-associated lipocalin (NGAL), which in serial plasma and urine samples was measured in participants with lupus nephritis (LN)and healthy persons. Methods NGAL in serial plasma and urine samples was measured by enzyme-linked immunosorbent assay (EL.ISA) in 35 patients with LN by 1997 ACR systemic lupus erythematosus (SLE)standard with varied degree of kidney damage and 30 healthy persons with matching sex and age in physical examination center. Disease activity was measured by the SLE disease activity index (SLEDAI-2K),and 35LN patients were classified in active group and (25 cases) non-active group (10 cases) according to the SLEDAI-2K. Results Urinary NGAL were significantly increased in LN patients [(78.94 ± 81.97) μg/L]compared with healthy persons[(28.50 ± 18.08) μ g/L] (P = 0.002). And urinary NGAL were significantly increased in active group [(92.90 ± 94.88)

  9. Detection of MMP-2 and MMP-9 in the Lesions of Psoriasis%银屑病皮损中MMP-2 MMP-9的检测

    Institute of Scientific and Technical Information of China (English)

    陈晋广; 任小丽; 胡雅玉; 陈祥恩

    2005-01-01

    目的探讨MMP-2,MMP-9在细胞外基质(ECM)降解和银屑病发病机理中的作用及意义.方法采用免疫组化ABC法检测银屑病患者皮损中MMP-2,MMP-9.结果银屑病皮损中既可检测到MMP-2,又可检测到MMP-9,而在正常皮肤则为阴性.结论MMP-2,MMP-9参与了银屑病的发病过程.

  10. Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS.

    Science.gov (United States)

    Ranjbaran, Javad; Farimani, Marzieh; Tavilani, Heidar; Ghorbani, Marzieh; Karimi, Jamshid; Poormonsefi, Faranak; Khodadadi, Iraj

    2016-04-01

    It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.

  11. Study of the relationship of MMP-9 and serum fructosamine levels in diabetic retinopathy patients

    Directory of Open Access Journals (Sweden)

    Chong Wang

    2014-05-01

    Full Text Available AIM: To explore the relationship of MMP-9 and serum fructosamine levels and further illustrate the role of the development in diabetic retinopathy patients.METHODS: Serum MMP-9 levels were measured using enzyme-linkedimmunosorbent assays a in 30 health controls and 30 diabetic retinopathy patients, the relationship of MMP-9 and serum fructosamine levels were analyzed。RESULTS: Compared with healthy controls. The expression levels of MMP-9 indiabetic retinopathy patients were significantly increased \\〖(8.14±2.28pmol/L, vs(2.47±1.41pmol/L\\〗, MMP-9 were positive correlation with fructosamine(r=0.94, PCONCLUSION:The occurrence and progress of diabetic retinopathy might be closely related to the expression level of MMP-9, and the abnormal expression of MMP-9 in patients' serum might be associated with the secretion of fructosamine.

  12. Involvement of TSP1 and MMP9/NGAL in Angiogenesis during Orthodontic Periodontal Remodeling

    Directory of Open Access Journals (Sweden)

    Petra Surlin

    2014-01-01

    Full Text Available In the present study the aim was to measure the levels of Thrombospondin-1 (TSP1 and Lipocalin-2/matrix metalloproteinase 9 (MMP9/NGAL complex in gingival crevicular fluid (GCF at different time points of orthodontic treatment, to determine the relationship between these values and those of total-matrix metalloproteinase 9 (MMP9 and theirs implication in angiogenesis balance, in the situation of a good control of the bacterial plaque, emphasizing the role of TSP1 and MMP9/NGAL complex. GCF samples were collected from 16 young orthodontic patients requiring upper canine distalization (test tooth with first premolar extraction. The contralateral canine (control tooth was free from orthodontic force. For the orthodontic appliance, brackets Roth 0.018 inch with 0.012 inch NiTi archwire and a laceback were used. TSP1, MMP9/NGAL, and MMP9 increased from 1 hour before activation of orthodontic appliance to a maximum at 8 hours for MMP9 and 72 hours for MMP9/NGAL and TSP1. The results show a change in time of TSP1, MMP9/NGAL, and MMP9 levels in GCF of patients with this method of orthodontic treatment. The powerful correlation of MMP9/NGAL with TSP1 suggests their stronger involvement in angiogenesis processes in PDL during orthodontic periodontal remodeling, in the situation of a healthy periodontium and a good control of the bacterial plaque.

  13. Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Cuiyun Sun; Qian Wang; Hongxu Zhou; Shizhu Yu; Alain R.Simard; Chunsheng Kang; Yanyan Li

    2013-01-01

    The matrix-degrading metalloproteinases (MMPs),particularly MMP-9,play important roles in the pathogenesis and development of malignant gliomas.In the present study,the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo.TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA (pcDNA-ASMMP9),which significantly decreased MMP-9 expression,and cell proliferation was assessed.For in vivo studies,U251 cells,a human malignant glioma cell line,were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice.The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex (AS-MMP-9-treated group),subcutaneous injection of endostatin (endostatin-treated group),or both (combined therapy group).Mice treated with pcDNA (empty vector)-Lipofectamine served as the control group.Four or eight weeks later,the volume and weight of tumor,MMP-9 expression,microvessel density and proliferative activity were assayed.We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation.Volume and weight of tumor,MMP-9 expression,microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group.The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness,but also affects tumor cell proliferation.Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells,and thus can be used as an effective therapeutic strategy for malignant gliomas.

  14. 中性粒细胞明胶酶相关脂质运载蛋白鉴别革兰阳性菌与革兰阴性菌感染的实验研究%Value of neutrophil gelatinase-associated lipocalin in differential diagnosis of gram-positive and gram-negative bacterial infections:an animal experimental study

    Institute of Scientific and Technical Information of China (English)

    谢尹晶; 段晋燕; 张洪瑞; 刘一凡; 吴小利; 唐红卫; 杨继勇; 罗燕萍; 王成彬

    2015-01-01

    目的:通过建立全身感染性疾病小鼠模型,探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL )在鉴别诊断革兰阳性菌感染和革兰阴性菌感染方面的价值。方法选择216只IC R小鼠,每组8只,通过尾静脉分别注射金黄色葡萄球菌和大肠埃希菌,建立革兰阳性菌和革兰阴性菌所致的小鼠全身感染模型,分别在感染后1、3、6、12 h及1、2、3、5、7 d处死各组小鼠,检测其血清NGAL浓度。结果金黄色葡萄球菌感染组的小鼠NGAL浓度在感染后3 h明显升高,为(926.84±245.76)ng/ml ,大肠埃希菌感染组的小鼠NGAL浓度在感染后1 h明显升高,为(554.34±47.63)ng/ml;ROC曲线分析显示,金黄色葡萄球菌感染组和大肠埃希菌感染组 NGAL 的ROC曲线下面积(AUC)分别为0.908、0.979,两者差异无统计学意义。结论 NGAL在感染早期即明显升高,但其变化在金黄色葡萄球菌和大肠埃希菌引发的小鼠感染模型之间并无差异。%OBJECTIVE To explore the value of neutrophil gelatinase‐associated lipocalin(NGAL) in differential di‐agnosis of gram‐positive and gram‐negative bacteria infections by establishing systemic infectious mouse model . METHODS Totally 216 ICR mice were grouped ,with 8 mice in each group;the Staphylococcus aureus and Esche‐richia coli were respectively injected through tail vein so as to establish the gram‐positive bacteria‐and gram‐nega‐tive bacteria‐induced mice systemic infection model .The mice in each group were killed at 1 ,3 ,6 ,and 12 hours as well as at 1 ,2 ,3 ,5 ,and 7 days of being infected ,and the concentrations of serum NGAL were determined . RESULTS The concentration of NGAL of the mice infected with S .aureus was significantly elevated at 3 hours af‐ter being infected ,which was (926 .84 ± 245 .76)ng/ml;the concentration of NGAL of the mice infected with E .coli was remarkably elevated at 1 hour

  15. NDRG1 Controls Gastric Cancer Migration and Invasion through Regulating MMP-9.

    Science.gov (United States)

    Chang, Xiaojing; Xu, Xiaoyang; Xue, Xiaoying; Ma, Jinguo; Li, Zhenhua; Deng, Peng; Chen, Jing; Zhang, Shuanglong; Zhi, Yu; Dai, Dongqiu

    2016-10-01

    The purpose of this study is to detect the clinical significance of NDRG1 and its relationship with MMP-9 in gastric cancer metastatic progression. 101 cases of gastric cancer specimens were utilized to identify the protein expression of NDRG1 and MMP-9 by immunohistochemistry, their clinical significance was also analyzed. The suppression by siRNA-NDRG1 was employed to detect the role of NDRG1 in gastric cancer progression and its relationship with MMP-9. NDRG1 expression was correlated inversely with the degree of tumor cell differentiation (p 0.05). Furthermore, cell proliferation and invasion effect were remarkably enhanced when NDRG1 was silencing, but MMP-9 expression was increased. NDRG1 silencing enhances gastric cancer cells progression through upregulating MMP-9. It suggests that NDRG1 may inhibit the metastasis of gastric cancer via regulating MMP-9.

  16. Combined spectroscopy and molecular modeling studies on the binding of galbanic acid and MMP9.

    Science.gov (United States)

    Kiani, Amir; Almasi, Khadijeh; Shokoohinia, Yalda; Sadrjavadi, Komail; Nowroozi, Amin; Shahlaei, Mohsen

    2015-11-01

    The molecular mechanism of galbanic acid (GBA) binding to matrix metalloproteinase 9 (MMP9) was investigated by fluorescence quenching, absorption spectroscopy, FT-IR, molecular docking and molecular dynamics (MD) simulation procedures. The fluorescence emission of MMP9 was quenched by GBA. The titration of MMP9 by various amount of GBA was also followed by UV-Vis absorption spectroscopy. The results revealed that GBA, as a biologically active sesquiterpene coumarin derivative, has an ability to bind strongly to MMP9. Molecular docking results indicated that the main active binding site for GBA has been located in a hydrophobic cavity in the vicinity of Zn atom. Moreover, MD simulation results suggested that GBA as a coumarin derivative can interact with MMP9, without affecting the secondary structure of MMP9. MD simulations, molecular docking as computational methods from one hand and experimental data from other hand reciprocally supported each other.

  17. Signatures of positive selection at hemopexin (PEX) domain of matrix metalloproteinase-9 (MMP-9) gene

    Indian Academy of Sciences (India)

    Yang Liu; Yang Zhao; Chunlei Lu; Maobin Fu; Tonghai Dou; Xiaoming Tan

    2015-12-01

    Matrix metalloproteinases-9 (MMP-9) is an important cancer-associated, zinc-dependent endopeptidase. To investigate the natural selection hypothesis of MMP-9, the orthologous sequences from 12 vertebrates were compared and a molecular evolution analysis was performed. Results suggest that amino acid residues present in the middle region of the protein are more selectively constrained, whereas amino acid residues in the C-terminal region of the MM~P-9 protein including exon 13 showed lowest conservation level in non-primate species, suggesting that it is an exon with fast evolving rate compared to the others analyzed. InterProScan analysis shows that exon 13 was located in hemopexin (PEX) domain of MM~P-9. Positive selection was detected in PEX domain of MMP-9 protein between human and other species, which indicates that selective pressure may play a role in shaping the function of MM~P-9 in the course of evolution.

  18. Correlation of neutrophil gelatinase - associated lipocalin with dialysis adequacy,microinflammation and iron metabolism in maintenance hemodialysis patients%维持性血液透析患者血清中性粒细胞明胶酶相关载脂蛋白水平与透析充分性、铁代谢及微炎性反应状态的相关性

    Institute of Scientific and Technical Information of China (English)

    李占园; 黄文; 郑育; 叶菡洋; 金领微; 叶白如; 周志宏

    2012-01-01

    目的 研究维持性血液透析(MHD)患者血清中性粒细胞明胶酶相关载脂蛋白(NGAL)水平与透析充分性、微炎性反应状态及铁代谢的关系;探讨NGAL对判断透析充分性的价值.方法 从2010年10月开始,纳入我院MHD患者150例为对象,同时以50例健康人为对照.收集MHD患者的人口学资料、临床表现及检测参试者血清NGAL、C反应蛋白( CRP)、转铁蛋白饱和度(TSAT)、铁蛋白等水平.根据单室尿素清除指数(spKt/V)值将MHD 患者分为透析充分组和不充分组,比较组间血清NGAL差异.用Pearson相关法、多元线性回归模型和受试者工作特征(ROC)曲线分析NAGL与Kt/V、炎性因子和铁代谢指标等相关性.患者随访3个月,对比两组随访前后NAGL、Kt/V及炎性因子变化,进一步评估血清NGAL与透析充分性、炎性指标的关系.结果 MHD患者血清NGAL为(445.45±50.34) μg/L,显著高于健康对照的(50.02±6.45) μg/L(P<0.01).150例MHD患者中,95例为充分组,55例为不充分组.充分组与不充分组NGAL分别为(589.14±56.34) μg/L和(360.13±46.23)μg/L,差异有统计学意义(P<0.05).MHD患者血清NGAL与spKt/V、CRP、TSAT呈正相关(r=0.652、0.825、0.785,均P<0.05).多元线性回归模型结果显示,NGAL与CRP、spKt/V、TSAT有相关关系.ROC曲线下面积(AUC)表明,NGAL水平能较好地反映透析充分性.随诊后结果显示,所有充分组患者均维持透析充分状态;经干预后,不充分组中38例达透析充分,另17例仍未达到透析充分.在这38例中,未达充分和达充分时的NGAL分别为(368.14±56.21) μg/L和( 360.56±46.23) μg/L,差异无统计学意义.CRP水平达充分后有所下降,但差异无统计学意义.结论 MHD透析充分患者血清NGAL显著高于不充分患者.MHD患者血清NGAL与spKt/V、CRP及TSAT均呈正相关.血清NGAL能较好地反映透析充分性.%Objective To examine the correlation of serum neutrophil gelatinase-associated

  19. Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon.

    Science.gov (United States)

    Chen, Menglu; Gao, Lei; Chen, Pan; Feng, Dandan; Jiang, Yalin; Chang, Yongchao; Jin, Jianjun; Chu, Fong-Fong; Gao, Qiang

    2016-01-01

    Background. 5-HT enhances dextran sulfate sodium- (DSS-) induced colitis and is involved in inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) play roles in the process of intestinal inflammation. Aims. To examine whether 5-HT induces MMPs expression in mouse colon to enhance DSS-induced colitis. Materials and Methods. C57BL/6J (B6) mice were treated with either low-dose (1.0 mg/kg) or high-dose (2.0 mg/kg) 5-HT by enema, low-dose (1.0%) or high-dose (2.5%) DSS, or combined low-dose (1.0%) DSS and (1.0 mg/kg) 5-HT. Mouse colitis was analyzed. MMPs and tissue inhibitors of MMPs (TIMPs) mRNA were measured by real-time quantitative RT-PCR in mouse colon and in human Caco-2 cells and neutrophils. MMP-3 and MMP-9 protein levels were quantified from immunohistochemistry (IHC) images of mouse colons. Results. 5-HT exacerbated DSS-induced colitis, low-dose 5-HT induces both MMP-3 and MMP-9, and high-dose 5-HT only increased MMP-3 mRNA expression in mouse colon. Mouse colon MMP-3 and MMP-9 protein levels were also elevated by 5-HT treatment. The MMP-2, TIMP-1, and TIMP-2 mRNA levels were increased in the inflamed colon. 5-HT induced MMP-3 and MMP-9 mRNA expression in Caco-2 and human neutrophils, respectively, in vitro. Conclusion. 5-HT induced MMP-3 and MMP-9 expression in mouse colon; these elevated MMPs may contribute to DSS-induced colitis.

  20. Waist circumference and neutrophil gelatinase-associated lipocalin in late-life depression

    NARCIS (Netherlands)

    Marijnissen, Radboud M.; Naude, Petrus J. W.; Comijs, Hannie C.; Schoevers, Robert A.; Oude Voshaar, Richard

    Both visceral obesity and depression are associated with impaired health and excess mortality, possibly through overlapping pathophysiological mechanisms like adipose tissue derived inflammatory markers. These results, however, are primarily based on population-based surveys, often restricted to a

  1. Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand.

    Science.gov (United States)

    Srisawat, Nattachai; Praditpornsilpa, Kearkiat; Patarakul, Kanitha; Techapornrung, Malee; Daraswang, Tinnapop; Sukmark, Theerapon; Khositrangsikun, Kamol; Fakthongyoo, Apinya; Oranrigsupak, Petchdee; Praderm, Laksamon; Suwattanasilpa, Ummarit; Peerapornratana, Sadudee; Loahaveeravat, Passisd; Suwachittanont, Nattachai; Wirotwan, Thaksa-on; Phonork, Chayanat; Kumpunya, Sarinya; Tiranathanagul, Khajohn; Chirathaworn, Chintana; Eiam-ong, Somchai; Tungsanga, Kriang; Sitprija, Visith; Kellum, John A; Townamchai, Natavudh

    2015-01-01

    AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting.

  2. Neutrophil Gelatinase-Associated Lipocalin : Ready for Routine Clinical Use? An International Perspective

    NARCIS (Netherlands)

    Ronco, Claudio; Legrand, Matthieu; Goldstein, Stuart L.; Hur, Mina; Nam Tran, [No Value; Howell, Eric C.; Cantaluppi, Vincenzo; Cruz, Dinna N.; Damman, Kevin; Bagshaw, Sean M.; Di Somma, Salvatore; Lewington, Andrew

    2014-01-01

    Acute kidney injury (AKI) remains a challenge in terms of diagnosis and classification, its morbidity and mortality remaining high in the face of improving clinical protocols. Current clinical criteria use serum creatinine (sCr) and urine output to classify patients. Ongoing research has identified

  3. The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease

    NARCIS (Netherlands)

    Gouweleeuw, Leonie; Naudé, Petrus; Rots, Marianne; de Jongste, Michel; Eisel, Ulrich; Schoemaker, Regina

    2015-01-01

    Depression is more common in patients with cardiovascular disease than in the general population. Conversely, depression is a risk factor for developing cardiovascular disease. Comorbidity of these two pathologies worsens prognosis. Several mechanisms have been indicated in the link between cardiova

  4. Urinary neutrophil gelatinase-associated lipocalin time course during cardiac surgery

    Directory of Open Access Journals (Sweden)

    Elena Bignami

    2015-01-01

    Full Text Available Background: NGAL is one of the most promising AKI biomarkers in cardiac surgery. However, the best timing to dose it and the reference values are still matter of discussion. Aim of the Study: We performed a uNGAL perioperative time course, to better understand its perioperative kinetics and its role in AKI diagnosis. Setting of the Study: San Raffaele University Hospital, cardiac surgery department. Material and Methods: We enrolled in this prospective observational study 19 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB. Based on preoperative characteristics, they were divided in low-risk and high-risk patients. uNGAL measurements were collected at pre-defined times before, during, and up to 24 hours after surgery. Statistical Analysis: Data were analysed by use of SAS 1999-2001 program or IBM SPSS Statistics. Results: In low-risk patients, uNGAL had the highest value immediately after general anesthesia induction (basal dosage: uNGAL: 12.20ng×ml -1 , IQR 14.00. It later decreased significantly (3.40 ng×ml -1 , IQR 4.80; P = 0.006 during CPB, and finally return to its original value 24 hours after surgery. In high-risk patients, uNGAL increased immediately after surgery; it had the highest value on ICU arrival (38,20 ng×ml -1 ; IQR 133,10 and remained high for several hours. A difference in uNGAL levels between the two groups was already observed at the end of surgery, but it became statistically significant on ICU arrival (P = 0.002. Conclusion: This study helps to better understand the different kinetics of this new biomarker in low-risk and high-risk cardiac patients.

  5. Neutrophil gelatinase-associated lipocalin and cystatin C in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Hurry, Preete Kapisha; Poulsen, Jørgen Hjelm; Bendtsen, Flemming

    2017-01-01

    and kinetics are sparsely studied in cirrhosis. In patients with cirrhosis and portal hypertension, we studied plasma levels and renal, hepatic, and peripheral extraction of NGAL and cystatin C and relations to patients characteristics, liver dysfunction, and hemodynamics. METHODS: Forty-five cirrhotic...... have the potential of being both valuable in diagnosing renal failure and reflecting the degree of portal hypertension and systemic haemodynamic changes....

  6. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery

    DEFF Research Database (Denmark)

    Wagener, G.; Gubitosa, G.; Wang, S.

    2008-01-01

    adult cardiac surgery. STUDY DESIGN: Diagnostic test accuracy. SETTING & PARTICIPANTS: Adult cardiac surgical patients (n = 426) in a single center from 2004 to 2006. INDEX TEST: Urinary NGAL immediately and 3, 18, and 24 hours after cardiac surgery, using an enzyme-linked immunosorbent assay. REFERENCE...... TEST OR OUTCOME: Serum creatinine-based definition for AKI (increase in serum creatinine from preoperative values by >50% or >0.3 mg/dL within 48 hours). RESULTS: Mean urinary NGAL level was 165 +/- 663 (SD) ng/mL preoperatively, peaked immediately after cardiac surgery at 1,490 +/- 102 ng...... to predict AKI defined by change in serum creatinine after cardiac surgery Udgivelsesdato: 2008/9...

  7. Waist circumference and neutrophil gelatinase-associated lipocalin in late-life depression

    NARCIS (Netherlands)

    Marijnissen, Radboud M.; Naude, Petrus J. W.; Comijs, Hannie C.; Schoevers, Robert A.; Oude Voshaar, Richard

    2014-01-01

    Both visceral obesity and depression are associated with impaired health and excess mortality, possibly through overlapping pathophysiological mechanisms like adipose tissue derived inflammatory markers. These results, however, are primarily based on population-based surveys, often restricted to a y

  8. Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9 and Their Inhibitors (TIMP-1, TIMP-2 in Inflammatory Bowel Diseases

    Directory of Open Access Journals (Sweden)

    Katarzyna Jakubowska

    2016-01-01

    Full Text Available Crohn’s disease (CD and ulcerative colitis (UC belong to a group of inflammatory bowel diseases (IBD. The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn’s disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases’ expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression.

  9. MMP-2和MMP-9在肺癌组织中的表达%Expression of MMP-2 and MMP-9 in Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    孙书明; 周妍; 罗金芳; 桂律; 胡志雄; 金盈; 金复生

    2003-01-01

    目的:研究肺癌和正常肺组织中基质金属蛋白酶2 (MMP-2)和MMP-9的表达.方法:采用免疫组织化学EnVision方法, 对71例肺癌标本和31例正常肺组织检测MMP-2和MMP-9的表达.结果:71例肺癌标本中,小细胞肺癌(SCLC)4例,MMP-2表达阳性3例(75.0%),MMP-9表达阳性2例(50.0%);非小细胞肺癌(NSCLC)有67例,年龄40岁以上64例,MMP-2表达阳性39例,阳性率60.9%(39/64);MMP-9表达阳性46例,阳性率71.9%(46/64).正常肺标本31例,年龄40岁以下MMP-2和MMP-9表达均为阴性,年龄在40岁以上26例,MMP-2阳性表达9例,阳性率34.6%(9/26),MMP-9阳性表达10例,阳性率38.5%(10/26);40岁以上NSCLC标本的MMP-2和MMP-9阳性表达与正常肺标本比较,差异均有显著意义.结论:在NSCLC中高表达的MMP-2和MMP-9均是好的肿瘤标记物,但是,MMP-9阳性率比MMP-2更高,因此MMP-9的检测具有更大的临床意义.

  10. Concomitant lack of MMP9 and uPA disturbs physiological tissue remodeling

    DEFF Research Database (Denmark)

    Lund, Ida K; Nielsen, Boye S; Almholt, Kasper

    2011-01-01

    Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9, gelatinase B) have separately been recognized to play important roles in various tissue remodeling processes. In this study, we demonstrate that deficiency for MMP9 in combination with ablation of either uPA- or tissue...

  11. Expression of MMP-9 and TIMP-1 in Lesions of Systemic Sclerosis and Its Implications

    Institute of Scientific and Technical Information of China (English)

    Chi MENG; Xu'e CHEN; Jiawen LI; Yan WU; Houjun LIU

    2008-01-01

    In order to investigate the role of MMP-9 and TIMP-1 in the pathogenesis of systemic sclerosis, the expression of MMP-9 and TIMP-1 was immunohistochemically detected in skin lesions of the patients with diffuse cutaneous systemic sclerosis, skin lesions of the patients with limited cutaneous systemic sclerosis, and skin tissues of normal subjects. The results showed that the expression of MMP-9 in lesions of diffuse cutaneous systemic sclerosis was significantly lower than that of normal skins (P<0.05). However, no significant difference in the level of MMP-9 in the limited cutaneous systemic sclerosis and normal skin was found. Meanwhile, the expression of TIMP-1 in lesions of diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis were significantly higher than that of normal skins (both P<0.05). It was suggested that the expression of MMP-9 and TIMP-1 might play an important role in the development of systemic sclerosis.

  12. Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia cells.

    Science.gov (United States)

    Liu, Wen-Hsin; Chen, Ying-Jung; Chien, Jen-Hung; Chang, Long-Sen

    2014-05-01

    This study explores the suppression mechanism of amsacrine (4-(9-Acridinylamino)-N-(methanesulfonyl)-m-anisidine hydrochloride) on matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in human leukemia cells. Amsacrine attenuated cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels in U937, Jurkat, HL-60, K562, KU812, and MEG-01 cells. Moreover, amsacrine reduced both MMP-2/MMP-9 promoter luciferase activity and MMP-2/MMP-9 mRNA stability in leukemia cells. Studies on amsacrine-treated U937 cells revealed that amsacrine-elicited ROS generation induced JNK and p38 MAPK activation but reduced the phospho-ERK level. Amsacrine-induced ERK inactivation and p38 MAPK/JNK activation were demonstrated to suppress MMP-2/MMP-9 promoter luciferase activity and promote MMP-2/MMP-9 mRNA decay, respectively. p38 MAPK/JNK activation led to up-regulation of protein phosphatase 2A catalytic subunit α (PP2Acα) in amsacrine-treated U937 cells. Okadaic acid (PP2A inhibitor) treatment increased MMP-2/MMP-9 mRNA stability in amsacrine-treated cells, whereas PP2Acα over-expression increased MMP-2/MMP-9 mRNA decay. Amsacrine-induced MMP-2/MMP-9 down-regulation was also related to PP2Acα up-regulation on Jurkat, HL-60, K562, KU812, and MEG-01 cells. Collectively, our data indicate that amsacrine induces MMP-2/MMP-9 down-regulation via simultaneous suppression of genetic transcription and mRNA stability in human leukemia cells.

  13. Abnormal expression of MMP-9 and imbalance of MMP-9/TIMP-1 is associated with prolonged uterine bleeding after a medical abortion with mifepristone and misoprostol.

    Science.gov (United States)

    Li, Li; Zhou, Zanhua; Huang, Lili

    2009-01-01

    To investigate the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitory of metalloproteinase-1 (TIMP-1) in women who had undergone a medical abortion and explore their possible role in the mechanism of prolonged uterine bleeding after a mifepristone-misoprostol abortion. Cross-sectional study. Tertiary referral university hospital. Forty women were recruited following a medical abortion with mifepristone and misoprostol, 20 with duration of bleeding >14 days and 20 with duration of bleeding 14 days after a medical abortion (bleeding group), whereas each sample of women with duration of bleeding after a medical abortion (control group) showed normal endometrial changes. Immunohistochemistry and semi-quantitative scoring showed a significantly decreased expression level of MMP-9 in the bleeding group, compared with the control group. There was no significant difference of TIMP-1 expression between the bleeding group and the control group. The MMP-9/TIMP-1 ratio value was significantly lower in the bleeding group than in the control group. This study documents that prolonged bleeding after a medical abortion with mifepristone and misoprostol is associated with retained products of conception with inflammatory cell infiltration, abnormal expression of MMP-9 and imbalance of MMP-9/TIMP-1.

  14. Expression of MMP-2 and MMP-9 in the rat trigeminal ganglion during the development of temporomandibular joint inflammation.

    Science.gov (United States)

    Nascimento, G C; Rizzi, E; Gerlach, R F; Leite-Panissi, C R A

    2013-11-18

    Orofacial pain is a prevalent symptom in modern society. Some musculoskeletal orofacial pain is caused by temporomandibular disorders (TMDs). This condition has a multi-factorial etiology, including emotional factors and alteration of the masticator muscle and temporomandibular joints (TMJs). TMJ inflammation is considered to be a cause of pain in patients with TMD. Extracellular proteolytic enzymes, specifically the matrix metalloproteinases (MMPs), have been shown to modulate inflammation and pain. The purpose of this investigation was to determine whether the expression and level of gelatinolytic activity of MMP-2 and MMP-9 in the trigeminal ganglion are altered during different stages of temporomandibular inflammation, as determined by gelatin zymography. This study also evaluated whether mechanical allodynia and orofacial hyperalgesia, induced by the injection of complete Freund's adjuvant into the TMJ capsule, were altered by an MMP inhibitor (doxycycline, DOX). TMJ inflammation was measured by plasma extravasation in the periarticular tissue (Evans blue test) and infiltration of polymorphonuclear neutrophils into the synovial fluid (myeloperoxidase enzyme quantification). MMP expression in the trigeminal ganglion was shown to vary during the phases of the inflammatory process. MMP-9 regulated the early phase and MMP-2 participated in the late phase of this process. Furthermore, increases in plasma extravasation in periarticular tissue and myeloperoxidase activity in the joint tissue, which occurred throughout the inflammation process, were diminished by treatment with DOX, a nonspecific MMP inhibitor. Additionally, the increases of mechanical allodynia and orofacial hyperalgesia were attenuated by the same treatment.

  15. Expression of MMP-2 and MMP-9 in the rat trigeminal ganglion during the development of temporomandibular joint inflammation

    Directory of Open Access Journals (Sweden)

    G.C. Nascimento

    2013-11-01

    Full Text Available Orofacial pain is a prevalent symptom in modern society. Some musculoskeletal orofacial pain is caused by temporomandibular disorders (TMDs. This condition has a multi-factorial etiology, including emotional factors and alteration of the masticator muscle and temporomandibular joints (TMJs. TMJ inflammation is considered to be a cause of pain in patients with TMD. Extracellular proteolytic enzymes, specifically the matrix metalloproteinases (MMPs, have been shown to modulate inflammation and pain. The purpose of this investigation was to determine whether the expression and level of gelatinolytic activity of MMP-2 and MMP-9 in the trigeminal ganglion are altered during different stages of temporomandibular inflammation, as determined by gelatin zymography. This study also evaluated whether mechanical allodynia and orofacial hyperalgesia, induced by the injection of complete Freund's adjuvant into the TMJ capsule, were altered by an MMP inhibitor (doxycycline, DOX. TMJ inflammation was measured by plasma extravasation in the periarticular tissue (Evans blue test and infiltration of polymorphonuclear neutrophils into the synovial fluid (myeloperoxidase enzyme quantification. MMP expression in the trigeminal ganglion was shown to vary during the phases of the inflammatory process. MMP-9 regulated the early phase and MMP-2 participated in the late phase of this process. Furthermore, increases in plasma extravasation in periarticular tissue and myeloperoxidase activity in the joint tissue, which occurred throughout the inflammation process, were diminished by treatment with DOX, a nonspecific MMP inhibitor. Additionally, the increases of mechanical allodynia and orofacial hyperalgesia were attenuated by the same treatment.

  16. MMP-9 directed shRNAs as relevant inhibitors of matrix metalloproteinase 9 activity and signaling

    Directory of Open Access Journals (Sweden)

    Ewa Nowak

    2013-08-01

    Full Text Available Introduction: The main function of matrix metalloproteinases is the degradation of extracellular matrix components, which is related to changes in the proliferation of cells, their differentiation, motility, and death. MMPs play an important role in physiological processes such as embryogenesis, angiogenesis and tissue remodeling. The increase of MMPs activity is also observed in pathological conditions including tumorigenesis where MMP-2 (gelatinase A and MMP-9 (gelatinase B show the ability to degrade the basement membrane of vessels and they are involved in metastasis. The aim of our study was to verify the changes of MMP-9 enzymatic activity and the mobility of cells after inhibition of MMP-9 gene expression.Material and Methods: The oligonucleotide shRNA insert had been designed to silence MMP-9 gene expression and was cloned into the pSUPER.neo expression vector. The construct was introduced into the HeLa (CCL-2 cervical cancer cells by lipotransfection. Simultaneously in control cells MMP-9 were inhibited by doxycycline. Changes in activity of MMP-9 were analyzed by gelatin zymography and wound-healing assay.Results/Conclusions: Gelatin zymography allowed us to confirm that activity of MMP-9 in cells transfected by shRNA-MMP-9 and treated by doxycycline were similar and significantly lower in comparison with control cells. Phenotypic tests of migration in vitro confirm statistically significant (P<0.05 changes in cell migration – control cells healed 3 to 5 times faster in comparison with transfected or doxycycline treated cells. Our studies show the significant role of MMP-9 in mobility and invasiveness of tumor cells, thus indicating a potential target point of interest for gene therapy.

  17. MMP-2和MMP-9在食管癌中表达的研究%Expressions of MMP-2 and MMP-9 in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    武志; 潘晓玲; 仲洁

    2013-01-01

    目的 分析基质金属蛋白酶(MMP)-2和MMP-9在食管癌患者血清中的表达与食管癌临床病理因素之间的关系.方法 应用酶联免疫吸附法检测60例食管癌患者血清中MMP-2、MMP-9的含量与患者年龄、性别、组织学类型、临床分期及区域淋巴结转移等临床病理因素之间的关系.结果 对照组血清中MMP-2和MMP-9的浓度均值分别为61.31、87.67 ng/ml,而食管癌患者血清中MMP-2和MMP-9的浓度均值分别121.66、169.73 ng/ml,均高于正常者血清中含量,差异有统计学意义(t=3.015,P=0.007;t=2.037,P=0.04).MMP-2的含量与有无淋巴结转移(t=2.150,P=0.04)及临床分期(t=2.186,P=0.03)有关,MMP-9的含量与有无淋巴结转移(t=2.390,P=0.02)及临床分期(t=2.149,P=0.03)有关.MMP-2和MMP-9的含量均与食管癌患者的年龄、性别、组织学类型无关(均P>0.05).结论 MMP-2和MMP-9可能与食管癌的侵袭转移有关.%Objective To analyze the expression levels of matrix metallo proteinase-2 (MMP-2) and matrix metallo proteinase-9 (MMP-9) in serum of patients with esophageal cancer,and to analyze the interrelations among MMP-2,MMP-9 and clinicopathologic characteristics of esophageal cancer.Methods The levels of serum MMP-2,MMP-9 from 60 patients with esophageal cancer were detected by enzyme linked immunosorbent assay.The interrelations among MMP-2,MMP-9 and clinicopathologic characteristics of esophageal cancer including age,gender,histological type,whether or not lymph nodes metastasis and TNM staging were analyzed.Results The levels of MMP-2 and MMP-9 in control group were 61.31 ng/ml and 87.67 ng/ml,the levels of MMP-2 and MMP-9 in patients with esophageal cancer were 121.66 ng/ml and 169.73 ng/ml.The levels of MMP-2 and MMP-9 were significantly higher in patients with esophageal cancer than that of general population (t =3.015,P =0.007; t =2.037,P =0.04).The level of MMP-2 was significantly associated with whether or not lymph node metastasis (t =2

  18. 尿液中MMP-2、MMP-9MMP-9/NGAL复合物的表达在乳腺癌筛查中的意义%The Clinical Significance of Determining Expressions of Urinary MMP-2,MMP-9 and MMP-9/NGAL Complex for Screening Patients with Breast Cancer in High-risk Female Population

    Institute of Scientific and Technical Information of China (English)

    申哲洙; 顾晋; 赵威; 张志谦

    2008-01-01

    目的 检测女性尿液中MMP-2、MMP-9MMP-9/NGAL复合物的表达,探讨其在乳腺癌高危发病妇女普查筛选中的意义.方法 采用明胶酶底物电泳法和Western blot方法,检测正常女性(n=60)、乳腺良性疾病患者(n=41)、乳腺癌患者(n=127)尿液中MMP-2、MMP-9MMP-9/NGAL复合物的表达情况.结果 MMP-2、MMP-9MMP-9/NGAL复合物的表达在正常女性尿液中分别为23.33%、15%和13.33%;在乳腺良性疾病患者尿液中分别为43.93%、39.02%和36.59%;在乳腺癌患者尿液中分别为64.56%、76.37%和70.08%.乳腺癌患者尿液中MMP-2、MMP-9MMP-9/NGAL复合物的表达与正常女性间差异有统计学意义(P<0.001);与乳腺良性疾病患者比较差异也有统计学意义(P<0.01).乳腺癌患者尿液中MMP-2+MMP-9+MMP-9/NGAL复合物同时表达,与乳腺良性疾病患者比较差异亦有统计学意义(P<0.01).结论 1)乳腺癌、乳腺良性疾病和正常女性尿液中MMP-2、MMP-9MMP-9/NGAL复合物均有表达.但正常女性很少表达MMP-2和MMP-9,极少表达MMP-9/NGAL复合物.2)乳腺癌患者尿液中MMP-2+MMP-9+MMP-9/NGAL复合物的同时表达,对乳腺癌的诊断具有重要意义.对乳腺癌高危发病妇女的普查筛选也具有指导意义.

  19. Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Sullu, Yurdanur; Demirag, Guzin G; Yildirim, Arzu; Karagoz, Filiz; Kandemir, Bedri

    2011-12-15

    Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p=0.001), triple-negative (ER, PR, HER2 negative) (p=0.006), and ER-negative tumors (p=0.004) and tumors with distant metastases (p=0.028). MMP-9 expression was increased in cases with HER2 over-expression/amplification, but no statistically significant difference was found (p=0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p=0.492 and p=0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p=0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p=0.042 and p=0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.

  20. A nonintrinsic regional basis for increased infrarenal aortic MMP-9 expression and activity.

    Science.gov (United States)

    Ailawadi, Gorav; Knipp, Brian S; Lu, Guanyi; Roelofs, Karen J; Ford, John W; Hannawa, Kevin K; Bishop, Keith; Thanaporn, Porama; Henke, Peter K; Stanley, James C; Upchurch, Gilbert R

    2003-05-01

    This investigation was undertaken to determine whether intrinsic or regional factors at different anatomic sites of the aorta affect expression and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Aortas from Sprague-Dawley rats (n = 22) were divided into arch, descending thoracic, and infrarenal abdominal segments. Specimens were stimulated with interleukin-1beta (IL-1beta) (2 ng/mL) for 72 hours. In separate experiments, syngeneic aortic segments were transplanted from the thoracic or abdominal aortas of donor rats into the infrarenal aortic position of recipient rats (n = 12 each). At 4 weeks, aortas from rats who had received transplants were harvested, sectioned into arch, thoracic, and transplanted thoracic or transplanted abdominal segments, and stimulated with IL-1beta. Reverse transcriptase polymerase chain reaction, zymography, and reverse zymography were performed to assess MMP-9, MMP-2, and TIMP-1 in all aortic segments. Differences were assessed with analysis of variance (ANOVA) and post-hoc Tukey test. In control rats, abdominal segments had significantly higher MMP-9 expression compared with arch and thoracic segments (P <.002). Total MMP-9 activity was also higher in abdominal segments (P <.02). In rats who received transplants, transplanted thoracic (P <.004) and transplanted abdominal (P <.05) segments demonstrated upregulation of MMP-9 expression, compared with control arch and thoracic segments. Zymography documented increased total MMP-9 activity in transplanted thoracic (P <.03) and transplanted abdominal (P <.04) segments versus arch and thoracic segments. No significant difference in MMP-9 expression was found between control abdominal, transplanted thoracic, or transplanted abdominal segments. No significant differences in MMP-2 or TIMP-1 expression or activity were demonstrated in either control or transplanted segments. These data demonstrate that variations in aortic MMP-9 expression and

  1. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae, E-mail: chidkim@pusan.ac.kr

    2012-04-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  2. Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Clausen, Rikke E; Nguyen, Quoc Hai Trieu;

    2012-01-01

    Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part...... are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases....

  3. Serum level of MMP-2, MMP-9 and Ox-LDL in Alzheimer's disease with hyperlipoidemia

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To investigate serum levels of MMP-2,MMP-9, oxidized low density lipoprotein (ox-LDL) in Alzheimer's disease (AD) patients and study the possible pathway and mechanism of AD with abnormal lipid metabolism. Methods: Subjects in this study were divided into 4 groups: normal lipid group without AD (N), hyperlipoidemia group without AD (H), normal group with AD (A), hyperlipoidemia group with AD (AH). There were 15 individuals in each group. MMP-2, MMP-9, ox-LDL was measured by enzyme linked immunosorbent assay (ELISA). Serum lipids levels were measured by biochemical methods. Results: The serum levels of MMP-2, MMP-9, ox-LDL were significantly higher in H, A and AH groups than those in N group. Those of ox LDL in H, AH groups was higher than that of in A group. The serum level of MMP-2, MMP-9 in AH groups were higher than that of in H group. The score of mini-mental state examination (MMSE) in A and AD groups was negatively correlated with the serum level of ox-LDL. Relationship between the score of MMSE and the serum level of ox-LDL in AD groups and non-AD groups had statistical significance. Conclusion: MMP-2, MMP-9, ox-LDL and abnormal lipid metabolism may participate in pathogenesis of AD, in which abnormal lipid metabolism induces expressions of MMP-2,MMP-9 and ox-LDL. Oxidative stress and blood-brain barrier disruption might accelerate the process of AD.

  4. The Biological Behaviors of Rat Dermal Fibroblasts Can Be Inhibited by High Levels of MMP9

    Directory of Open Access Journals (Sweden)

    Sheng-Neng Xue

    2012-01-01

    Full Text Available Aims. To explore the effects of the high expression of MMP9 on biological behaviors of fibroblasts. Methods. High glucose and hyperhomocysteine were used to induce MMP9 expression in skin fibroblasts. Cell proliferation was detected by flow cytometry and cell viability by CCK-8. ELISA assay was used to detect collagen (hydroxyproline secretion. Scratch test was employed to evaluate horizontal migration of cells and transwell method to evaluate vertical migration of cells. Results. The mRNA and protein expressions of MMP9 and its protease activity were significantly higher in cells treated with high glucose and hyperhomocysteine than those in control group. At the same time, the S-phase cell ratio, proliferation index, cell viability, collagen (hydroxyproline secretion, horizontal migration rate, and the number of vertical migration cells decreased in high-glucose and hyperhomocysteine-treated group. Tissue inhibitor of metalloproteinase 1 (TIMP1, which inhibits the activity of MMP9, recovered the above biological behaviors. Conclusions. High expression of MMP9 in skin fibroblasts could be induced by cultureing in high glucose and hyperhomocysteine medium, which inhibited cell biological behaviors. Inhibitions could be reversed by TIMP1. The findings suggested that MMP9 deters the healing of diabetic foot ulcers by inhibiting the biological behaviors of fibroblasts.

  5. Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Reis Sabrina

    2012-06-01

    Full Text Available Abstract Background Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC. Methods MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003. Invasive tumors (pT1-pT2 had higher expression levels of MMP-9 than superficial tumors (pTa (p = 0.026. The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048. Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003 and IL-8 (p = 0.005. Conclusion We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

  6. Interplay Between MMP-9 and TIMP-2 Regulates Ameloblastoma Behavior and Tooth Morphogenesis.

    Science.gov (United States)

    Nunia, Kalpana; Urs, Aadithya B; Kumar, Priya

    2016-01-01

    Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been implicated in the local invasiveness of ameloblastoma. This study aims to assess the role of MMP-9 and TIMP-2 in regulating tumor progression in ameloblastomas, taking tooth germs as control. Formalin-fixed, paraffin-embedded tissue sections of 4 tooth germs and 32 ameloblastomas were immunohistochemically examined using antibodies against MMP-9 and TIMP-2. Strong MMP-9 positivity was seen in the epithelial component in both controls and solid multicystic ameloblastoma. Statistically significant difference was observed in the mean stromal MMP-9 immunoscores between follicular, acanthomatous, and granular ameloblastoma when compared with the tooth germ (P=0.004). TIMP-2 expression in the epithelial and mesenchymal components of solid multicystic ameloblastoma and tooth germ was weak as compared with MMP-9 expression. Highest mean epithelial TIMP-2 immunoscore was observed in follicular ameloblastoma and the difference was statistically significant between follicular and granular ameloblastoma (P=0.05). The comparison of mean stromal TIMP-2 immunoscores showed statistically significant difference between follicular subtype and tooth germ (P=0.048), with tooth germ showing least expression among the groups studied. Strong stromal expression of MMP-9 in ameloblastoma compared with tooth germ mesenchyme indicated the possibility of tumor induction with release of growth factors and cytokines, resulting in invasiveness of ameloblastoma. Epithelial TIMP-2 expression was associated with the least and most aggressive behavior of follicular and granular cell ameloblastoma, respectively. Stromal TIMP-2 expression reflected its role in regulating tumor progression in ameloblastoma and in regulating developmental processes in tooth germs by their inhibitory effect on MMP-9.

  7. Coexpression of CXCR4 and MMP9 predicts lung metastasis and poor prognosis in resected osteosarcoma.

    Science.gov (United States)

    Ren, Zhiwu; Liang, Shoulei; Yang, Jilong; Han, Xiuxin; Shan, Luling; Wang, Biying; Mu, Tianyang; Zhang, Yanqin; Yang, Xueli; Xiong, Shunbin; Wang, Guowen

    2016-04-01

    Osteosarcoma is a highly aggressive bone disease with a tendency to metastasize to the lung. The 5-year survival of patients with metastatic osteosarcoma is only 20 %. Many studies have demonstrated SDF-1/CXCR4 and MMP9 play important roles in the metastasis of malignant tumors, including osteosarcoma. The aim of this study was to investigate the association of CXCR4 and MMP9 expression with clinicopathological features and pulmonary metastasis in osteosarcoma. Using tumor tissue microarrays, we analyzed the expression of CXCR4 and MMP9 among 34 primary osteosarcomas with pulmonary metastasis and 62 primary osteosarcomas without metastasis. A median time of 57.5 months (range: 6 to 171 months) follow-up was performed to evaluate tumor metastasis and the patient survival. The prognostic values were determined by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. The accuracy of oncologic outcome prediction was evaluated by receiver-operating characteristics (ROC) curves (AUC). The expression of CXCR4 and MMP9 was significantly correlated in tumor tissues (P = 0.026). Both CXCR4 and MMP9 were independent predictors for overall survival and metastasis-free survival by Cox multivariate analysis, and high expression for both CXCR4 and MMP9 were even more significant and better biomarkers for osteosarcoma metastasis and survival. The combination of CXCR4 and MMP9 high expression is very likely to be a valuable independent predictor of lung metastasis and survival in osteosarcoma patients.

  8. Expression of MMP-9, AECA and ANCA in peripheral blood of patients with Kawasaki disease and its relationship with coronary artery lesions%MMP-9、AECA、ANCA 蛋白在川崎病外周血的表达及其与冠状动脉损害的关系

    Institute of Scientific and Technical Information of China (English)

    王晓华; 王倩; 赵建美

    2016-01-01

    Objective To investigate the potential role and clinical significance of matrix metalloproteinase 9 ( MMP-9), anti-endothelial cell antibodies (AECA) and anti-neutrophil cytoplasmic antibodies (ANCA) in vasculitis and coro-nary artery lesions ( CAL) of patients with Kawasaki disease ( KD) .Methods Forty-two children with KD were divided into two groups:CAL group (n=16) and non-coronary artery lesion (NCAL) group (n=26).Twenty febrile children and 15 children for selective operation were chosen as the control group.Serum levels of MMP-9, AECA and ANCA were meas-ured by enzyme-linked immunosorbent assay ( ELISA) , fluorescence quantitative-PCR and gelatin zymography were respec-tively used to detect MMP-9 mRNA expression and enzyme activity.Results The MMP-9 mRNA expression, protein level and enzymatic activity in the acute phase of KD patients were all higher than those in the two control groups ( all P<0.01), and they were significantly higher in the CAL group than in the NCAL group (all P<0.05).Moreover, MMP-9 mRNA expression, enzymatic activity and protein level were decreased significantly in the remission phase (all P<0.01). Serum AECA and ANCA protein levels of KD patients in the acute phase were significantly higher as compared with those of the two control groups (all P<0.01).The protein level of ANCA in the CAL group was significantly higher than that of the NCAL group (P<0.01).There was a positive correlation between serum MMP-9 and AECA protein in the acute phase of KD (r=0.77, P<0.01).The serum MMP-9 and ANCA protein levels of the CAL group in the acute phase were both positively correlated with LCA/AAO ratio (r=0.57, P<0.05;r=0.88, P<0.01).Conclusions MMP-9, AECA and ANCA are potential pathological factors in the formation of KD vasculitis and CAL.The serum level detection has a certain value for early prediction of CAL.%目的:探讨基质金属蛋白酶-9(MMP-9)、抗内皮细胞抗体(AECA)和抗中性粒细胞胞

  9. Inflammageing assessed by MMP9 in normal Japanese individuals and the patients with Werner syndrome.

    Science.gov (United States)

    Goto, Makoto; Chiba, Junji; Matsuura, Masaaki; Iwaki-Egawa, Sachiko; Watanabe, Yasuhiro

    2016-05-01

    Age-associated minor inflammation: inflammageing may explain human ageing mechanism(s). Our previous study reported a significant increase in the serum level of highly sensitive C-reactive protein (hsCRP) with normal ageing and the patients with Werner syndrome (WS). To further study the minor inflammatory condition associated with ageing, another possible ageing biomarker: matrix metalloproteinase-9 (MMP9) was examined in the sera from 217 normal Japanese individuals aged between 1 and 100 years and 41 mutation-proven Japanese WS aged between 32 and 70 years. MMP9 was assayed by ELISA. The serum level of MMP9 was elevated significantly (p normal ageing from both sexes as hsCRP. In contrast to normal ageing, the serum MMP9 level in WS decreased significantly with calendar age (p normal adult population aged between 25 and 70 years (109.1 ± 9.4), nor normal elderly population aged between 71 and 100 years (179.9 ± 16.1). Although both normal ageing and WS were associated with minor inflammation, the inflammatory parameters such as serum MMP9 and hsCRP changed differently between normal ageing and WS. The WS-specific chronic inflammation including skin ulcer and diabetes mellitus may contribute the different behavior of both ageing biomarkers from normal ageing.

  10. Serum matrix metalloproteinase 9 (MMP9) as a biochemical marker for wasting marmoset syndrome.

    Science.gov (United States)

    Yoshimoto, Takuro; Niimi, Kimie; Takahashi, Eiki

    2016-06-01

    Use of the common marmoset (Callithrix jacchus) as a non-human primate experimental animal has increased in recent years. Although wasting marmoset syndrome (WMS) is one of the biggest problems in captive marmoset colonies, the molecular mechanisms, biochemical markers for accurate diagnosis and a reliable treatment remain unknown. In this study, as a first step to finding biochemical marker(s) for the accurate diagnosis of WMS, we conducted blood cell counts, including hematocrit, hemoglobin and platelets, and examined serum chemistry values, including albumin, calcium and levels of serum matrix metalloproteinase 9 (MMP9), using a colony of marmosets with and without weight loss. MMP9 is thought to be an enzyme responsible for the degradation of extracellular matrix components and participates in the pathogenesis of inflammatory conditions, such as human and murine inflammatory bowel disease, which, like WMS, are characterized histologically by inflammatory cell infiltrations in the intestines. The values of hematocrit and hemoglobin and levels of serum albumin and calcium in the WMS group were significantly decreased versus the control group. The platelet values and serum MMP9 concentrations were increased significantly in the WMS group compared with the control group. MMP9 could be a new and useful marker for the diagnosis of WMS in addition to hematocrit, hemoglobin, serum albumin and calcium. Our results also indicate that MMP9 could be a useful molecular candidate for treatment.

  11. Dihydroavenanthramide D inhibits human breast cancer cell invasion through suppression of MMP-9 expression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young-Rae; Noh, Eun-Mi; Oh, Hyun Ju; Hur, Hyun; Kim, Jeong-Mi; Han, Ji-Hey; Hwang, Jin-Ki; Park, Byung-Hyun; Park, Jin-Woo [Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of); Youn, Hyun Jo; Jung, Sung Hoo [Department of Surgery, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of); Kim, Byeong-Soo; Jung, Ji-Youn; Lee, Sung-Ho [Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702 (Korea, Republic of); Park, Chang-Sik [Division of Animal Science and Resources Research Center for Transgenic Cloned Pigs, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Jong-Suk, E-mail: jsukim@jbnu.ac.kr [Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of)

    2011-02-25

    Research highlights: {yields} MMP-9 plays a pivotal role in the invasion of MCF-7 breast cancer cells. {yields} TPA stimulates MMP-9 expression through activation of MAPK/NF-{kappa}B and MAPK/AP-1 pathways. {yields} Dihydroavenanthramide D suppresses MMP-9 expression via inhibition of TPA-induced MAPK/NF-{kappa}B and MAPK/AP-1 activations. {yields} Dihydroavenanthramide D blocks cell invasion of MCF-7 breast cancer cells. -- Abstract: Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-{kappa}B), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-{kappa}B) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-{kappa}B and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.

  12. Suppressed MMP-9 Activity in Myocardial Infarction-Related Cardiogenic Shock Implies Diminished Rage Degradation.

    Science.gov (United States)

    Selejan, Simina-Ramona; Hewera, Lisa; Hohl, Matthias; Kazakov, Andrey; Ewen, Sebastian; Kindermann, Ingrid; Böhm, Michael; Link, Andreas

    2017-07-01

    Receptor for advanced glycation end products (RAGE) and its cleavage fragment soluble RAGE (sRAGE) are opposite players in inflammation. Enhanced monocytic RAGE expression and decreased plasma sRAGE levels are associated with higher mortality in infarction-related cardiogenic shock. Active matrix metalloproteinase-9 (MMP-9) has been implied in RAGE ectodomain cleavage and subsequently sRAGE shedding in vitro. We investigated MMP-9 activity in myocardial infarction-induced cardiogenic shock with regard to RAGE/sRAGE regulation. We determined MMP-9 serum activity by zymography and tissue inhibitor of matrix metalloproteinases (TIMP-1) expression by Western blot and correlated it to RAGE/sRAGE data in patients with cardiogenic shock after acute myocardial infarction (CS, n = 30), in patients with acute myocardial infarction without shock (AMI, n = 20) and in healthy volunteers (n = 20).MMP-9 activity is increased in AMI (P = 0.02 versus controls), but significantly decreased in CS with lowest levels in non-survivors (n = 13, P = 0.02 versus AMI). In all patients, MMP-9 activity correlated inversely with RAGE expression on circulating monocytes (r = -0.57; P = 0.0001; n = 50).TIMP-1 levels showed an inverse regulation in comparison to active MMP-9 with significantly decreased levels in AMI as compared with controls (P = 0.02 versus controls) and highest levels in non-survivors of CS (P RAGE-induced deleterious inflammation in cardiogenic shock.

  13. ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions

    Science.gov (United States)

    Hsieh, Wen-Yeh; Kuan, Tang-Ching; Cheng, Kun-Shan; Liao, Yan-Chiou; Chen, Mu-Yuan; Lin, Pei-Heng; Hsu, Yuan-Chang; Huang, Chen-Yi; Hsu, Wei-Hua; Yu, Sheng-Yao; Lin, Chih-Sheng

    2012-01-01

    Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates. Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28). Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions. Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy. PMID:23091417

  14. Characterization of quenched fluorescent triple helical peptides for MMP-2 and MMP-9 optical imaging

    Science.gov (United States)

    Cheney, Philip P.; Fields, Gregg B.; Achilefu, Samuel; Edwards, W. Barry

    2009-02-01

    The prevalence of the gelatinases, MMP-2 and MMP-9, in many human tumors, including breast, colorectal, prostate and gastric cancer, make them an attractive target for molecular imaging. A self assembling homotrimeric triple helical peptide (THP), incorporating sequences from type V collagen with high specificity to MMP-2 and MMP-9, was previously developed. To investigate the viability of a THP for gelatinase imaging, we conjugated 5FAM to ..-amino groups of lysine flanking the hydrolysis site and subjected this substrate (THP-5FAM) to vitro analysis. The synthesis and in vitro results was presented.

  15. Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade.

    Science.gov (United States)

    Hathaway, Catherine K; Grant, Ruriko; Hagaman, John R; Hiller, Sylvia; Li, Feng; Xu, Longquan; Chang, Albert S; Madden, Victoria J; Bagnell, C Robert; Rojas, Mauricio; Kim, Hyung-Suk; Wu, Bingruo; Zhou, Bin; Smithies, Oliver; Kakoki, Masao

    2015-04-21

    We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff hearts. Global or cardiomyocyte-specific switching expression from L to H normalized the abnormalities already present in young adult L/L mice. An epithelial sodium channel antagonist normalized plasma volume and blood pressure, but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially improved cardiac function. Genetic absence of Mmp9 also improved cardiac function, but increased superoxide remained. We conclude that endothelin-1 is critical for maintaining normal contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching. Even a modest (∼35%) decrease in endothelin-1 gene (Edn1) expression is sufficient to cause cardiac dysfunction.

  16. MMP-2 and MMP-9 as prognostic factors in ischaemic stroke

    Directory of Open Access Journals (Sweden)

    Justyna Zielińska-Turek

    2016-09-01

    Full Text Available Objectives: No widely available, adequately sensitive diagnostic test to establish prognosis in stroke patients has been developed thus far. The aim of this study was to analyse changes in plasma levels of MMP-9 and MMP-2 as potential prognostic factors in patients with ischaemic stroke. Methods: The study included 56 patients presenting with the signs of ischaemic stroke for less than 24 hours, and 60 healthy controls without a history of neurological and/or inflammatory disorders. Plasma concentrations of MMP-2 and MMP-9 were determined immunoenzymatically at admission (i.e. within 24 hours of the cerebrovascular episode and on the 7th day of hospital stay. Results: Median concentrations of MMP-9 in stroke patients were significantly lower than in the controls, both at admission and on the 7th day of hospital stay. No significant changes in the concentration of MMP-2 in ischaemic stroke patients were observed during the course of hospital stay. No significant association was found between both MMP concentrations and neurological status of patients with cerebrovascular episodes. Conclusions: The lack of significant associations between plasma concentrations of MMP-2/MMP-9 and clinical status suggests that these metalloproteinases should not be used as prognostic factors in patients with ischaemic cerebral episodes.

  17. Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

    NARCIS (Netherlands)

    Kubben, F.J.G.M.; Sier, C.F.M.; Schram, M.; Witte, T.A.M.C.; Veenendaal, R.A.; Duijn, W. van; Verheijen, J.H.; Hanemaaijer, R.; Lamers, C.B.H.W.; Verspaget, H.W.

    2007-01-01

    Background: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. Aim: This study was performed to investigate whether H.

  18. Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline.

    Science.gov (United States)

    Uehara, Osamu; Takimoto, Kousuke; Morikawa, Tetsuro; Harada, Fumiya; Takai, Rie; Adhikari, Bhoj Raj; Itatsu, Ryoko; Nakamura, Tomohisa; Yoshida, Koki; Matsuoka, Hirofumi; Nagayasu, Hiroki; Saito, Ichiro; Muthumala, Malsantha; Chiba, Itsuo; Abiko, Yoshihiro

    2017-07-01

    Betel quid chewing is implicated in the high prevalence of oral cancer in Southeast Asian countries. One of the major components of betel quid is arecoline. In the present study, in order to characterize the association between chronic arecoline stimulation and carcinogenesis the expression level of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated with arecoline was assessed. The HGEPs were alternated between 3 days of incubation with arecoline (50 µg/ml), and 3 days without arecoline, for up to 30 days. The expression levels of the MMPs and TIMPs in the cells stimulated with arecoline were evaluated by reverse transcription-quantitative polymerase chain reaction at 18 and 30 days. The expression of MMP-9 mRNA in the experimental group was significantly increased compared with in the control group (Parecoline. Based on the data, it is hypothesized that MMP-9 activity may be involved in the pathological alterations of oral epithelium induced by betel quid chewing, and that the NF-κB/IκB, MAPK, p38 MAPK and STAT3 signaling pathways may be involved in the production of MMP-9 induced by betel quid chewing.

  19. Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

    NARCIS (Netherlands)

    Kubben, F.J.G.M.; Sier, C.F.M.; Schram, M.; Witte, T.A.M.C.; Veenendaal, R.A.; Duijn, W. van; Verheijen, J.H.; Hanemaaijer, R.; Lamers, C.B.H.W.; Verspaget, H.W.

    2007-01-01

    Background: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. Aim: This study was performed to investigate whether H. p

  20. Deriving a cardiac ageing signature to reveal MMP-9-dependent inflammatory signalling in senescence.

    Science.gov (United States)

    Ma, Yonggang; Chiao, Ying Ann; Clark, Ryan; Flynn, Elizabeth R; Yabluchanskiy, Andriy; Ghasemi, Omid; Zouein, Fouad; Lindsey, Merry L; Jin, Yu-Fang

    2015-06-01

    Cardiac ageing involves the progressive development of cardiac fibrosis and diastolic dysfunction coordinated by MMP-9. Here, we report a cardiac ageing signature that encompasses macrophage pro-inflammatory signalling in the left ventricle (LV) and distinguishes biological from chronological ageing. Young (6-9 months), middle-aged (12-15 months), old (18-24 months), and senescent (26-34 months) mice of both C57BL/6J wild type (WT) and MMP-9 null were evaluated. Using an identified inflammatory pattern, we were able to define individual mice based on their biological, rather than chronological, age. Bcl6, Ccl24, and Il4 were the strongest inflammatory markers of the cardiac ageing signature. The decline in early-to-late LV filling ratio was most strongly predicted by Bcl6, Il1r1, Ccl24, Crp, and Cxcl13 patterns, whereas LV wall thickness was most predicted by Abcf1, Tollip, Scye1, and Mif patterns. With age, there was a linear increase in cardiac M1 macrophages and a decrease in cardiac M2 macrophages in WT mice; of which, both were prevented by MMP-9 deletion. In vitro, MMP-9 directly activated young macrophage polarization to an M1/M2 mid-transition state. Our results define the cardiac ageing inflammatory signature and assign MMP-9 roles in mediating the inflammaging profile by indirectly and directly modifying macrophage polarization. Our results explain early mechanisms that stimulate ageing-induced cardiac fibrosis and diastolic dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  1. Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting

    Directory of Open Access Journals (Sweden)

    Rongrong Zhang

    2015-01-01

    Full Text Available Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS. Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

  2. OSAHS患者呼出气冷凝液中MMP-9的变化%Changes of MMP-9 in exhaled breath condensate of patients with obstructive sleep apnea hypopnea syndrome

    Institute of Scientific and Technical Information of China (English)

    徐健; 李一禄; 陈济明; 徐晓妮; 何梦颖

    2014-01-01

    Objective To evaluate the changes of matrix metalloproteases-9(MMP-9)in exhaled breath con-densate( EBC) with Obstructive sleep apnea-hypopnea syndrome ( OSAHS) . Methods Select 40 males and OSAHS patients for the experimental group, 30 healthy subjects matched age and body mass index as a control group. exhaled breath condensate The levels of MMP-9 in EBC were determined by ELISA. Results Compared to the control group, the MMP-9 in OSAHS group was significantly higher ( P<0. 05 ) . MMP-9 was positively correlated with AHI ( P<0. 05), and negative correlated the lowest SaO2(P<0. 05). Conclusion The MMP-9 levels in EBC in OSAHS pa-tients may reflect the severity of OSAHS.%目的:观察阻塞性睡眠呼吸暂停低通气综合征( OSAHS)患者呼出气冷凝液( EBC)中基质金属蛋白酶9(MMP-9)的变化。方法选取男性40例OSAHS患者为实验组,30例年龄、体重指数等均相匹配的健康查体者为对照组,用ELISA检测EBC中MMP-9水平。结果和对照组比较,OSAHS组EBC中MMP-9明显升高,有显著统计学意义(P<0.05)。 MMP-9与AHI呈正相关,与最低SaO2负相关(P均<0.05)。结论OSAHS患者EBC中MMP-9水平可反映OSAHS病情的严重程度。

  3. 骨肉瘤组织中MMP-2、MMP-9的表达及意义

    Institute of Scientific and Technical Information of China (English)

    周钱宏; 刘爱东

    2009-01-01

    目的 探讨骨肉瘤中基质金属蛋白酶(MMP)-2及MMP-9的表达及其在骨肉瘤发生、发展中的作用.方法 采用免疫组织化学技术检测46例骨肉瘤组织及12例良性骨肿瘤组织中MMP-2及MMP-9的表达情况.结果 MMP-2及MMP-9在骨肉瘤中的表达量明显高于良性骨肿瘤组织,MMP-2及MMP-9的表达与Ennecking分期有关.结论 MMP-2及MMP-9可作为预测骨肉瘤预后的重要指标.

  4. Inhibition of MMP-9 by green tea catechins and prediction of their interaction by molecular docking analysis.

    Science.gov (United States)

    Sarkar, Jaganmay; Nandy, Suman Kumar; Chowdhury, Animesh; Chakraborti, Tapati; Chakraborti, Sajal

    2016-12-01

    Green tea polyphenolic catechins have been shown to prevent various types of diseases such as pulmonary hypertension (PAH), cancer and cardiac and neurological disorders. Matrix metalloproteinases (MMPs) play an important role in the development of PAH. The present study demonstrated that among the four green tea catechins (EGCG, ECG, EC and EGC), EGCG and ECG inhibit pro-/active MMP-9 activities in pulmonary artery smooth muscle cell culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-9 with the green tea catechins by computational methods. In silico molecular docking analysis revealed a strong interaction between pro-/active MMP-9 and EGCG/ECG, and galloyl group appears to be responsible for this enhanced interaction. The molecular docking studies corroborate our experimental observation that EGCG and ECG are mainly active in preventing both the proMMP-9 and MMP-9 activities.

  5. Correlation between the severity of coronary artery lesions and levels of estrogen, hs-CRP and MMP-9.

    Science.gov (United States)

    Guo, Changlei; Zhang, Shaoli; Zhang, Junbiao; Liu, Hui; Li, Peicheng; Liu, Hengdao; Wang, Yakun

    2014-05-01

    The aim of this study was to investigate the correlation between the severity of coronary artery lesions in patients with acute coronary syndromes (ACS) and levels of estrogen, high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). A total of 65 patients with ACS, 33 patients with stable angina pectoris (SAP) and 36 healthy controls were randomly enrolled. Patients with ACS were subdivided into two groups: Acute myocardial infarction (AMI; n=30) and unstable angina pectoris (UAP; n=35). Serum levels of estrogen, hs-CRP and MMP-9 were detected in the four groups of subjects. Serum estrogen levels in patients with AMI, UAP and SAP were significantly lower than those in the control group (Phs-CRP and MMP-9, followed in descending order by those with UAP and SAP (Phs-CRP and MMP-9 were also significantly different among the AMI, UAP and SAP groups (Phs-CRP and MMP-9 levels (r=-0.6634 and -0.6878, respectively; both Phs-CRP and MMP-9 levels correlated positively (r=0.7208, Phs-CRP and MMP-9 levels (r=0.6519 and 0.6835, respectively; both Phs-CRP and MMP-9 levels were significantly correlated with the severity of coronary artery lesions. There was also a significant correlation between serum estrogen, hs-CRP and MMP-9 levels. These data indicate that serum estrogen, hs-CRP and MMP-9 have the potential to be used as biomarkers for evaluating the severity of coronary artery lesions and the stability of coronary artery plaques.

  6. Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Derek C Marshall

    Full Text Available Expression of matrix metalloproteinase 9 (MMP9 is elevated in a variety of inflammatory and oncology indications, including ulcerative colitis and colorectal cancer. MMP9 is a downstream effector and an upstream mediator of pathways involved in growth and inflammation, and has long been viewed as a promising therapeutic target. However, previous efforts to target matrix metalloproteinases (MMPs, including MMP9, have utilized broad-spectrum or semi-selective inhibitors. While some of these drugs showed signs of efficacy in patients, all MMP-targeted inhibitors have been hampered by dose-limiting toxicity or insufficient clinical benefit, likely due to their lack of specificity. Here, we show that selective inhibition of MMP9 did not induce musculoskeletal syndrome (a characteristic toxicity of pan-MMP inhibitors in a rat model, but did reduce disease severity in a dextran sodium sulfate-induced mouse model of ulcerative colitis. We also found that MMP9 inhibition decreased tumor growth and metastases incidence in a surgical orthotopic xenograft model of colorectal carcinoma, and that inhibition of either tumor- or stroma-derived MMP9 was sufficient to reduce primary tumor growth. Collectively, these data suggest that selective MMP9 inhibition is a promising therapeutic strategy for treatment of inflammatory and oncology indications in which MMP9 is upregulated and is associated with disease pathology, such as ulcerative colitis and colorectal cancer. In addition, we report the development of a potent and highly selective allosteric MMP9 inhibitor, the humanized monoclonal antibody GS-5745, which can be used to evaluate the therapeutic potential of MMP9 inhibition in patients.

  7. MMP-9和 TGFβ1在宫颈鳞癌中的表达和意义%The expression and significance of matrixmetalloproteinase-9 (MMP-9) andtransforming growth factorβ1 (TGF-βl) incervical cancer Abstract

    Institute of Scientific and Technical Information of China (English)

    沈浩明; 杨友义; 吴白平; 向延娥

    2015-01-01

    目的:分别检测宫颈分泌物、血液和宫颈病变组织中的基质金属蛋白酶-9(MMP-9)和转化生长因子β1(TGF-βl)的表达情况,探讨其在宫颈病变形成及演进过程中的意义。方法:应用 ELISA 法检测66例病人(其中慢性宫颈炎组织10例、CINcervicalintraepithelialneoplasia 宫颈上皮内瘤变24例,宫颈鳞癌32例)的宫颈分泌物和血清中的 TGF-βl 和 MMP-9的表达水平。应用免疫组织化学 SP 法检测相对应病人石蜡包埋的不同病变宫颈组织中TGF-βl 和 MMP-9的表达。结果:1.在血清和宫颈分泌物中 TGF-βl 和 MMP-9的浓度与宫颈癌密切相关:慢性宫颈炎组、宫颈上皮内瘤变(CIN)组和宫颈鳞癌(CxCa)组的样本中 TGF-βl 和 MMP-9的浓度逐级升高,提示随着宫颈癌恶性程度的增加,TGF-βl 和 MMP-9的表达明显增强。血清和宫颈分泌物中 MMP-9和 TGF-β1与其切片免疫组化结果相吻合。随着 MMP-9在宫颈分泌物和血清中表达的增强,TGF-β1的表达也明显增高,两者呈正相关。2.TGF-βl 和 MMP-9表达与宫颈癌的病理和临床分类的关系:在宫颈癌组织中有淋巴结转移的 MMP-9和 TGFβ1的表达阳性率显著高于无淋巴结转移的。在宫颈癌≥Ⅱ b 期的 MMP-9和 TGF-βl 的表达阳性率显著高于≤Ⅱ a 期的。MMP-9和 TGF-βl 与宫颈癌肿瘤的大小和组织病理学分级无显著性差异。结论:TGF-βl 和 MMP-9在宫颈病变、宫颈分泌物和血清的中表达与病变良恶性有关,TGF-βl 和 MMP-9高表达是宫颈恶性肿瘤的表现之一,并且 TGF-βl和 MMP-9在宫颈分泌物或血清中的表达具有显著相关性。%Objesctive The expression of matrix metalloproteinase-9 (MMP-9) and transforming growth factorβ1 (TGF-βl) were detectedin cervical secretions, blood andcervical lesions, in order to investigate the significance in thedevelopment ofcervical lesions. Methods 66 cases (including 10

  8. ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer.

    Science.gov (United States)

    Lin, Li-Fang; Chuang, Chih-Hung; Li, Chien-Feng; Liao, Ching-Chun; Cheng, Chun-Pei; Cheng, Tian-Lu; Shen, Meng-Ru; Tseng, Joseph T; Chang, Wen-Chang; Lee, Wen-Hwa; Wang, Ju-Ming

    2010-01-01

    The BRCA1-interacted transcriptional repressor ZBRK1 has been associated with antiangiogenesis, but direct evidence of a tumor suppressor role has been lacking. In this study, we provide evidence of such a role in cervical carcinoma. ZBRK1 levels in cervical tumor cells were significantly lower than in normal cervical epithelial cells. In HeLa cervical cancer cells, enforced expression inhibited malignant growth, invasion, and metastasis in a variety of in vitro and in vivo assays. Expression of the metalloproteinase MMP9, which is known to be an important driver of invasion and metastasis, was found to be inversely correlated with ZBRK1 in tumor tissues and a target for repression in tumor cells. Our findings suggest that ZBRK1 acts to inhibit metastasis of cervical carcinoma, perhaps by modulating MMP9 expression.

  9. Angiogenesis in vestibular schwannomas: expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Werther, Kim; Nalla, Amarnadh;

    2010-01-01

    Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. It has been demonstrated that vestibular schwannoma VEGF expression correlates with tumor growth pattern, whereas knowledge on the expression of MMPs is lacking. This study t...... targets the angiogenic process by investigation of tumor expression of MMP-2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1. A possible correlation with gender, patient age, symptom duration, tumor size, and the absolute and relative growth rate is explored....

  10. MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation

    Directory of Open Access Journals (Sweden)

    Donaldson GC

    2005-12-01

    Full Text Available Abstract Background Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood. This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation. Methods Nineteen COPD patients ((median, [IQR] age 69 [63 to 74], forced expiratory volume in one second (FEV1 1.0 [0.9 to1.2], FEV1% predicted 37.6 [27.3 to 46.2] provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand. Results MMP-9 levels increased from 10.5 μg/g [1.2 to 21.1] prior to exacerbation to 17.1 μg/g [9.3 to 48.7] during exacerbation (P P = 0.16. MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P P P Conclusion During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline.

  11. Matrix metalloproteinase 9 (MMP-9) in osteosarcoma: review and meta-analysis.

    Science.gov (United States)

    Wang, Jing; Shi, Qiong; Yuan, Tai-Xian; Song, Qi-Lin; Zhang, Yan; Wei, Qiang; Zhou, Lan; Luo, Jinyong; Zuo, Guowei; Tang, Min; He, Tong-Chuan; Weng, Yaguang

    2014-06-10

    The aim of this study is to determine the value of matrix metalloproteinase 9 (MMP-9) in diagnosis of osteosarcoma (OS). A systematic review and meta-analysis was conducted using MEDLINE, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, China Biomedical literature Database (CBM) and China National Knowledge Internet (CNKI) from inception through Aug 29, 2013. Articles written in English or Chinese that investigated the accuracy of MMP-9 for the diagnosis of OS were included. Pooled sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) were determined. I(2) was used to test heterogeneity and source of heterogeneity was investigated by meta-regression (tested with Meta-DiSc and STATA 12.0 statistical softwares). A total of 3729 articles were retrieved, of which 18 were included, accounting for 892 patients. Overall, the pooled sensitivity, specificity and AUC were 0.78 (95% CI 0.730-0.83), 0.90 (95% CI 0.79-0.95), and 0.87 (95% CI 0.83-0.89), respectively. The studies had substantial heterogeneity (I(2)=84%, 95% CI 65-100) (96%, 95% CI 94-99). Assay kit subgroup was the main source of the heterogeneity. Although MMP-9 was identified as a potential biomarker for OS, more studies were clearly needed to establish its diagnostic value.

  12. Modafinil treatment prevents REM sleep deprivation-induced brain function impairment by increasing MMP-9 expression.

    Science.gov (United States)

    He, Bin; Peng, Hua; Zhao, Ying; Zhou, Hui; Zhao, Zhongxin

    2011-12-01

    Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats.

  13. MicroRNA-3713 regulates bladder cell invasion via MMP9.

    Science.gov (United States)

    Wu, Wen-Bo; Wang, Wei; Du, Yi-Heng; Li, Hao; Xia, Shu-Jie; Liu, Hai-Tao

    2016-08-31

    Transitional cell carcinoma (TCC) is the most common type of bladder cancer but its carcinogenesis remains not completely elucidated. Dysregulation of microRNAs (miRNAs) is well known to be involved in the development of various cancers, including TCC, whereas a role of miR-3713 in the pathogenesis of TCC has not been appreciated. Here, we reported that significantly higher levels of matrix metallopeptidase 9 (MMP9), and significantly lower levels of miR-3713 were detected in TCC tissue, compared to the adjacent non-tumor tissue, and were inversely correlated. Moreover, the low miR-3713 levels in TCC specimens were associated with poor survival of the patients. In vitro, overexpression of miR-3713 significantly decreased cell invasion, and depletion of miR-3713 increased cell invasion in TCC cells. The effects of miR-3713 on TCC cell growth appeared to result from its modification of MMP9 levels, in which miR-3713 was found to bind to the 3'-UTR of MMP9 mRNA to inhibit its protein translation in TCC cells. This study highlights miR-3713 as a previously unrecognized factor that controls TCC invasiveness, which may be important for developing innovative therapeutic targets for TCC treatment.

  14. Eugenol with antioxidant activity inhibits MMP-9 related to metastasis in human fibrosarcoma cells.

    Science.gov (United States)

    Nam, Hyang; Kim, Moon-Moo

    2013-05-01

    The oxidative damage of lipid, protein and DNA is known to be involved in chronic inflammation as well as metastasis. It has been highlighted for searching natural compounds without toxicity to prevent development of these diseases. Thus, it was investigated whether eugenol can inhibit matrix metalloproteinase (MMP) expression and activity as well as antioxidant effect. Eugenol was contained as a major ingredient in herbs such as clove and Magnoliae Flos. The direct scavenging effects of eugenol on DPPH radical, hydrogen peroxide, reducing power, lipid peroxidation and genomic DNA damage related to oxidative stress were evaluated in cell free system. It was observed that eugenol specifically exhibited higher inhibitory effect on hydrogen peroxide than other reactive oxygen species, and also blocked DNA oxidation and lipid peroxidation induced by hydroxyl radical. In addition, the inhibitory effects of eugenol on the activity and expression of MMP-9 activity related to metastasis were determined using gelatin zymography and western-blot. The data showed that it inhibited MMP-9 activities in PMA-stimulated HT1080 cells. Furthermore, it was found that eugenol exerts inhibitory effects on MMP-9 via inactivation of ERK. Therefore, these results suggest that eugenol could be available as an excellent agent for prevention of metastasis related to oxidative stress.

  15. Phosphorylation of FOXP3 by LCK downregulates MMP9 expression and represses cell invasion.

    Directory of Open Access Journals (Sweden)

    Kumiko Nakahira

    Full Text Available Forkhead Box P3 (FOXP3 is a member of the forkhead/winged helix family of the transcription factors and plays an important role not only as a master gene in T-regulatory cells, but also as a tumor suppressor. In this study, we identified lymphocyte-specific protein tyrosine kinase (LCK, which correlates with cancer malignancy, as a binding partner of FOXP3. FOXP3 downregulated LCK-induced MMP9, SKP2, and VEGF-A expression. We observed that LCK phosphorylated Tyr-342 of FOXP3 by immunoprecipitation and in vitro kinase assay, and the replacement of Tyr-342 with phenylalanine (Y342F abolished the ability to suppress MMP9 expression. Although FOXP3 decreased the invasive ability induced by LCK in MCF-7 cells, Y342F mutation in FOXP3 diminished this suppressive effect. Thus we demonstrate for the first time that LCK upregulates FOXP3 by tyrosine phosphorylation, resulting in decreased MMP9, SKP2, and VEGF-A expression, and suppressed cellular invasion. We consider that further clarification of transcriptional mechanism of FOXP3 may facilitate the development of novel therapeutic approaches to suppress cancer malignancy.

  16. Clinical Significance of Urinary Kidney Injury Molecule-1,Serum Cystatin C and Urinary Neutrophil Gelatinase-associated Lipocalin in the Prediction of Early Kidney Damage in Preeclampsia%尿肾损伤分子1、血清胱抑素C和尿中性粒细胞明胶酶相关性脂质运载蛋白预测子痫前期发病和早期肾损伤的价值

    Institute of Scientific and Technical Information of China (English)

    黄菁; 郑美玲; 王玉珏; 于庭

    2016-01-01

    目的:探讨新型生物学标志物尿肾损伤分子1(KIM⁃1)、血清胱抑素C和尿中性粒细胞明胶酶相关性脂质运载蛋白(NGAL)与子痫前期的关系及预测子痫前期发病和早期肾损伤的价值。方法选择2014年10月至2015年7月在吉林大学第二医院住院的30例重度子痫前期孕妇、30例轻度子痫前期孕妇作为子痫前期组,并选取同期住院足月分娩的60例健康孕妇作为对照组。采用ELISA法测定尿KIM⁃1和尿NGAL,采用免疫浊度法测定血清胱抑素C。结果子痫前期组孕妇的尿KIM⁃1、尿NGAL、血清胱抑素C水平明显高于对照组(均P<0.05),随着病情进展各指标均逐渐升高。体质量指数(BMI)、肾小球滤过率(eGFR)、尿蛋白/肌酐比值、尿KIM⁃1、血清胱抑素C和尿NGAL是子痫前期发生的危险因素;尿KIM⁃1、血清胱抑素C、尿NGAL及联合预测因子作为子痫前期早期肾损伤筛查指标的灵敏度分别为83.3%、75.0%、88.9%、96.8%;特异度分别为72.7%、70.0%、75.6%、86.4%。结论尿KIM⁃1、血清胱抑素C和尿NGAL的水平可反映子痫前期的病情进展和子痫前期肾损伤的程度。尿KIM⁃1、血清胱抑素C、尿NGAL联合检测对子痫前期早期肾损伤有更高的预测价值。%Objective To investigate the relationship between serum cystain C,urinary neutrophil gelatinase⁃associated lipocalin(NGAL),uri⁃nary kidney injury molecule⁃1(KIM⁃1)and preeclampsia,and explore the value in predicting preeclampsia and early kidney damage. Methods A total of 30 cases of pregnant women with severe preeclampsia,30 cases of mild preeclampsia and 60 cases of healthy pregnant women admitted in the Second Hospital of Jilin University from October 2014 to July 2015 were enrolled for the study. ELISA was performed to check urinary KIM⁃1 and urinary NGAL,and the serum cystatin C was detected by immune turbidity method. Results KIM⁃1,NGAL,serum cystatin C

  17. The Expression and Significance of HGF and MMP-9 in Lichen Planus%HGF和MMP-9在扁平苔藓皮损中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    何肖; 白莉

    2011-01-01

    目的 检测扁平苔藓皮损中肝细胞生长因子(HGF)和基质金属蛋白酶-9(MMP-9)的表达情况,探讨其在扁平苔藓发病中的意义.方法 应用免疫组化法和RT-PCR法测定30例扁平苔藓及30例正常皮肤组织中HGF和MMP-9的表达水平.结果 扁平苔藓组中HGF和MMP-9的表达率均高于正常对照组(P<0.01),且二者在扁平苔藓皮损中的表达呈正相关(r1=0.391,P1=0.032;r2=0.375,P2=0.041).结论 HGF和MMP-9的高表达可能参与了扁平苔藓的发病.%Objective To explore the expression of hepatocyte growth factor( HGF ) and metalloproteinase - 9( MMP - 9 ) in lichen planus,and investigate the function in pathogenesis of lichen planus.Methods The expression of HGF and MMP - 9 was assayed by RT - PCR and immunohistochemistry in 30 LP lesions and 30 normal skins.Results The expression of HGF and MMP - 9 in LP lesions was stronger than that in normal skins( P <0.01 ),and HGF was positively related to the expression of MMP -9 in LP lesions ( r1 =0.391 ,P1 = 0.032; r2 = 0.375, P2 = 0.041 ).Conclusion The increased expression of HGF and MMP -9 may contribute to the formation and progression of lichen planus.

  18. Expression and significance of Twist、MMP-2 and MMP -9 in breast cancer%乳腺癌组织中Twist、MMP-2和MMP-9的表达及意义

    Institute of Scientific and Technical Information of China (English)

    艾斯卡尔·阿尤甫; 古力米热·布然江; 欧江华

    2012-01-01

    Objective To investigate the expression and significance of Twist, MMP - 2 and MMP -9 in Breast Cancer . Methods Immunohislochemical SP method was used to examine the levels of Twist protein, MMP - 2, MMP - 9 in Breast Cancer (70 cases) and paracancerous normal tissues (35 cases) . Results The positive rates of Twist, MMP - 2 and MMP - 9 were higher in Breast Cancer than thouse in the tumor - adjacent normal tissues (72. 9% ,55.1% ,67. 1% vs 16.7% ,28. 6% ,37. 1% ,P < 0.05). Their expressions were positively correlated with the tumor differentiation, the depth of invasion lymph node metastasis (P < 0. 05). Expression of MMP - 2 was positively correlated with that of MMP - 9 (P <0.05). Conclusions The aberrant expressions of Twist,MMP -2 and MMP -9 may play a cooperative role in the infiltration and metastasis of Breast Cancer, which may be taken as a reference index for e-valuating the metastasis and prognosis.%目的 探讨乳腺癌组织中Twist、MMP -2和MMP -9表达的相关性.方法 采用SP免疫组化法检测70例乳腺癌组织(35例癌旁组织作为对照)中Twist、MMP -2和MMP -9的表达情况.结果 乳腺癌组织中Twist、MMP -2和MMP-9的阳性表达率分别为72.9%、55.7%和67.1%,均显著高于癌旁正常组织中的16.7%、28.6%和37.10%(P<0.05).Twist、MMP -2和MMP-9与肿瘤的分化程度、浸润深度和淋巴结转移有关(P<0.05).Twist的表达与MMP -2和MMP -9的表达呈正相关.MMP -2的表达与MMP -9的表达呈正相关.结论 Twist、MMP -2和MMP -9在肿瘤细胞发生浸润转移中有协同作用,可作为评估乳腺癌转移及预后的参考指标.

  19. Expression of MMP-2 and MMP-9 in Cutaneous Malignant Melanoma and its Significance%MMP-2和MMP-9在皮肤恶性黑色素瘤中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    宋宁静; 王晓楠; 陈佳; 吴正升; 章楚光

    2011-01-01

    目的 研究明胶酶(MMP-2和MMP-9)在皮肤黑色素瘤和色素痣组织中的蛋白表达及其意义.方法 应用免疫组织化学S-P法检测90例皮肤黑色素瘤和43例皮肤色素痣组织MMP-2和MMP-9的表达情况,分析它们与患者临床病理特征的关系.结果 皮肤黑色素瘤组织MMP-2和MMP-9蛋白表达阳性率分别为50.0%和55.6%,显著高于色素痣的阳性率27.9%和25.6%(P<0.05和P<0.01);黑色素瘤MMP-2和MMP-9蛋白表达均与肿瘤的浸润深度和淋巴结转移呈正相关(均P<0.05).结论 皮肤恶性黑色素瘤MMP-2和MMP-9表达状况与肿瘤侵袭、转移呈密切相关,提示MMP-2和MMP-9可能在黑色素瘤发生发展过程中发挥了重要作用.%Objective To investigate the expression of MMP-2 and MMP-9 protein in cutaneous melanoma and its significance.Methods The expression of MMP-2 and MMP-9 protein was detected in 90 cases of melanoma and 47 cases of nevus by using streptavidin-peroxidase technique. Their correlations with the clinicopathological features were analyzed. Results The positive rates of MMP-2 and MMP-9 protein in the melanomas were 50.0% and 55.6% ,which were significantly higher than those in the nevus. Both t MMP-2 and MMP-9 protein was positively correlated to the depth of tumour invasion and the lymph node metastasis of melanoma( All P < 0.05). Conclusion The expression of MMP-2 and MMP-9 is closely correlated to the tumout invasion and metastasis. The result suggests that MMP-2 and MMP-9 might play an important role in the cutaneous melanoma development and progression.

  20. The expression of HMGB1/MMP9 and its clinical significance in Non-Small Cell Lung Cancer%HMGB1/MMP9在非小细胞肺癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    苏卫民; 毕明宏

    2012-01-01

    Objective To investigate the significance of high mobility group proteinl ( HMCB1 ) and matrix metalloproteinase-9 ( MMP9 ) in the transfering process of Non-Small Cell Lung Caneer through studying their expression levels in human Non-Small Cell Lung Cancer- and the paraoanoerous tissues in order to reveal their roles in the process of the tumors invasion and metastasis. Methods The expression of HMCBI/MMP9 in 69 specimens of NSCLC and 20 specimens of paraoancerous tissues were determined with the immunohisto-chemical S-P method. The related data of the expression of HMCB1/MMP9 and their clinical and pathological features were statistically analyzed. Results 1. In the NSCLC group ,HMCB1/MMP9 expression positive rate were higher than that in the edge of carcinoma ( con-trol group ). 2. The expression of HMCB1 had a positive correlation with MMP9 in NSCLC invasion and metastasis. Conclusion By testing HMCBI /MMP9 in NSCLC and adjacent tissue, we found that both may play a synergistic role in the process of NSCLC invasion and metastasis. So co-examining HMCBI and MMP9 may be providing basis for diagnosis and prognosis of NSCLC.%目的 探讨HMGB1和MMP9在NSCLC转移过程中的作用.方法 应用免疫组化S-P法检测69例非小细胞肺癌(NSCLC)和20例癌旁组织中HMGB1及MMP9的表达情况,结合临床、病理参数进行统计学分析.结果 1、HMGB1/MMP9二者在NSCLC组织的阳性表达率高于癌旁组织;两组之间差异有统计学意义(P<0.05);2、HMGB1和MMP9在非小细胞肺癌及癌旁组织中表达呈正相关.结论 HMGB1/MMP9联合检测,在NSCLC浸润转移过程中可能起协同作用,可为NSCLC诊断及判断预后提供依据.

  1. 慢性心力衰竭患者血清MMP-9和hs-CRP的表达%Expressions of serum MMP-9 and hs-CRP in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    郑利平

    2012-01-01

    Objective To investigate the changes of serum matrix metalloproteinase-9(MMP-9) and high sensitive Creactive protein(hs-CRP) expressions in the patients with chronic heart failure (CHF). Methods A total of 120 CHF patients was divided into 4 groups according to NYHA cardiac function classes of Ⅰ ,Ⅱ , Ⅲ and Ⅳ. The expression levels of MMP-9 and hs-CRP were detected with ELISA and Latex enhanced immunoturbidimetric assay, respectively, and compared among 4 NYHA cardiac cardiac function classes. Results The expression levels of MMP-9 and hs-CRP were increased as the cardiac function became worsen(P<0. 05). The expression of serum MMP-9 was positively correlated to that of hs-CRP(r=0. 716,P<0. 01). Conclusion When the cardiac dysfunction becomes severe in CHF patients,the expressions of MMP-9 and hs-CRP are remarkably increased, which may participate in the myocardial remodeling of CHF.%目的 探讨基质金属蛋白酶9(MMP-9)和高敏C反应蛋白(hs-CRP)在慢性心力衰竭(CHF)患者的表达.方法 CHF患者120例,ELISA检测血清MMP-9表达,乳胶增强免疫比浊法检测血清hs-CRP水平.比较不同NYHA心功能状态患者MMP-9和hs-CRP的表达差异.结果 随着心功能的恶化,MMP-9和hs-CRP的表达水平显著升高(P<0.05).CHF患者外周血MMP-9和hs-CRP的表达水平呈正相关(r=0.716,P<0.01).结论 CHF患者外周血MMP-9和hs-CRP表达水平随着心功能的减低而升高,MMP-9和hs-CRP表达可能参与了CHF心肌重构的病理过程.

  2. Role of MMP-3 and MMP-9 and their haplotypes in risk of bladder cancer in North Indian cohort.

    Science.gov (United States)

    Srivastava, Priyanka; Mandhani, Anil; Kapoor, Rakesh; Mittal, Rama D

    2010-11-01

    Matrix metalloproteinases (MMPs) play critical roles in cancer development and progression. Nonsynonymous single nucleotide polymorphisms (SNPs) in functional domain of MMP-3 and MMP-9 contribute appreciably to cancer predisposition and aggression. To test this proposition we examined whether six SNPs of the MMP-3 and MMP-9 genes are associated with risk of bladder cancer (BC) in a North Indian population. Six SNPs of MMP-3 and MMP-9 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a case-control study including 200 BC patients and 200 age/gender/ethnicity-matched controls. Increased risk for BC susceptibility was observed in MMP-3 (1171) 5A/5A [P = 0.022; odds ratio (OR), 3.46; 95% confidence interval (CI), 1.20-9.98], MMP-9 (Q279R) QQ (P = 0.048; OR, 1.92; 95%CI, 1.01-3.66), MMP-9 (P574R) PR (P BCG)-treated non-muscle-invasive BC (NMIBC) patients (log-rank P = 0.025). Our data suggested that MMP-3-1171 5A/5A and MMP-9 (Q279R) QQ, MMP-9 (P574R) PR, PR + RR, and R allele are associated with high risk of BC.

  3. Anti-inflammatory activities of inotilone from Phellinus linteus through the inhibition of MMP-9, NF-κB, and MAPK activation in vitro and in vivo.

    Science.gov (United States)

    Huang, Guan-Jhong; Huang, Shyh-Shyun; Deng, Jeng-Shyan

    2012-01-01

    Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells and λ-carrageenan (Carr)-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK) [extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), p38], and nuclear factor-κB (NF-κB), matrix-metalloproteinase (MMP)-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-κB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4(th) and the 5(th) h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5(th) h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-α) levels on serum at the 5(th) h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2), NF-κB, and MMP-9 expressions at the 5(th) h in the edema paw. An intraperitoneal (i.p.) injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-κB, and MMP-9 and increase the

  4. Anti-inflammatory activities of inotilone from Phellinus linteus through the inhibition of MMP-9, NF-κB, and MAPK activation in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Guan-Jhong Huang

    Full Text Available Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS-stimulated mouse macrophage RAW264.7 cells and λ-carrageenan (Carr-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO production, and the inducible nitric oxide synthase (iNOS expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK [extracellular signal-regulated protein kinase (ERK, c-Jun NH(2-terminal kinase (JNK, p38], and nuclear factor-κB (NF-κB, matrix-metalloproteinase (MMP-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-κB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4(th and the 5(th h after Carr administration, and it increased the activities of catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx. We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA level in the edema paw at the 5(th h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-α levels on serum at the 5(th h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2, NF-κB, and MMP-9 expressions at the 5(th h in the edema paw. An intraperitoneal (i.p. injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo. The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-κB, and MMP-9 and increase the activities

  5. Recognition of Streptococcus pneumoniae and muramyl dipeptide by NOD2 results in potent induction of MMP-9, which can be controlled by lipopolysaccharide stimulation.

    Science.gov (United States)

    Vissers, Marloes; Hartman, Yvonne; Groh, Laszlo; de Jong, Dirk J; de Jonge, Marien I; Ferwerda, Gerben

    2014-12-01

    Matrix metallopeptidase 9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in pathogenesis during Streptococcus pneumoniae infection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show here that the Gram-positive bacteria used in this study induced large amounts of MMP-9, in contrast to the Gram-negative bacteria that were used. An important pathogen-associated molecular pattern (PAMP) for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using peripheral blood mononuclear cells (PBMCs) from Crohn's disease patients with nonfunctional NOD2 showed that MMP-9 induction by Streptococcus pneumoniae and MDP is NOD2 dependent. Increasing amounts of lipopolysaccharide (LPS), an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be regulated posttranscriptionally, independently of tissue inhibitor of metalloproteinase 1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show that Streptococcus pneumoniae is able to induce large amounts of MMP-9. These high MMP-9 levels are potentially involved in Streptococcus pneumoniae pathogenesis.

  6. MMP-9 Levels and IMT of Carotid Arteries are Elevated in Obese Children and Adolescents Compared to Non-Obese

    Directory of Open Access Journals (Sweden)

    Claudio Andrade

    Full Text Available Abstract Background: Childhood obesity is associated with increased risk of atherosclerosis and cardiovascular disease in adulthood. Increased intima-media thickness (IMT of the carotid artery is linked to the initiation and progression of the chronic inflammatory processes implicated in cardiovascular disease. Matrix metalloproteinase-9 (MMP-9 plays an important role in the degradation of the extracellular matrix and, consequently, in the development, morphogenesis, repair and remodeling of connective tissues. Objectives: (i to determine and compare the concentrations of MMP-9, tissue inhibitor of metalloproteinase -1 (TIMP-1, and MMP-9/TIMP-1 ratio in obese and non-obese children and adolescents; (ii to investigate the association of these markers with common and internal IMT of carotid arteries. Methods: Cross-sectional study involving 32 obese and 32 non-obese (control individuals between 8 - 18 years of age. Results: Significantly (p < 0.05 higher values of MMP-9 concentration, as well as a higher MMP-9/TIMP-1 ratio were detected in the obese group compared to control counterparts. Common and internal carotid IMT values were significantly higher (p < 0.001 in the obese group compared to the control group. Positive correlations were observed between the common carotid IMT values and MMP-9 concentrations as well as MMP-9/TIMP-1 ratio. Conclusions: Our data demonstrate that obese children and adolescents present higher mean IMT values, plasma MMP-9 and MMP-9/TIMP-1 ratio compared to the non-obese. Thus, these findings indicate that this group presents a risk profile for early atherosclerosis.

  7. MMP-1 and MMP-9 regulate epidermal growth factor-dependent collagen loss in human carotid plaque smooth muscle cells.

    Science.gov (United States)

    Rao, Velidi H; Kansal, Vikash; Stoupa, Samantha; Agrawal, Devendra K

    2014-02-01

    Mechanisms underlying the rupture of atherosclerotic plaque, a crucial factor in the development of myocardial infarction and stroke, are not well defined. Here, we examined the role of epidermal growth factor (EGF)-mediated matrix metalloproteinases (MMP) on the stability of interstitial collagens in vascular smooth muscle cells (VSMCs) isolated from carotid endarterectomy tissues of symptomatic and asymptomatic patients with carotid stenosis. VSMCs isolated from the carotid plaques of both asymptomatic and symptomatic patients were treated with EGF. The MMP-9 activity was quantified by gelatin zymography and the analysis of mRNA transcripts and protein for MMP-9, MMP-1, EGFR and collagen types I, Col I(α1) and collagen type III, Col III(α1) were analyzed by qPCR and immunofluorescence, respectively. The effect of EGF treatment to increase MMP-9 activity and mRNA transcripts for MMP-9, MMP-1, and EGFR and to decrease mRNA transcripts for Col I(α1) and Col III(α1) was threefold to fourfold greater in VSMCs isolated from the carotid plaques of symptomatic than asymptomatic patients. Inhibitors of EGFR (AG1478) and a small molecule inhibitor of MMP-9 decreased the MMP9 expression and upregulated Col I(α1) and Col III(α1) in EGF-treated VSMCs of both groups. Additionally, the magnitude in decreased MMP-9 mRNA and increased Col I(α1) and Col III(α1) due to knockdown of MMP-9 gene with siRNA in EGF-treated VSMCs was significantly greater in the symptomatic group than the asymptomatic group. Thus, a selective blockade of both EGFR and MMP-9 may be a novel strategy and a promising target for stabilizing vulnerable plaques in patients with carotid stenosis.

  8. Relationship of MMP-2 and MMP-9 expression of SGC7901 with IL-8 in vitro%IL-8与胃癌细胞SGC7901MMP-2和MMP-9表达的关系

    Institute of Scientific and Technical Information of China (English)

    林晓; 王娅兰

    2005-01-01

    目的探讨趋化因子白介素-8(IL-8)与胃癌细胞SGC7901细胞胶原酶MMP-2和MMP-9表达的关系.方法体外细胞培养,MTT法及免疫组化方法检测细胞增殖率及MMP-2,MMP-9蛋白表达.结果 IL-8处理组SGC7901细胞MMP-2表达较对照组(无IL-8)比较,具有显著增强(P<0.05),而MMP-9无明显差异.结论 IL-8能促进细胞SGC7901 MMP-2表达,而对MMP-9无明显影响.

  9. Expression of matrix metalloproteinases (MMP-2 、MMP-9) in the pancreatic carcinoma%胰腺癌组织中MMP-2、MMP-9的表达

    Institute of Scientific and Technical Information of China (English)

    吴俊本; 张洁; 成丕光; 王树静; 巩本刚; 徐怀勇

    2012-01-01

    目的 检测胰腺癌组织基质金属蛋白酶( MMP-2,MMP-9)的表达,分析其与临床病理特征的关系.方法 应用免疫组化SP法检测30例胰腺癌及配对癌旁胰腺组织以及11例慢性胰腺炎、6例正常胰腺组织中MMP-2、MMP-9的表达,运用统计软件SPSS 12.0分析其与临床病理特征的相关性.结果 正常胰腺组织均无MMP-2及MMP-9的表达.慢性胰腺炎组织MMP-2、MMP-9的阳性表达率均为18.2% (2/11).胰腺癌组织MMP-2、MMP-9的阳性表达率分别为63.3% (19/30)和56.7% (17/30);配对癌旁组织的阳性表达率分别为23.3% (7/30)和40.0%( 12/30).胰腺癌组织的MMP-2及MMP-9阳性表达率均显著高于配对癌旁组织(P<0.05);胰腺癌组织及癌旁组织中MMP-2及MMP-9的表达均显著高于慢性胰腺炎组织和正常胰腺组织(P值均<0.05).MMP-2、MMP-9的表达与胰腺癌临床分期、肿瘤大小、分化程度及淋巴结转移相关.结论 胰腺癌组织中MMP-2、MMP-9呈高表达,其高表达与肿瘤的恶性程度相关.%Objective To study the expression of matrix metallopro-teinase-2 (MMP-2),matrix metalloproteinase-9 (MMP-9) in the pancreatic carcinomas. Methods MMP-2,MMP-9 expression were detected by immunohistochemistry in surgically resected specimens ( cancer tissues,cancer-adjacent tissues and normal tissues) from 30 PC patients,11 pancreatitis patients and 6 normal patients.the results were analyzed combined with clinical pathologic characteristics.The data was analyzed by Chi-Square test.Results There was no expression of MMP-2,MMP-9 in normal pancreatic tissues.Both of MMP-2 and MMP-9 expressions were 18.2% in chronic pancreatitis titssues.Expression of MMP-2,MMP-9 were higher in cancer tissues than in cancer-adjacent tissues(63.3% vs 23.3%,56.7% vs 40.0%,P <0.05).There were positive correlation between MMP-2,MMP-9 expression and lymph nodal metastasis,tumor sizes,clinical stage and differentiation of tumor(P <0.05).Conclusions

  10. Twist1,MMP-2和MMP-9在结直肠癌组织中的表达及意义%Expression of Twist1, MMP-2 and MMP-9 in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    杨振忠; 吴正升; 法文; 李守新; 吕永芳

    2011-01-01

    目的:研究Twist1、MMP-2和MMP-9蛋白在结直肠癌组织中的表达及其相互关系.方法:建立组织微阵列平台,应用免疫组织化学方法检测92例结直肠癌组织Twist1、MMP-2和MMP-9蛋白的表达情况.结果:结直肠癌中Twist1的表达率为64.1%,MMP-2和MMP-9阳性率分别为66.3%和67.4%;Twist1的表达与肿瘤淋巴结受累和TNM分期均呈正相关(均P<0.05),并且与患者总生存率和无复发生存率呈负相关(P<0.01,P<0.05);MMP-2、MMP-9蛋白表达与肿瘤淋巴结受累均呈显著正相关(均P<0.01),并且MMP-9蛋白表达与肿瘤大小也呈显著正相关(P<0.01);Twist1表达状况与MMP-9的表达呈显著正相关(r=0.205,P<0.05),而与MMP-2表达无显著相关性.结论:结直肠癌Twist1、MMP-2和MMP-9表达状况与肿瘤侵袭转移有密切关系;MMP-9表达可能在一定水平上受到Twist1调控.%AIM: To investigate the clinical significance of the expression of Twist1, MMP-2 and MMP-9 proteins in colorectal cancer.METHODS: The expression of Twist1, MMP-2 and MMP-9 proteins was examined on tissue chips containing 92 colorectal cancer samples by immunohistochemistry.RESULTS: The positive rates of Twist1, MMP-2 and MMP-9 protein expression in colorectal cancer were 64.1%, 66.3% and 67.4%, respectively.High expression of Twist1 was positively correlated with lymph node metastasis and TNM stage (both P < 0.05) but inversely with patient's overall survival and relapse-free survival (P<0.05 and 0.01, respectively).The expression of MMP-2 and MMP-9 was significantly correlated with lymph node metastasis (both P < 0.01).A positive correlation was also found between MMP-9 expression and tumor size (P < 0.01).The expression of Twist1 was positively correlated with that of MMP-9 (P < 0.05), but not with that of MMP-2 (P >0.05).CONCLUSION: The expression of Twist1, MMP-2 and MMP-9 plays an important role in tumor invasion and metastasis in colorectal cancer.The expression of

  11. Expression and significance of oral lichen planus in MMP-2 and MMP-9%口腔扁平苔藓中MMP-2和MMP-9的表达及意义

    Institute of Scientific and Technical Information of China (English)

    浦光瑞; 张虹

    2012-01-01

    [目的]探索MMP -2和MMP -9与口腔扁平苔藓(oral lichen planus,OLP)的发生、发展乃至癌变潜能的关系.[方法]采用免疫组化SP法检测MMP -2和MMP -9在22例OLP、11例正常口腔黏膜组织、22例白斑和22例口腔鳞癌组织表达.[结果]在正常口腔黏膜、扁平苔藓、白斑和鳞癌组织中MMP -2和MMP -9的表达依次增加.MMP -2和MMP -9在口腔扁平苔藓和白斑中的表达显著高于正常口腔黏膜(P<0.05),但在口腔扁平苔藓和白斑间的表达差异无显著性意义(P>0.05);在鳞癌中的表达显著高于其他3组(P<0.05).[结论] MMP -2和MMP -9表达与OLP的发生、发展乃至癌变潜能有关.%To Explore the relationshiops of MMP -2 and MMP -9 to the OLP occurrence, the development and even the canceration potential. [Methods] Immunohisto ?chemistry was performed to examine expressions of MMP -2 and MMP -9 in 22 OLP, 11 normal oral mucosa, 22 oral leukoplakia and 22 squamous cell carcinoma. [Results] The expression of MMP -2 and MMP -9 increased in turn from normal oral mucosa to OLP, oral leukoplakia and oral squamous cell carcinoma tissues. The expression of MMP -2 and MMP -9 in OLP and oral leukoplakia was significantly higher than that in normal oral mucosa ( P 0. 05) ; The expression of MMP - 2 and MMP - 9 in squamous cell carcinoma was significantly higher than The other three groups (P < 0. 05 ) , there was significant difference. [ Conclusion ] The expression levels of MMP - 2 and MMP - 9 correlate with the occurrence of oral lichen planus, development and e-ven cancer potential, which may be useful indicator to judge the possibility of malignant change of OLP.

  12. VEGF、MMP-2与MMP-9在卵巢癌组织中的表达及其临床意义%Expression and clinical significance of VEGF,MMP-2 and MMP-9 in ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    曾晓林; 彭耀金

    2010-01-01

    目的:探讨VEGF、MMP-2和MMP-9在卵巢癌组织中的表达及其与卵巢癌发生发展的关系.方法:采用免疫组织化学法检测VEGF、MMP-2和MMP-9在正常卵巢组织、卵巢癌组织中的表达,并对三者的相关性进行分析.结果:卵巢癌组织中VEGF、MMP-2和MMP-9蛋白的表达阳性率显著高于正常卵巢组织(P<0.05),且在卵巢癌Ⅲ~Ⅳ期患者标本中阳性率高于Ⅰ~Ⅱ期(P<0.05);VEGF、MMP-2和MMP-9蛋白阳性表达率与卵巢癌临床分期和淋巴结转移有关(P<0.05).结论:正常卵巢组织和卵巢癌组织中VEGF、MMP-2和MMP-9蛋白含量的变化一致;VEGF、MMP-2和MMP-9均参与了卵巢癌的发生发展过程,三者间可能有协同作用.

  13. Urinary neutrophil-gelatinase associated lipocalin is a more prognostic biomarker to distinguish antenatal hydronephrosis in neonates

    Directory of Open Access Journals (Sweden)

    Hamid MohammadJafari

    2013-09-01

    Results: There was a significant difference in uNGAL concentration between AH patients and controls (0.80 ± 0.26 and 0.29 ± 0.27 ng/ml, p<0.0001. However, the levels of uNGAL was not significantly deviated between AH patients with VUR compared to those without VUR (0.84 ± 0.34 vs. 0.75 ± 0.13, p=0.419. Standardization of NGAL based on urinary creatinine (uNGAL/uCr showed a significantly difference between AH neonates with VUR compared to those without VUR (2.43±1.61 vs. 1.91±0.79, p<0.0001. Receiver operator characteristic (ROC analysis revealed higher prognostic power of uNGAL for identifying AH with a sensitivity 95.7%, and specificity 84.2%. Meanwhile, the levels of uNGAL or NGAL/uCr ratio did not correlate with reflux grade or laterality. Conclusion: The urinary level of NGAL and NGAL/uCr ratio might be a surrogate non invasive, reliable tool to distinguish hydronephrosis.

  14. Neutrophil gelatinase-associated lipocalin (NGAL/Lcn2) is upregulated in gastric mucosa infected with Helicobacter pylori

    DEFF Research Database (Denmark)

    Alpízar-Alpízar, Warner; Laerum, Ole Didrik; Illemann, Martin

    2009-01-01

    characterized here the pattern of expression of NGAL/Lcn2 in gastric mucosa (45 non-neoplastic and 38 neoplastic tissue samples) and explored the connection between NGAL/Lcn2 expression and H. pylori infection. Immunohistochemical analysis showed high NGAL/Lcn2 expression in normal and gastritis-affected mucosa...... compared to low expression in intestinal metaplasia, dysplasia, and gastric cancer. In normal and gastritis-affected mucosa (n=36 tissue samples), NGAL/Lcn2 was more frequently seen in epithelial cells located at the neck and base of the glands in H. pylori-positive cases than in similar epithelial cells...... of noninfected cases (Fisher's exact test, p=0.04). In conclusion, the high expression of NGAL/Lcn2 in normal and gastritis-affected mucosa infected with H. pylori suggests that NGAL/Lcn2 is upregulated locally in response to this bacterial infection. It is discussed whether this may have a causal relation...

  15. Sex-specific associations between Neutrophil Gelatinase-Associated Lipocalin (NGAL) and cognitive domains in late-life depression

    NARCIS (Netherlands)

    Naude, P.J.; Boer, J.A. den; Comijs, H.C.; Bosker, F.J.; Zuidersma, M.; Groenewold, N.A.; Deyn, P.P. de; Luiten, P.G.M.; Eisel, U.L.; Oude Voshaar, R.C.

    2014-01-01

    BACKGROUND: Although it is well established that late-life depression is associated with both systemic low-graded inflammation and cognitive impairment, the relation between inflammation and cognition in depressed older persons is still equivocal. The objective of this study is to examine the associ

  16. Serum and Plasma Neutrophil Gelatinase Associated Lipocalin (NGAL) Levels are Not Equivalent in Patients Admitted to Intensive Care

    DEFF Research Database (Denmark)

    Itenov, Theis Skovsgaard; Bangert, Kristian; Christensen, Per Hjort

    2014-01-01

    and EDTA plasma NGAL concentrations in patients admitted to intensive care units (ICUs) and whether these determinations are directly comparable in this setting. METHODS: NGAL was measured in 40 paired samples of serum and EDTA plasma from 25 patients admitted to intensive care with a commercial particle.......8-106). CONCLUSION: NGAL concentration values measured in serum and EDTA plasma cannot be directly compared and should not be used as equivalents in studies of patients admitted to intensive care....... and EDTA plasma values were correlated (Spearman's r = 0.95, P unity (95% confidence interval (CI) 1.0-1.1) and a highly significant intercept of 67.9 ng/ml with a wide confidence interval (95% CI 29...

  17. Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan S; Hoffmann, Søren;

    2016-01-01

    cohorts. RESULTS: Estimated glomerular filtration rate (eGFR) was associated significantly more strongly with plasma NGAL when eGFR was abnormal compared to normal eGFR: a decrease in eGFR of 10 ml/min was associated with an increase in NGAL of 27% (18-36%) versus 4% (1-7%), respectively (p ....001). Leukocyte count and C-reactive protein were the main determinants of plasma NGAL in patients with normal eGFR, whereas eGFR was the main determinant at reduced kidney function. CONCLUSIONS: eGFR determines the association of NGAL with either inflammation or kidney function; in patients with normal eGFR......, plasma NGAL reflects inflammation but when eGFR is reduced, plasma NGAL reflects kidney function, highlighting the dual perception of plasma NGAL. From a clinical perspective, eGFR may be used to guide the interpretation of elevated NGAL levels in patients with STEMI....

  18. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy

    OpenAIRE

    Patel ML; Sachan R; Gangwar R; Sachan P; Natu SM

    2013-01-01

    ML Patel,1 Rekha Sachan,2 Radheyshyam Gangwar,3 Pushpalata Sachan,4 SM Natu51Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India; 2Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh, India; 3Department of Critical Care, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; 4Department of Physiology, King George's Medical University, Lucknow, Uttar Pra...

  19. Comparison of circulating MMP-9, TIMP-1 and CA19-9 in the detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Brünner, Nils; De Muckadell, Ove B Schaffalitzky

    2010-01-01

    Background/Aim: The performance of the circulating tumor markers carbohydrate antigen 19-9 (CA19-9), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were evaluated separately and in combination for their potential value in detecting pancreatic ductal...... adenocarcinoma. PATIENTS AND METHODS: The patients had symptoms of pancreatic cancer. The discriminative strength of MMP-9 and TIMP-1 were compared to that of CA19-9 using receiver operating characteristics curves, area under the curves (AUC), specificity and sensitivity. RESULTS: The sensitivities of MMP-9......, TIMP-1 and CA19-9 in detecting pancreatic ductal adenocarcinoma were 58.82%, 47.1% and 86%, respectively, with specificities of 34.6%, 69.2% and 73%. The AUCs of MMP-9, TIMP-1 and CA19-9 were 0.50, 0.64 and 0.84, respectively. Combining the three markers did not significantly improve detection...

  20. MMP-9和MMP-2基因多态性与原发性肝癌侵袭转移的关系%Correlation of MMP-9 and MMP-2 Gene SNPs with Hepatocellular Carcinoma Invasion and Metastasis

    Institute of Scientific and Technical Information of China (English)

    吴时胜; 邵立华; 李尚日; 张飞; 谢鸿; 张春秀; 刘桂平

    2012-01-01

    Objectlve To investigate the association between MMP-9 and MMP-2 gene SNPs of promoter regions and both infiltration and metastasis in hepatocellular carcinoma. Methods PCR- restriction fragment length polymorphism(PCR-RFLP) technique was applied to detect MMP-2 and MMP-9 promoter SNPs in 28 patients with hepatocellular carcinoma(8 cases with metastasis) and 42 healthy people. Results The risk of early metastasisof MMP-9-1562TT genotype was increased up to 1. 25-fold(95%CI,3. 64 ~ 5. 69),compared with MMP-9-1562CC or CT genotype,and irrelevant to the age or gender of patients. The risk of liver cancer in population harboring MMP-9-1562TT and MMP-2-1306CC or CT genotypes was significantly higher than in those harboring MMP-9-1562TT,MMP-2-t306CC or TT alone. Conclusion MMP-2-1306T/C polymorphism alone is not a risk factor of primary liver cancer,although has syn-ergistic interactions with MMP-9-1562C/T genotype, MMP-2 and MMP-9 gene polymorphism are related to the infiltration and metastasis of primary liver cancer.%目的 探讨原发性肝癌中MMP-9和MMP-2基因多态性表达与原发性肝癌侵袭转移的关系.方法 用聚合酶链反应—限制性片断长度多态性技术,检测MMP-2和MMP-9启动子基因型在28例原发性肝癌患者(其中8例有转移)和42例健康者中的频率.结果 与携带MMP-9- 1562CC和CT基因型相比,携带MMP-9- 1562TT基因型者早期发生侵袭转移的风险增加1.25倍(95%CI:3.64~5.69),且这种风险增高与研究对象的年龄和性别无关,同时携带MMP-9- 1562TT和MMP-2 - 1306CC或CT基因型的个体,惠肝癌的风险性较单一携带的个体显著增高(P<0.5).结论 MMP-2-1306T/C多态性单独与原发性肝癌风险无关,但与MMP-9- 1562C/T多态性可能有基因-基因交互作用.MMP-2和MMP-9基因多态性与原发性肝癌侵袭转移可能相关.

  1. Expression of GPC3, MMP-9 and MMP-14 in Hepatocellular Carcinoma and Their Influence on the Prognosis of Patients

    Directory of Open Access Journals (Sweden)

    Lei CAI

    2016-03-01

    Full Text Available Objective: To explore the expression of glypican-3 (GPC3, metal matrix proteinase (MMP-9 Methods: Totally 112 paraffin-embedded tissue samples of HCC patients were selected as observation group and 70 normal tissue samples were as control group. The expressions of GPC3, MMP-9 and MMP-14 of two groups were detected using immunohistochemistry assay. The positive rates of two groups were calculated. The relationship between the expression of GPC3, MMP-9 and MMP-14 and clinicopathological features, and their influence on the survival time of HCC patients were compared. Results: The positive expression rates of GPC3, MMP-9 and MMP-14 were higher in observation group that those in control group, the differences were statistically significant (P=0.000; P=0.000; P=0.000. The expression of GPC3 had close relationship with tumor volume, differentiated degree, lymphatic metastasis, and PCNA expression. The expression of MMP-9 had close relationship with tumor volume, lymphatic metastasis, and vascular invasion. The expression of GPC3 had close relationship with tumor volume, differentiated degree, lymphatic metastasis, vascular invasion, and proliferating cell nuclear antigen (PCNA expression.Conclusion: GPC3, MMP-9 and MMP-14 are highly expressed in HCC patients, which shows poor prognosis. Therefore, the detection of GPC3, MMP-9 and MMP-14 after surgery has a certain value on assessment of the prognosis of HCC patients.and MMP-14 in hepatocellular carcinoma (HCC, and their influence on the prognosis of HCC patients. There were positive correlations between GPC3 and MMP-9 (r=0.538, P=0.042, MMP-9 and MMP-14 (r=0.430, P=0.024, and GPC3 and MMP-14Kaplan-Meier method showed that the expressions of GPC3, MMP-9 and MMP-14 were associated with the prognosis of HCC patients, and patients with high expressions of GPC3, MMP-9 and MMP-14 had poor prognosis. (r=0.563, P=0.563.

  2. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

    Energy Technology Data Exchange (ETDEWEB)

    Lacorte, Livia M.; Rinaldi, Jaqueline C.; Justulin, Luis A.; Delella, Flávia K. [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil); Moroz, Andrei [Univ Estadual Paulista – UNESP, School of Pharmaceutical Sciences, Department of Bioprocess and Biotechnology, Cell Culture Laboratory, Araraquara, SP (Brazil); Felisbino, Sérgio L., E-mail: felisbin@ibb.unesp.br [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil)

    2015-02-20

    Matrix metalloproteinases (MMPs) are zinc (Zn{sup 2+}) and calcium (Ca{sup 2+}) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd{sup 2+}) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd{sup 2+} intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl{sub 2} diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl{sub 2}) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl{sub 2} intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd{sup 2+} treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl{sub 2}, respectively, even in the presence of 10 mM of CaCl{sub 2} within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its

  3. Expression of MMP-9 in hepatic sinusoidal obstruction syndrome induced by Gynura segetum

    Institute of Scientific and Technical Information of China (English)

    Xia-zhen YU; Tao JI; Xue-li BAI; Liang LIANG; Lin-yan WANG; Wei CHEN; Ting-bo LIANG

    2013-01-01

    Background and objective:Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by painful hepatomegaly,ascites,increased body weight,and jaundice.Gynura segetum (Compositae),a plant widely used in Chinese traditional medicine,often leads to the development of HSOS.However,the mechanism is unclear.The aim was to study the role of matrix metalloproteinase-9 (MMP-9) in the onset of HSOS induced by Gynura segetum.Methods:Twenty-five male Sprague-Dawley rats were randomly divided into two groups.Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks; five control rats were exposed to tap water alone.Liver sections were evaluated by light microscopy with a modified scoring system.Routine transmission electron microscopy (TEM) methods were used to evaluate the ultrastructual features of fixed liver tissue,and blood samples were collected to determine liver enzyme concentrations.MMP-9 expression was assessed by both immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) methods.Results:A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract.The treated rats presented clinical symptoms and the histopathological manifestation of HSOS,including abnormal liver enzyme concentrations (alanine aminotransferase (ALT):(84.8±13.62) vs.(167.0±72.63) U/L,P<0.05; aspartate aminotransferase (AST):(27.6±6.31)vs.(232.8±108.58) U/L,P<0.05).Hematoxylin and eosin (H&E) staining and TEM together revealed deposition of red blood cells,the damage and destruction of hepatic sinusoidal endothelial cells,collapse of hepatic sinusoids,hemorrhage of subendothelial cells,atrophy and destruction of hepatocytes,etc.Compared with controls,the expression of MMP-9 in the blood sample,the lung and liver tissues of HSOS rats was increased.Conclusions:MMP-9 may have an important role in early pathological changes of HSOS,and thus the onset of the disease.

  4. Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress

    Directory of Open Access Journals (Sweden)

    Arun MZ

    2016-04-01

    Full Text Available Mehmet Zuhuri Arun,1 Buket Reel,1 Graciela B Sala-Newby,2 Mark Bond,2 Aikaterini Tsaousi,2 Perry Maskell,2 Andrew C Newby21Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 2Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, UK Background: Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression.Methods: Rat VSMCs were stimulated by PDGF (50 ng/mL plus TNF-α (10 ng/mL or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 µM or with apocynin (20 nM for 2 hours, then zoledronate (100 µM was added into 2% fetal calf serum containing medium for 24 hours.Results and discussion: Using isolated rat VSMCs in culture, zoledronate (100 µM increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-κB pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-κB activation and MMP-9 and MMP-13 up-regulation by

  5. Role Of MMP-2 and MMP-9 in Resistance to Drug Therapy in Patients with Resistant Hypertension

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    Leandro Lacerda

    2015-01-01

    Full Text Available Background: Despite the increased evidence of the important role of matrix metalloproteinases (MMP-9 and MMP‑2 in the pathophysiology of hypertension, the profile of these molecules in resistant hypertension (RHTN remains unknown. Objectives: To compare the plasma levels of MMP-9 and MMP-2 and of their tissue inhibitors (TIMP-1 and TIMP-2, respectively, as well as their MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios, between patients with controlled RHTN (CRHTN, n=41 and uncontrolled RHTN (UCRHTN, n=35. In addition, the association of those parameters with clinical characteristics, office blood pressure (BP and arterial stiffness (determined by pulse wave velocity was evaluate in those subgroups. Methods: This study included 76 individuals diagnosed with RHTN and submitted to physical examination, electrocardiogram, and laboratory tests to assess biochemical parameters. Results: Similar values of MMP-9, MMP-2, TIMP-1, TIMP-2, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios were found in the UCRHTN and CRHTN subgroups (P>0.05. A significant correlation was found between diastolic BP (DBP and MMP-9/TIMP-1 ratio (r=0.37; P=0.02 and DPB and MMP-2 (r=-0.40; P=0.02 in the UCRHTN subgroup. On the other hand, no correlation was observed in the CRHTN subgroup. Logistic regression models demonstrated that MMP-9, MMP-2, TIMP-1, TIMP-2 and their ratios were not associated with the lack of BP control. Conclusion: These findings suggest that neither MMP-2 nor MMP-9 affect BP control in RHTN subjects.

  6. MMP-9 and pulmonary fibrosis%基质金属蛋白酶-9与肺纤维化

    Institute of Scientific and Technical Information of China (English)

    卞秀娟; 郑金旭

    2006-01-01

    基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)是一种金属离子依赖的蛋白酶,通过多种途径参与特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的发病机制,本文就MMP-9的基本特性及其与肺纤维化的关系进行综述.

  7. Group IVA phospholipase A2-associated production of MMP-9 in macrophages and formation of atherosclerotic lesions.

    Science.gov (United States)

    Ii, Hiromi; Hontani, Naoya; Toshida, Issei; Oka, Mayuko; Sato, Takashi; Akiba, Satoshi

    2008-03-01

    Matrix metalloproteinase-9 (MMP-9) is involved in atherogenesis, and the production of MMP-9 in macrophages is considered to be mediated by the arachidonic acid cascade. The present study examined the possible involvement of group IVA phospholipase A2 (IVA-PLA2), a key enzyme in the arachidonic acid cascade, in the production of MMP-9 induced by oxidized low-density lipoprotein (oxLDL) in macrophages and high-fat diet-induced formation of atherosclerotic lesions using IVA-PLA2-deficient mice (C57BL/6 background). In wild-type mouse peritoneal macrophages, oxLDL induced an increase in MMP-9 in the culture medium. The oxLDL-promoted production of MMP-9 was markedly reduced in IVA-PLA2-deficient macrophages compared to wild-type macrophages. Feeding of wild-type mice with a high-fat diet caused the formation of early atherosclerotic lesions in the aortic root with increases in MMP-9 and macrophages in the lesions and with higher serum levels of total cholesterol. Such lesions were apparently less severe in IVA-PLA2-deficient mice fed a high-fat diet, despite higher total cholesterol levels. Under the conditions, a high-fat diet reduced the serum levels of high-density lipoprotein-cholesterol (HDL-C) in wild-type mice. However, IVA-PLA2-deficient mice fed a high-fat diet were protected against the decrease in HDL-C levels. The present results suggest that IVA-PLA2 is involved in the oxLDL-induced production of MMP-9 in macrophages and the high-fat diet-induced formation of early atherosclerotic lesions. The protection against the lesions in IVA-PLA2-deficient mice may be ascribable, in part, to the impaired production of MMP-9 and/or the maintained levels of HDL-C.

  8. Analysis of the Relationship between Expressions of TF and MMP-9 and Prognosis of Breast Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    Jianxin Zhao; Zengmao Lin; Hongwei Yao; Yuanlian Wan

    2008-01-01

    OBJECTIVE To investigate expression of the tissue factor(TF) and matrix metalloproteinase-9 (MMP-9) in breast cancers,and to assess their expression in relation to possible prognostic significance.METHODS The expression of TF and MMP-9 in 71 breast cancer specimens were determined by EnVision immunohistochemistry,and the positive expressions related to the patient clinical outcome.RESULTS Positive rates of TF and MMP-9 staining were respectively 43.7% and 42.3%. K-M monofactorial analysis showed that the 5-year survival rate of the patients with a positive expression of TF and MMP-9 was lower than those with negative expression (P < 0.05). However, the COX multifactorial analysis indicated that TNM staging and lymph node metastasis were the prognostic factors for breast cancer patients, and that TF and MMP-9 could not be used as the independent prognostic factors (P> 0.05).CONCLUSION The positive rates of TF and MMP-9 were considerably high in breast cancers, which could provide useful information for patient prognosis.

  9. Crosstalk between obesity and MMP-9 in cardiac remodelling -a cross-sectional study in apparent treatment-resistant hypertension.

    Science.gov (United States)

    Ritter, Alessandra Mileni Versuti; de Faria, Ana Paula; Barbaro, Natália; Sabbatini, Andréa Rodrigues; Corrêa, Nathália Batista; Brunelli, Veridiana; Amorim, Rivadavio; Modolo, Rodrigo; Moreno, Heitor

    2017-04-01

    The balance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) plays a key role in the development of hypertension and obesity. We aimed to evaluate the levels of MMP-2 and 9 and TIMP-2 and -1 in obese and non-obese apparent treatment-resistant hypertensive subjects (aTRH) and its association with cardiac hypertrophy. This cross-sectional study enrolled 122 subjects and divided into obese aTRH (n = 67) and non-obese (n = 55) group. Clinical and biochemical data were compared between both groups, including office BP, ambulatory BP, plasma MMP-2 and 9, TIMP-2 and 1 and left ventricular mass index (LVMI). We found higher MMP-9 levels and MMP-9/TIMP-1 ratio in obese aTRH subjects but no difference in MMP-2 and TIMP-1 levels. Obesity influenced MMP-9 levels [β = 20.8 SE =8.6, p = 0.02) independently of potential confounders. In addition, we found a positive correlation between MMP-9 and anthropomorphic parameters. Finally, obese aTRH subjects with left ventricular hypertrophy (LVH) had greater MMP-9 levels compared with non-obese with LVH. Our study suggests that MMP-9 levels are influenced by obesity and may directly participate in the progressive LV remodelling process, suggesting a possible role for a higher cardiovascular risk in apparent resistant hypertensive subjects.

  10. EXPRESSION AND CLINICAL SIGNIFICANCE OF HMGB1 AND MMP-9 IN ENDOMETRIAL CARCINOMA%HMGB1、MMP9在子宫内膜癌中的表达和临床意义

    Institute of Scientific and Technical Information of China (English)

    段玉真; 周晓慧; 张玉娟

    2016-01-01

    目的::探讨高迁移率组蛋白1(HMGB1)和基质金属蛋白酶-9(MMP-9)mRNA在子宫内膜癌中的表达水平和临床意义。方法:应用RT-PCR法检测正常子宫、单纯性增生症、非典型增生症和子宫内膜癌子宫内膜组织HMGB1和MMP9 mRNA的表达水平。结果:子宫内膜癌组织HMGB1、MMP-9 mRNA的表达量明显高于正常子宫、单纯性增生症、非典型增生症子宫内膜组织(P<0.05);子宫内膜癌组织HMGB1、MMP-9 mRNA的表达均与FIGO分期、淋巴结转移和浸润深度有关(P<0.05)。结论:HMGB1、MMP-9在子宫内膜癌的发生、发展和转移过程中可能起着重要作用。%[ABSTRACT]Objective:To investigate the expression and clinical signiifcance of high-mobility group box 1 protein (HMGB1) and matrix metalloproteinases-9 (MMP-9) mRNA in endometrial carcinoma. Methods:RT-PCR was used to detect the HMGB1 and MMP-9 mRNA expression level in normal endometrial tissue, endometrial hyperplasia, atypical endometrial hyperplasia and endometrial carcinoma. Results:The HMGB1 and MMP-9 mRNA expression level in endometrial carcinoma were obviously higher than normal endometrial tissue, endometrial hyperplasia and atypical endometrial hyperplasia (P<0.05). In endometrial carcinoma, the expression of HMGB1 and MMP-9 were all related to FIGO stage, lymph node metastasis and inifltration depth (P<0.05). Conclusions:HMGB1 and MMP-9 may play important role in genesis, development and metastasis of endometrial carcinoma.

  11. CCR7上调MMP-9表达促进非小细胞肺癌转移%Chemokine Receptor 7 Induces Metastasis of NSCLC via Upregulating MMP-9 Expression

    Institute of Scientific and Technical Information of China (English)

    李洋; 刘巍; 方莉; 南娟; 张占雀; 周清华

    2010-01-01

    背景与目的 趋化因子激素受体(CC chemokine receptor 7,CCR7)与非小细胞肺癌(non-small celllung cancer,NSCLC)的淋巴结转移密切相关,但CCR7促进其淋巴结转移的机制尚不明了.本研究通过观察CCR7和MMP.9在NSCLC组织中的表达和相互关系.探讨CCR7促进NSCLC淋巴结转移的机制.方法 应用免疫组织化学染色(SP法)检测90例NSCLC组织中CCR7、MMP-9的表达;将BEI细胞经趋化因子CCLl9处理24 hA,应用RT-PCR和Western blot方法检测MMP-9 mRNA和蛋白表达水平.结果 免疫组织化学结果显示:CCR7主要表达于癌细胞胞质和(或)胞膜,MMP-9主要表达于癌细胞胞质,NSCLC中CCR7、MMP.9阳性表达率分别为70%(63/90)和65.5%(59/90),X2检验显示CCR7和MMP-9表达与NSCLC的临床病理分期(P=0.003,P=0.001)和淋巴结转移(P=0.0042 P=0.003)密切相关,而与年龄、组织学类型、分化程度无关(P>0.05).此外,CCR7和MMP-9表达正相关(r=0.342,P=0.001).CCL21处理组BEI细胞后MMP-9 mRNA和蛋白水平均上调(P<0.05).结论 CCR7和MMP-9表达与NSCLC侵袭转移密切相关,CCL19/CCR7通过上调NSCLC中MMP-9表达促进其转移.

  12. MMP-9、TIMP-1和VEGF在牙龈癌中的表达及意义%Expressions of MMP-9, TIMP-1 and VEGF in Gingival Carcinoma and Their Significance

    Institute of Scientific and Technical Information of China (English)

    李芳凝; 李金源

    2011-01-01

    [Objective]To explore the expressions of matrix mcta11oprotcin-9(MMP-9) , tissue inhibitor of mctalloprotcinasc-1 (TIMP-1) and vascular cndothclial growth factor(VKGF) in gingival carcinoma and their correlation. [Mcthods]Thc expression of MMP-9, TIMP-1 and VEGF in 66 gingival carcinoma tissues and 16 normal gum tissues were detected by SP immunohistochemistry method. The correlation of the expressions with clinical pathology and prognosis was analyzed. [Results] There was significant difference in the positive expression of MMP-9 and VEGF among the well-differentiated, moderately-differentiated and poorly-differen tiated gingival carcinomaC P 0. 05). [Conclusion]MMP-9, TIMP-1 and VEGF may be involved in the pathogencsis and development of gingival carcinoma through the pathway of angiogencsis. The combination detection of MMP-9, TIMP-1 and VEGF may be helpful for the diagnosis, treatment and prognostic assessment of gingival carcinoma.%[目的]探讨基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1)及血管内皮生长因子(VEGF)在牙龈癌组织中的表达及相关性.[方法]采用免疫组化SP法检测66例牙龈癌和16例正常牙龈组织中MMP-9,TIMP-1和VEGF的表达情况,分析其表达的相关性.[结果]在高分化、中分化及低分化牙龈癌中MMP-9和VEGF的阳性表达差异均有显著性(P0.05),MMP-9与TIMP-1在牙龈癌中的表达存在负相关(P0.05).[结论]MMP-9,TIMP-1和VEGF三者可能通过"血管生成"通路参与了牙龈癌的发生和发展过程,联合检测三项指标的表达状况可能有助于牙龈癌的诊断、治疗和评估预后.

  13. 前列腺癌中MMP-9和VEGF的表达及相关性研究%An Association Study of MMP-9 and VEGF Protein EXpression in Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    牛军

    2014-01-01

    目的:探讨基质金属蛋白酶( MMP-9)和血管内皮生长因子( VEGF)在前列腺癌组织中的表达以及两者的关系。方法:应用免疫组织化学技术检测120例前列腺增生( BPH)和120例前列腺癌( PCa)组织中MMP-9和VEG的表达水平,并分析两者表达与前列腺癌临床病理特征的关系。结果:120例PCa中MMP-9和VEGF阳性表达率分别为85.01%、83.32%,与BPH组织进行比较,差异均有统计学意义( P <0.05)。MMP-9和VEGF与PCa的病理分级和临床分期有关,且二者呈正相关。结论:MMP-9和VEGF蛋白在PCa中高表达,两者与前列腺癌的发生、发展相关,可以作为预后的判断指标。%ObjectiVe:To eXplore the eXpression of matriX metallo proteinases -9( MMP -9 )and Vascular endothelial growth factor( VEGF)in prostatic cancer( PCA)and the relations between them. Methods:The eXpression of VEGF and MMP-9 in 120 cases of prostate cancer and 120 case s of BPH were detected by immunohistochemistry,with the relationship of their eXpression with clinical characteristics of prostatic cancer further analyzed. ResuIts:The positiVe rate of MMP-9 and VEGF eX-pression in 120 cases PCA is 85. 01 % and 83. 32 %,respectiVely,significantly different from that in BPH( P <0. 0 5). The eXpression of MMP-9 and VEGF in prostate cancer was positiVely correlated with pathological grading and clinical staging of PCA. ConcIusion:The oVer eXpression of MMP-9 and VEGF in PCA is correlated to the generation and the deVelopment of the prostatic carcinoma,which can be taken as an indeX of the prognosis of PCA.

  14. The expression and significance of NF-κB and MMP-9 in cervical carcinoma%NF-κB、MMP-9在宫颈癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    赵玉婵; 李莲; 张连梅; 刘晓兰

    2013-01-01

    Objective To investigate the expression and clinical significance of nuclear factor kappa -B ( NF-κB ) and matrix metalloproteinase ( MMP-9 ) in cervical carcinoma .Methods The expression levels of NF-κB and MMP-9 were detected by immunohistochemistry in 80 cases of cervical carcinoma (CSES),70 cases of cervical intraepithelial neoplasm (CIN) and 50 cases of normal cervical tissues (NCE).The correlation between their expression levels and clinical pathological characteristics was analyzed .Results The expression levels of NF-κB and MMP-9 in CSES were significantly higher than those in CIN and NCE ( P <0.05).The expression levels of NF-κB and MMP-9 were correlated to the pathological classification , clinical staging and lymph node metastasis of cervical carcinoma ( P <0.05),however,which were not related to patient ’ s age and histological types,moreover the expression of NF-κB was positively related with that of MMP-9 ( P <0.05).Conclusion The overexpression of NF-κB and MMP-9 exists in patients with cervical carcinoma ,which may play an important role in the pathogenesis ,development ,invasion and metastasis of cervical carcinoma and NF-κB and MMP-9 can be used as the indexes of diagnosis and prognosis evaluation for cervical carcinoma .%目的观察核转录因子-κB (nuclear factor kappa-B,NF-κB)和MMP-9(matrix metalloprotein-ase,MMP-9)在宫颈癌组织中的表达及临床意义。方法采用免疫组织化学 SP 法检测80例宫颈癌(CSES)、70例子宫颈上皮内瘤样变(CIN)及50例正常子宫颈组织(NCE)NF-κB和MMP-9蛋白表达水平,分析其与临床病理特征的关系。结果在CSES、CIN及NCE中, NF-κB蛋白阳性表达率分别为72.5%、18.6%、0%,MMP-9蛋白阳性表达率分别为68.8%、15.7%、0;即CSES中NF-κB和MMP-9蛋白表达显著高于CIN和NCE,差异具有统计学意义( P <0.05)。 NF-κB、MMP-9表达与宫颈癌不同的病理分级、临床分期

  15. Porphyromonas gingivalis decreases osteoblast proliferation through IL-6-RANKL/OPG and MMP-9/TIMPs pathways

    Directory of Open Access Journals (Sweden)

    Le Xuan

    2009-01-01

    Full Text Available Background: Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption. This bacterium exerts its pathogenic effect indirectly through multiple virulence factors, such as lipopolysaccharides, fimbriae, and proteases. Another possible pathogenic path may be through a direct interaction with the host′s soft and hard tissues (e.g., alveolar bone, which could lead to periodontitis. Aims and Objectives: The aim of the present study was to investigate the direct effect of live and heat-inactivated P gingivalis on bone resorption, using an in vitro osteoblast culture model. Results: Optical microscopy and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide MTT assay revealed that live P gingivalis induced osteoblast detachment and reduced their proliferation. This effect was specific to live bacteria and was dependent on their concentration. Live P gingivalis increased IL-6 mRNA expression and protein production and downregulated RANKL and OPG mRNA expression. The effect of live P gingivalis on bone resorption was strengthened by an increase in MMP-9 expression and its activity. This increase was accompanied by an increase in TIMP-1 and TIMP-2 mRNA expression and protein production by osteoblasts infected with live P gingivalis. Conclusion: Overall, the results suggest that direct contact of P gingivalis with osteoblasts induces bone resorption through an inflammatory pathway that involves IL-6, RANKL/OPG, and MMP-9/TIMPs.

  16. Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion

    Directory of Open Access Journals (Sweden)

    Elene Sapharikas

    2015-06-01

    Full Text Available Critical limb ischemia (CLI induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate. Monocytes negatively isolated with magnetic beads from peripheral blood of healthy donors were treated with fucoidan. Fucoidan induced a 1.5-fold increase in monocyte adhesion to gelatin (p < 0.05 and a five-fold increase in chemotaxis in Boyden chambers (p < 0.05. Fucoidan also enhanced migration 2.5-fold in a transmigration assay (p < 0.05. MMP9 activity in monocyte supernatants was significantly enhanced by fucoidan (p < 0.05. Finally, Western blot analysis of fucoidan-treated monocytes showed upregulation of ERK/p38 phosphorylation. Inhibition of ERK/p38 phosphorylation abrogated fucoidan enhancement of migration (p < 0.01. Fucoidan displays striking biological effects, notably promoting monocyte adhesion and migration. These effects involve the ERK and p38 pathways, and increased MMP9 activity. Fucoidan could improve critical limb ischemia by promoting monocyte recruitment.

  17. Prognostic values of ETS-1, MMP-2 and MMP-9 expression and co-expression in breast cancer patients.

    Science.gov (United States)

    Puzovic, V; Brcic, I; Ranogajec, I; Jakic-Razumovic, J

    2014-01-01

    The aim of this study was to analyse expression of ETS-1 protein and two gelatinases (MMP-2 and MMP-9) and their possible prognostic value in breast carcinoma patients, as well as correlation of their expression with other known prognostic factors such as tumor size, grade, vascular invasion, steroid receptor values, HER2 values and proliferative index. The expression of MMP-2, MMP-9 and ETS-1 was immunohistochemicaly analysed in 121 consecutive primary breast carcinoma patients who underwent surgery at the Clinical Hospital Centre Zagreb during 2002. Three representative areas from each tumor paraffin blocks were taken and arranged on a recipient paraffin block with predefined coordinates for simultaneous analyses of multiple tissue samples (TMA). ETS-1, MMP-2 and MMP-9 expression and co-expression were correlated with other clinico-pathological parameters and based on the available clinical follow up data survival analysis was performed. The ETS-1 protein is found to be expressed in tumor cell nuclei and cytoplasm as well as in stromal lymphocytes, fibroblasts and endothelial cells. MMP-2 and MMP-9 were found to be expressed in cytoplasm of both, tumor and stromal cells. For our analysis only tumor cell expression was used for statistical analysis. We found 56,2% ETS-1 positive tumors, 77,7% were MMP-2 positive, and MMP-9 was expressed in 90% of primary breast carcinomas. There were no significant correlations between MMP-s expression and other patohistological prognostic factors, but expression of ETS-1 was significantly correlated with higher tumor size and grade, as well as with negative steroid receptors. Co-expression of MMP-2, MMP-9 and ETS-1 was found in 40,5 % of tumors, and more commonly was found in tumors larger than 2 cm, high grade tumors, and steroid receptor negative tumors. In univariate analysis, statistically significant negative impact on overall survival (OS) had tumor size, nuclear and tumor grade, ETS-1 expression in tumor cells, co

  18. 子宫内膜腺癌中MMP-2、MMP-9表达的免疫组化研究%Metalloproteinase-9(MMP-9)in Endometrial Adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    仲肖静; 颜丽丽

    2014-01-01

    目的:探讨基质金属蛋白酶-2、-9(Matrix metalloproteinases,MMP)在子宫内膜腺癌组织中的表达及其与临床病理关系。方法:应用免疫组化SP法检测MMP-2、MMP-9在不同子宫内膜组织中的表达情况。结果:MMP-2在正常子宫内膜、子宫内膜增生症和子宫内膜腺癌组织中的阳性表达率分别为15.0%、26.7%、88.0%, MMP-9的阳性表达率分别为25.0%、33.3%、95.0%,MMP-2和MMP-9的表达在子宫内膜腺癌中均明显高于正常子宫内膜、子宫内膜增生症,比较差异均有统计学意义(P<0.05)。MMP-2、MMP-9的表达强度与子宫内膜腺癌的手术-病理分期、组织学分级、肌层浸润和淋巴结转移相关,差异均有统计学意义(P<0.05)。结论:MMP-2、MMP-9在子宫内膜腺癌的发生、发展过程中起促进作用,且两者表达与子宫内膜腺癌的浸润深度和转移程度有关,为早期诊断子宫内膜腺癌以及子宫内膜腺癌的预后判断、靶向治疗提供了可靠的依据。%Objective:To investigate the expression of MMP-2 and MMP-9 in endometrial adenocarcinoma tissue and its relation to clinical pathological characteristics.Method:Expression of MMP-2 and MMP-9 was examined by immunohistochemistry(SP method)in three different kinds of endometrium.Result:The results showed that the positive rates of MMP-2 in normal endometria,endometrial hyperplasias and endometrial adenocarcinomas were 15.0%,26.7%and 88.0%respectively,the positive rates of MMP-9 were 25.0%,33.3%and 95.0%respectively.Expression of MMP-2 and MMP-9 were significantly higher in endometrial adenocarcinoma than those in hyperplastic and normal endometria, the differences were statistically significant(P<0.05).In endometrial adenocarcinoma tissue,the positive expression of MMP-2 and MMP-9 was correlated with clinical pathological characteristics,histodifferentiation,myometrial invasion and lymphatic metastasis,the differences were statistically

  19. Correlation Between Th1, Th2 Cells and Levels of Serum MMP-2, MMP-9 in Children with Asthma

    Directory of Open Access Journals (Sweden)

    Xuan WANG

    2015-12-01

    Full Text Available Abstract Objective: To explore the correlation between Th1 and Th2 cells and the levels of serum matrix metalloproteinase-2 (MMP-2 and MMP-9 in children with asthma. Methods: A total of 89 children with asthma were divided into acute group (n=48 and chronic group (n=41 according to the course of disease, and 40 healthy children at the same term were collected as control group. The ratios of Th1 and Th2 cells as well as levels of MMP-2 and MMP-9 were compared in three groups, and the correlation between Th1 and Th2 cells and levels of MMP-2, MMP-9 was analyzed in acute group and chronic group. Results: When compared with control group, the ratios of Th1 and Th2 cells went down in both acute group and chronic group (P<0.01, while the levels of serum MMP-2 and MMP-9 up (P<0.01. The levels of serum MMP-2 and MMP-9 in acute group were dramatically higher than those in chronic group, and there was statistical significance (P<0.01. Pearson correlation analysis revealed that there was no significant correlation between Th1 and Th2 cells and MMP-2 level (r=0.148, P=0.314, r=0.299, P=0.058; r=0.183, P=0.214, r=0.289, P=0.067, whereas both Th1 and Th2 cells were negatively correlated with MMP-9 level in acute group and chronic group (r=-0.489, P=0.000, r=-0.324, P=0.039; r=-0.352, P=0.014, r=-0.357, P=0.022. Conclusion: Aberrant secretion of Th cells can not only damage the immune function of children with asthma, but also decrease the level of serum MMP-9, consequently affecting the collagen degradation and airway remodeling.

  20. 骨桥蛋白和MMP-2、MMP-9在鼻咽癌中的表达%Over Expression of Osteopontin and MMP-2 MMP-9 in Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    赵冬梅; 李彩云; 于庆凯

    2010-01-01

    目的 探讨骨桥蛋白(OPN)和基质金属蛋白酶2、9(MMP-2、MMP-9)在鼻咽癌组织中的表达及其意义.方法 应用免疫组化二步法,分另别检测OPN和MMP-2、MMP-9在正常对照组(7例)和鼻咽癌(45例)组织中的表达,其中鼻咽癌患者发生颈部淋巴结转移有25例.结果 ①鼻咽癌组织中OPN和MMP-2、MMP-9的阳性率明显高于正常对照组(P<0.05),其中淋巴结转移组表达明显增高(P<0.05).②鼻咽癌中OPN和MMP-2、MMP-9的表达与肿瘤的淋巴结转移相关(P<0.05).结论 OPN和MMP-2、MMP-9可能在鼻咽癌的发生发展和突破基底膜向外扩散及淋巴结转移中起到重要作用.

  1. Study on the Role of MMP-2、MMP-9 in the Metastasis of Breast Cancer%MMP-2、MMP-9在乳腺癌转移中作用的研究

    Institute of Scientific and Technical Information of China (English)

    李治; 帅晓明; 黄韬

    2006-01-01

    目的:了解MMP-2、MMP-9与乳腺癌局部侵袭、淋巴结转移情况的相关性,进而探讨MMP-2、MMP-9在乳腺癌转移发生的作用.方法:用免疫组化染色的方法检测不同患者MMP-2、MMP-9的表达情况,然后进行相关性的分析研究.结果:MMP-2的表达情况与乳腺癌的局部侵袭情况存在显著的相关性(P<0.01),MMP-9的表达情况与乳腺癌的淋巴结转移情况存在显著的相关性(P<0.01).结论:我们认为MMP-2、MMP-9作为MMPs(基质金属蛋白酶家族)中的重要成员,在乳腺癌转移发生过程中有促进作用且作用不同.

  2. Expression and Significance of MMP-9 and TIMP-1 in Malignant Peripheral Nerve Sheath Tumours%MMP-9及TIMP-1在恶性外周神经鞘膜瘤中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    齐云飞; 牟英君; 裴丽霞

    2007-01-01

    目的 探讨恶性外周神经鞘膜瘤(malignant peripheral nerve sheath tumours,MPNST)中基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及组织金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)的表达与病理分级、转移及预后的关系.方法 采用免疫组化S-P法检测MPNST中MMP-9及TIMP-1表达.结果 共检测了58例MPNST,其中MMP-9阳性表达率为89.7%(52/58),TIMP-1阳性表达率是60.3%(35/58).MMP-9蛋白酶的表达与病理学分级、转移率呈正相关,与术后生存率呈负相关;而TIMP-1则相反.结论 MMP-9、TIMP-1与MPNST病理学分级、转移及术后生存期有关,可作为判断恶性外周神经鞘膜瘤恶性程度及预后的可靠指标,为其治疗提供参考价值.

  3. Electronic cigarette exposure triggers neutrophil inflammatory responses.

    Science.gov (United States)

    Higham, Andrew; Rattray, Nicholas J W; Dewhurst, Jennifer A; Trivedi, Drupad K; Fowler, Stephen J; Goodacre, Royston; Singh, Dave

    2016-05-17

    The use of electronic cigarettes (e-cigs) is increasing and there is widespread perception that e-cigs are safe. E-cigs contain harmful chemicals; more research is needed to evaluate the safety of e-cig use. Our aim was to investigate the effects of e-cigs on the inflammatory response of human neutrophils. Neutrophils were exposed to e-cig vapour extract (ECVE) and the expression of CD11b and CD66b was measured by flow cytometry and MMP-9 and CXCL8 by ELISA. We also measured the activity of neutrophil elastase (NE) and MMP-9, along with the activation of inflammatory signalling pathways. Finally we analysed the biochemical composition of ECVE by ultra-high performance liquid chromatography mass spectrometry. ECVE caused an increase in the expression of CD11b and CD66b, and increased the release of MMP-9 and CXCL8. Furthermore, there was an increase in NE and MMP-9 activity and an increase in p38 MAPK activation. We also identified several harmful chemicals in ECVE, including known carcinogens. ECVE causes a pro-inflammatory response from human neutrophils. This raises concerns over the safety of e-cig use.

  4. The role of matrix metalloproteinase MMP-9 and TIMP-2 tissue inhibitor of metalloproteinases as serum markers of bladder cancer.

    Science.gov (United States)

    Ramón de Fata, F; Ferruelo, A; Andrés, G; Gimbernat, H; Sánchez-Chapado, M; Angulo, J C

    2013-09-01

    The diagnosis and molecular staging of bladder cancer based on the detection of gelatinases mRNA (MMP-2 and MMP-9) in peripheral blood circulating and mononuclear cells have shown promising results. We analyze if the determination of the corresponding protein synthesis products makes it possible to diagnose and characterize patients with bladder cancer. Quantification of the serum levels of MMP-2, MMP-9 and TIMP-2 in a series of 42 individuals (31 patients with bladder cancer in different stages and 11 healthy controls) using the ELISA technique was carried out. The determinations were compared between cases and controls (Mann-Whitney U) and between different groups of tumors (Mann-Whitney U or Kruskal-Wallis), according to the clinical-pathological characteristics (age, gender, T category, M category or grade). Diagnostic yield of these markers was evaluated by analysis of the ROC curves. There is a correlation between the determinations of MMP-2 and TIMP-2 (R=.699; P>.0001) and MMP-9 and TIMP-2 (R=.305; P=.049). Patients with bladder cancer have higher levels of MMP-9 (p<0.0001) and TIMP-2 (P=.047) than the controls. Furthermore, the MMP-9/TIMP-2 ratio is also superior in cancer patients (P<.001). Differences were not detected between cancer and controls regarding age (P=.64) or gender (P=.64). Differences were also not detected regarding MMP-2 (P=.35) or MMP-2/TIMP-2 rate (P=.45). Within the cancer patient population, the MMP-2 and MMP-9 values differ according to T category (P=.022 and P=.038, respectively) and those of the TIMP-2 according to M category (P=.036). ROC curve analysis showed that both MMP-9 and the MMP-9/TIMP-2 ratio discriminate patients with cancer and controls, with equivalent diagnostic accuracy (ABC 0.953) and cut offs of 3.93 ng/mL (S 90%; Sp 81%) and 0.053 ng/mL (S 96%; Sp 84%), respectively. The results obtained suggest that both serum MMP-9 and TIMP-2 would have an application in the prediction of the development and progression of

  5. 膀胱癌组织中 MMP-2 MMP-9蛋白表达研究

    Institute of Scientific and Technical Information of China (English)

    刘新郑; 杨锦建; 马长路; 贺付成

    2008-01-01

    目的 探讨膀胱癌组织中MMP-2,MMP-9蛋白的表达及其与膀胱肿瘤恶性程度和侵袭性之间的关系.方法 采用免疫组化方法检测47例膀胱癌及10例正常膀胱组织中MMP-2、MMP~9的表达.结果 与正常对照组相比.膀胱癌组织中MMP-2、MMP-9蛋白的表达明显增高.随肿瘤分级、分期的增高MMP-9和MMP-2的高表达率增高(P<0.05),MMP-2、MMP-9的高表达率同肿瘤分级、分期呈正相关.结论 MMP-2、MMP-9的高表达与膀胱癌的恶性程度有关,在膀胱癌的发生发展中起重要作用,可用于判断膀胱癌恶性程度及预后.

  6. SDF-1/CXCR7 axis enhances ovarian cancer cell invasion by MMP-9 expression through p38 MAPK pathway.

    Science.gov (United States)

    Yu, Yuecheng; Li, Hongmei; Xue, Baoyao; Jiang, Xia; Huang, Kan; Ge, Junli; Zhang, Hongju; Chen, Biliang

    2014-08-01

    Ovarian cancer is an aggressive gynecological malignancy with high metastatic potential. Recently, the CXC receptor (CXCR7) has been identified as a new receptor for stromal-derived factor-1 (SDF-1), and exerts important roles in cancer development. However, its effect on ovarian cancer and the underlying mechanism remain unknown. In this study, we detected abundant CXCR7 expression in ovarian cancer tissues and cells. Moreover, SDF-1 induced dramatically upregulation of CXCR7 mRNA and protein levels, indicating that the SDF-1/CXCR7 axis existed in ovarian cancer. Further analysis confirmed that SDF-1 enhanced cell adhesion and subsequent invasion, which were significantly attenuated when pretreated with CXCR7 small interference RNA (siRNA), indicating the critical function of SDF-1/CXCR7 in cell invasion. Further mechanistic analysis indicated that SDF-1/CXCR7 enhanced cell invasion by matrix metalloproteinase (MMP)-9, as pretreatment with MMP-9 siRNA significantly abrogated a number of invading cells. Additionally, SDF-1/CXCR7 induced phosphorylation of the p38 MAPK pathway, which was accounted for MMP-9 expression as preconditioning with the p38 MAPK inhibitor SB203580 obviously decreased MMP-9 expression. Together, our data implied that SDF-1/CXCR7 enhanced ovarian cancer cell invasion by MMP-9 expression through the p38 MAPK pathway. Thus, these findings confirmed the critical role of SDF-1/CXCR7 during the pathological processes of ovarian cancer and supported its potential targets for further development of antiovarian cancer therapy.

  7. Zymographic patterns of MMP-2 and MMP-9 in the CSF and cerebellum of dogs with subacute distemper leukoencephalitis.

    Science.gov (United States)

    Machado, Gisele F; Melo, Guilherme D; Souza, Milena S; Machado, Andressa A; Migliolo, Daniela S; Moraes, Olívia C; Nunes, Cáris M; Ribeiro, Erica S

    2013-07-15

    Distemper leukoencephalitis is a disease caused by the canine distemper virus (CDV) infection. It is a demyelinating disease affecting mainly the white matter of the cerebellum and areas adjacent to the fourth ventricle; the enzymes of the matrix metalloproteinases (MMPs) group, especially MMP-2 and MMP-9 have a key role in the myelin basic protein fragmentation and in demyelination, as well as in leukocyte traffic into the nervous milieu. To evaluate the involvement of MMPs during subacute distemper leukoencephalitis, we measured the levels of MMP-2 and MMP-9 by zymography in the cerebrospinal fluid (CSF) and in the cerebellum of 14 dogs naturally infected with CDV and 10 uninfected dogs. The infected dogs presented high levels of pro-MMP-2 in the CSF and elevated levels of pro-MMP-2 and pro-MMP-9 in the cerebellar tissue. Active MMP-2 was detected in the CSF of some infected dogs. As active MMP-2 and MMP-9 are required for cellular migration across the blood-brain barrier and any interference between MMPs and their inhibitors may result in an amplification of demyelination, this study gives additional support to the involvement of MMPs during subacute distemper leukoencephalitis and suggests that MMP-2 and MMP-9 may take part in the brain inflammatory changes of this disease.

  8. 2-Deoxy glucose regulate MMP-9 in a SIRT-1 dependent and NFkB independent mechanism.

    Science.gov (United States)

    Edatt, Lincy; Haritha, K; Sruthi, T V; Aswini, P; Sameer Kumar, V B

    2016-12-01

    MMP9 is a member of the family of zinc-containing endopeptidases which degrade various components of the extracellular matrix, thereby regulating matrix remodeling. Since matrix remodeling plays an important role during growth and progression of cancer and considering the fact that, tumor cells switch to aerobic glycolysis as its major energy source, this study was designed to analyze if partial inhibition of glycolysis (the major energy pathway during hypoxia) can be used as a means to control matrix remodeling in terms of MMP9 activity and expression. For this, human epithelial carcinoma cells were treated with glycolytic inhibitor, 2-deoxy glucose (2DG) at sub-lethal concentrations followed by analysis of the expression and activity of MMP2 and MMP9. The experimental findings demonstrate that exposure of cancer cells to glycolytic inhibitor at concentration that does not induce ER stress, downregulates the activity and expression of MMP9 without affecting the expression levels and activity of MMP2. Further mechanistic analysis revealed that the regulation of MMP9 was mediated in a SIRT-1 dependent mechanism and did not alter the NFkB signaling pathway. The overall results presented here, therefore suggest that the use of glycolytic inhibitor, 2DG at concentration that do not affect cell viability or induce ER stress can be an effective strategy to control matrix remodeling.

  9. Pro-MMP-9 upregulation in HT1080 cells expressing CD9 is regulated by epidermal growth factor receptor.

    Science.gov (United States)

    Herr, Michael J; Mabry, Scott E; Jameson, Jessica F; Jennings, Lisa K

    2013-12-06

    Degradation of the surrounding extracellular matrix (ECM) by matrix metalloproteinases (MMPs) drives invasion and metastasis of cancer cells. We previously demonstrated that tetraspanin CD9 expression upregulates pro-MMP-9 expression and release and promotes cellular invasion in a human fibrosarcoma cell line (HT1080). These events were dependent upon the highly functional second extracellular loop of CD9. We report here that the epidermal growth factor receptor (EGFR) tyrosine kinase expression and activity are involved in the CD9-mediated increase in pro-MMP-9 release and cellular invasion. Pro-MMP-9 expression was significantly decreased in a dose-dependent manner using first a broad spectrum receptor tyrosine kinase inhibitor and multiple specific EGFR inhibitors in CD9-HT1080 cells. Furthermore, gefitinib treatment of CD9-HT1080 cells reduced invasion through matrigel. EGFR knockdown using short interfering RNA resulted in decreased pro-MMP-9 expression and release into the media and subsequent cellular invasion without affecting CD9 expression or localization. Conclusively, this study points to EGFR as a key mediator between CD9-mediated pro-MMP-9 release and cellular invasion of HT1080 cells. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Adenylyl cyclase-associated protein-1/CAP1 as a biological target substrate of gelatinase B/MMP-9.

    Science.gov (United States)

    Cauwe, Bénédicte; Martens, Erik; Van den Steen, Philippe E; Proost, Paul; Van Aelst, Ilse; Blockmans, Daniel; Opdenakker, Ghislain

    2008-09-10

    Matrix metalloproteinases (MMPs) are classically associated with the turnover of secreted structural and functional proteins. Although MMPs have been shown to process also a kaleidoscope of membrane-associated substrates, little is known about the processing of intracellular proteins by MMPs. Physiological and pathological cell apoptosis, necrosis and tumor lysis by chemotherapy, radiotherapy or immunological cytotoxicity, are examples of conditions in which an overload of intracellular proteins becomes accessible to the action of MMPs. We used a model system of dying human myelomonocytic cells to study the processing of intracellular protein substrates by gelatinase B/MMP-9 in vitro. Adenylyl cyclase-associated protein-1 or CAP1 was identified as a novel and most efficient substrate of gelatinase B/MMP-9. The presence of CAP1 in the extracellular milieu in vivo was documented by analysis of urine of patients with systemic autoimmune diseases. Whereas no active MMP-9 could be detected in urines of healthy controls, all urine samples of patients with clinical parameters of renal failure contained activated MMP-9 and/or MMP-2. In addition, in some of these patients indications of CAP1 cleavage are observed, implying CAP1 degradation in vivo. The high turnover rate of CAP1 by MMP-9, comparable to that of gelatin as the natural extracellular substrate of this enzyme, may be critical to prevent pathological conditions associated with considerable cytolysis.

  11. Association of Matrix Metalloproteinase-9 (MMP9 Variants with Primary Angle Closure and Primary Angle Closure Glaucoma.

    Directory of Open Access Journals (Sweden)

    Xueli Chen

    Full Text Available Shorter axial length observed in patients with primary angle closure glaucoma (PACG might be due to altered matrix metalloproteinase-9 (MMP9 activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC, and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07 or with PAC/PACG subgroups (Pc > 0.18. Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P 0.47. The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG.

  12. Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Hristina Obradović

    2016-01-01

    Full Text Available Interleukin 17 (IL-17 is a cytokine with pleiotropic effects associated with several inflammatory diseases. Although elevated levels of IL-17 have been described in inflammatory myopathies, its role in muscle remodeling and regeneration is still unknown. Excessive extracellular matrix degradation in skeletal muscle is an important pathological consequence of many diseases involving muscle wasting. In this study, the role of IL-17 on the expression of matrix metalloproteinase- (MMP- 9 in myoblast cells was investigated. The expression of MMP-9 after IL-17 treatment was analyzed in mouse myoblasts C2C12 cell line. The increase in MMP-9 production by IL-17 was concomitant with its capacity to inhibit myogenic differentiation of C2C12 cells. Doxycycline (Doxy treatment protected the myogenic capacity of myoblasts from IL-17 inhibition and, moreover, increased myotubes hypertrophy. Doxy blocked the capacity of IL-17 to stimulate MMP-9 production by regulating IL-17-induced ERK1/2 MAPK activation. Our results imply that MMP-9 mediates IL-17’s capacity to inhibit myoblast differentiation during inflammatory diseases and indicate that Doxy can modulate myoblast response to inflammatory induction by IL-17.

  13. Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation.

    Science.gov (United States)

    Obradović, Hristina; Krstić, Jelena; Kukolj, Tamara; Trivanović, Drenka; Đorđević, Ivana Okić; Mojsilović, Slavko; Jauković, Aleksandra; Jovčić, Gordana; Bugarski, Diana; Santibañez, Juan Francisco

    2016-01-01

    Interleukin 17 (IL-17) is a cytokine with pleiotropic effects associated with several inflammatory diseases. Although elevated levels of IL-17 have been described in inflammatory myopathies, its role in muscle remodeling and regeneration is still unknown. Excessive extracellular matrix degradation in skeletal muscle is an important pathological consequence of many diseases involving muscle wasting. In this study, the role of IL-17 on the expression of matrix metalloproteinase- (MMP-) 9 in myoblast cells was investigated. The expression of MMP-9 after IL-17 treatment was analyzed in mouse myoblasts C2C12 cell line. The increase in MMP-9 production by IL-17 was concomitant with its capacity to inhibit myogenic differentiation of C2C12 cells. Doxycycline (Doxy) treatment protected the myogenic capacity of myoblasts from IL-17 inhibition and, moreover, increased myotubes hypertrophy. Doxy blocked the capacity of IL-17 to stimulate MMP-9 production by regulating IL-17-induced ERK1/2 MAPK activation. Our results imply that MMP-9 mediates IL-17's capacity to inhibit myoblast differentiation during inflammatory diseases and indicate that Doxy can modulate myoblast response to inflammatory induction by IL-17.

  14. Expressions of MMP-2 and MMP-9 during wound healing in rat skin%MMP-2、MMP-9在大鼠皮肤创面愈合过程中的表达

    Institute of Scientific and Technical Information of China (English)

    夏云; 张利远; 徐斌; 陈静; 陈淼

    2012-01-01

    Objective To investigate dynamic changes of metalloproteinase-2 (MMP-2) and MMP-9 expressions during wound healing in rat skin and their correlation. Methods Forty-two rats were used to establish dorsal skin wounds model and equally randomized into seven groups according to the times when the biopsies from skin wounds were harvested at 1,12,24 hours and 3,7,14,21 days after wounds formation, respectively. The other 3 rats were taken as the controls. The expressions of MMP-2 and MMP-9 in the samples were detected by immunohistochemistry. Results MMP-2 and MMP-9 were hardly expressed in normal skins of the control rats. The expression of MMP-2 increased gradually after injury and reached the peak on the 14th day,then decreased gradually to a certain level. The expression of MMP-9 increased rapidly and showed a high level from 24 hours to 7 days after injury, then decreased gradually to a low level. The expression level of MMP-2 was positively correlated to that of MMP-9 at 12 hours and 3,7,14,21 days and negatively correlated at 24 hours after injury. Conclusion The MMP-2 and MMP-9 expressions have certain rule and influence each other during wound healing in rats.%目的 探讨基质金属蛋白酶2 (MMP-2)、MMP-9在大鼠皮肤创面愈合过程中表达的动态及其相关性.方法 42只大鼠制作大鼠背部皮肤创面模型后按取创面皮肤时间随机均分为七组,即在创面形成后1、12、24 h及3、7、14、21d切取背部皮肤创面标本,采用免疫组化法检测标本中MMP-2及MMP-9的表达.另取3只正常大鼠背部皮肤标本作为对照.结果 正常大鼠皮肤中MMP-2、MMP-9几无表达;背部皮肤创面形成后,MMP-2逐渐升高,14 d达峰,21 d仍高于正常水平;MMP-9迅速升高,在24 h-7 d呈高水平表达,后逐渐降至较低水平;MMP-2与MMP-9的表达水平在12h,3、7、14、21d时呈正相关,在24 h时呈负相关.结论 在大鼠创面愈合过程中MMP-2和MMP-9的表达有一定规律,并且二者相互影响.

  15. Expression and significance of MMP-2,MMP-3 and MMP-9 in the gastric carcinoma%MMP-2、MMP-3和 MMP-9在胃癌患者中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    杨云鹏; 刘莉; 李慧

    2016-01-01

    目的:研究 MMP-2、MMP-3和 MMP-9在胃癌细胞转移中作用,进一步探讨 MMP-2、MMP-3和 MMP-9的临床意义。方法体外培养 SGC-7901胃癌细胞和 GES-1胃上皮细胞,划痕损伤实验模型和 Transwell 小室模型法检测这2种细胞的迁移, ELISA 法检测培养液中 MMP-2、MMP-3和 MMP-9的含量。免疫组化检测胃癌、胃炎患者和正常人 MMP-3的阳性率,ELISA 检测血清中 MMP-2、MMP-3和 MMP-9的含量。结果细胞划痕实验和 Transwell 实验均显示,SGC-7901细胞迁移能力强于 GES-1;SGC-7901分泌的3种蛋白含量均高于 GES-1;免疫组化结果显示,胃癌患者 MMP-3的阳性率84.4%,高于胃炎患者和正常人。其血清中 MMP-2、MMP-3和 MMP-9也明显高于胃炎患者和正常人。结论胃癌细胞的转移能力与 MMP-2、MMP-3和 MMP-9的含量相关,3种蛋白可用于胃癌的早期诊断。%Objecitive The research was in order to explore the roles of MMP-2,MMP-3 and MMP 9 which played in the gastric cancer cell metastasis,and make a further study of the clinical signifance.Methods Both SGC-7901 and GES-1 were cultured in vivo.The migra-tion were examined by Wound-healing and the Transwell assay.The expression of MMP-2,MMP-3 and MMP 9 in the medium were detected by ELISA.The positive rate of MMP-3 in the gastric cancer,gastritis and normal was used the IHC,and the serum of MMP-2,MMP-3 and MMP-9 were also examined by ELISA.Results Both Wound-healing and Transwell assay showed that the migration of SGC-7901 cells was more quicker than the GES-1.Comparing to GES-1,the MMP-2,MMP-3 and MMP-9 were higher in the SGC-7901.The immunohistochemical results showed that the positive rate of MMP-3 in the gastric cancer patients was 84.4%,it was higher than the latter.The serum levels of MMP-2 MMP-3 and MMP-9 were also significantly higher than others.Conclusion The migration of gastric cancer cells was depended on the MMP-2,MMP-3 and MMP-9.The 3 proteins can be used

  16. IκB-α、MMP-9在食管癌中的表达及其生物学意义%Expressions of IκB-αand MMP-9 in Esophageal Cancer and Its Biological Significance

    Institute of Scientific and Technical Information of China (English)

    刘亮; 王莉; 倪晓辰; 武中林; 王光大; 赵阳; 左静; 王静; 左连富

    2015-01-01

    Objective To detect the expressions of inhibitor of NF-κB α ( IκB-α) and matrix metalloprotein-9 (MMP-9) protein of nuclear factor kappa B (NF-κB) in different esophageal lesion tissues and to explore the relationship between IκB-α and MMP-9 expressions and pathogenesy, development and metastasis of esophageal cancer. Methods The IκB-α and MMP-9 protein expressions in esophagus squamous cell carcinoma, esophageal atypical hyperplasia and normal esophageal tunica mucosa tissues were detected using immunohistochemistry method;the relationship between the IκB-α and MMP-9 protein expressions in tissues of esophagus squamous cell carcinoma and different clinicopathological features were analyzed as well as the relationship between IκB-αand MMP-9 expressions in tissues of esophagus squamous cell carcinoma. Results The IκB-α protein expression in tissues of esophagus squamous cell carcinoma (80. 0%) was significantly higher than 52. 3% in tissues of esophageal atypical hyperplasia and 8. 3% in normal esophageal tissues, and the differences were statistically significant ( P0. 05). Conclusion The abnormal expressions of IκB-αand MMP-9 protein in esopha-geal cancer is involved in the invasion and metastasis of esophageal cancer.%目的 检测核因子κB(NF-κB)的抑制蛋白α(inhibitor of NF-κB α, IκB-α)及基质金属蛋白酶9(matrix metalloprotein-9,MMP-9)在不同食管病变组织中的表达,探讨IκB-α、MMP-9与食管癌发生、发展及转移的关系. 方法通过免疫组织化学检测食管鳞癌、食管不典型增生组织及食管正常黏膜组织中IκB-α、MMP-9蛋白的表达;分析食管鳞癌组织中IκB-α、MMP-9蛋白表达与不同临床病理特征的关系,并对食管鳞癌组织中IκB-α与MMP-9蛋白表达相关性进行分析. 结果 食管鳞癌组织中IκB-α蛋白的表达(80. 0%)明显高于食管不典型增生组织(52. 3%)及食管正常组织(8. 3%),差异有统计学意义(P0. 05). 结论 IκB-α、MMP

  17. Expressions of MMP-2 and MMP-9 in the Esophageal Squamous-celled Carcinoma%食管鳞癌组织中MMP-2和MMP-9的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    曹婧

    2016-01-01

    目的 探讨食管鳞癌组织中基质金属蛋白酶-2(MMP-2)和MMP-9的表达及临床意义.方法 采用免疫组化S-P法检测105例食管鳞癌和50例癌旁正常食管黏膜组织中MMP-2和MMP-9的表达.结果 食管鳞癌组织中MMP-2和MMP-9的阳性率分别为76.2%(80/105)、71.4% (75/105),癌旁正常食管黏膜组织中分别为6.0% (3/50)、8.0%(4/50),比较差异均有统计学意义( P均<0.05).食管鳞癌组织中MMP-2和MMP-9的表达与分化程度、浸润纤维膜与否、临床分期、淋巴结转移与否有关(P均<0.05).食管鳞癌组织中MMP-2和MMP-9的表达呈正相关关系(r=0.438,P<0.05).结论 MMP-2和MMP-9在食管鳞癌组织中均存在高表达,这与食管癌的疾病进展关系密切.

  18. 肺癌患者血清MMP-9和TIMP-1检测的临床意义%The clinical significance of the measurement of serum MMP-9 and TIMP-1 in patients with lung cancer

    Institute of Scientific and Technical Information of China (English)

    王小军; 火云霞; 刘华; 李伟华; 潘辉; 蔡曦光

    2013-01-01

    Objective To investigate the serum expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of matrix metalloproteinase-l(TIMP-l) in lung cancer patients and healthy people,and its relationship with clinical pathological features, including staging, the degree of tumor differentiation, the size of tumor, the lymph node metastasis status and distant metastasis, etc. Methods The serum expression of MMP-9 and TIMP-1 in lung caner patients and healthy people were tested by ELISA and analyzed statistically. Results The serum expression of MMP-9 and TIMP-1 in lung caner patients were significantly higher than that of healthy people (P0. 05). Conclusion MMP-9 and TIMP-1 may take part in the progress of lung cancer,and could be used as clinical indicators to monitor the development of disease.%目的 研究基质金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制剂-1(TIMP-1)在肺癌患者和健康人血清中的含量,及其与分期、肿瘤分化程度、肿瘤大小、淋巴结转移状态、远处转移等病理特征的相关性.方法 通过酶联免疫吸附测定(ELISA)分别检测肺癌患者和健康对照者的血清样本中的MMP-9、TIMP-1的浓度,进行统计学分析.结果 MMP-9和TIMP-1在肺癌患者血清中的含量明显高于健康人群,差异有统计学意义(P<0.01);并与分期、肿瘤大小、淋巴结转移、远处转移呈正相关(P<0.05),与分化程度呈负相关(P<0.05);而与年龄、性别、吸烟史、肿瘤的病理类型无关(P>0.05).结论 MMP-9和TIMP-1参与肺癌的发生、发展、侵袭转移过程,可作为临床监测病情发展的指标.

  19. Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer.

    Science.gov (United States)

    Dragutinović, Vesna V; Radonjić, Nevena V; Petronijević, Nataša D; Tatić, Svetislav B; Dimitrijević, Ivan B; Radovanović, Nebojša S; Krivokapić, Zoran V

    2011-09-01

    Colorectal cancer is one of the leading causes of cancer related death in developed countries. One of the reasons is the absence of tumor specific diagnostic and prognostic markers. The aim of this study was to examine the correlation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expressions in serum and clinicopathological features of the colorectal adenocarcinoma. Another aim was to examine expression of MMP-9 in the tissue of the colorectal carcinoma in MMP-9 serum positive patients. In addition, we tried to establish the correlation between preoperative levels of serum markers (CEA and CA 19-9) and presence of MMP-2 or MMP-9. The study was performed on 32 patients with colorectal adenocarcinoma who underwent surgery and 11 patients in a control group who were operated for benign diseases. The samples were analyzed by SDS-PAGE to determine the molecular mass and SDS-PAGE zymography to determine levels of MMP-2 and MMP-9. Expression of MMP-9 was determined immunohistochemically in the tissue of the colorectal carcinoma of MMP-9 serum positive patients. MMP-2 and MMP-9 levels were increased in the serum of the patients with colorectal cancer compared to the control group. There was significant correlation in MMPs levels among the patients with tumor stage I and II and the patients with tumor stage III and IV. Obtained results did not demonstrate correlation between levels of CEA, CA 19-9 and presence of MMP-2 or MMP-9. MMP-9 expression was positive in 85% of MMP-9 serum positive patients with colorectal carcinoma. The overexpression of MMP-2 and MMP-9 strongly suggests its association with colorectal adenocarcinoma. Detection of MMP-2 and MMP-9 in serum might be useful for identification of patients with higher risk for colorectal cancer recurrence.

  20. The effect of captopril on the expression of MMP-9 and the prognosis of neurological function in herpes simplex encephalitis mice.

    Science.gov (United States)

    Zhou, Yu; Zeng, Yan-Ping; Zhou, Qin; Guan, Jing-Xia; Lu, Zu-Neng

    2016-08-01

    Early increased matrix metalloproteinase-9 (MMP-9) expression is involved in the evolution of herpes simplex encephalitis (HSE) by facilitating the development of cerebrovascular complications. However, the molecular mechanism underlying the detrimental effects of MMP-9 in HSE has not been elucidated. Recent research finds angiotensin II plays an important role in regulation of MMP-9 activity. The aim of this work was to identify the influence of angiotensin-converting enzyme inhibitor (ACEI) captopril on MMP-9 activation after herpes simplex virus 1 (HSV-1) infection. Animal models of HSE were established by intracerebral inoculation of HSV-1 into mice. Brain tissue ROS levels were measured by staining with dihydroethidium. MMP-9 protein expression was detected by immunofluorescence and brain water content was measured with dry-wet weight method. Neurological function score was quantified 5 d after HSV-1 infection. Microglial cells were treated with various concentrations of captopril. MMP-9 gelatinolytic activity in the supematant of the cell cultures was assessed by zymography. RT-PCR was used to detect the mRNA expressions of p47phox and MMP-9. Immunofluorescence showed that expression of MMP-9 in brain tissue was mainly presented in OX-42 positive microglia. Quantification of gelatinolytic activity by densitometry showed that expression of MMP-9 in microglia was significantly increased after HSV-1 infection and inhibited by captopril treatment. NADPH oxidase subunit p47phox and MMP-9 mRNA expression were significantly increased 6 h after HSV-1 infection, and were seen reduced after captopril treatment in dose dependence. Captopril also downregulated ROS and MMP-9 protein expression following encephalitis in vivo, and attenuated brain edema, and improved neurological function. This compelling evidence suggests that MMP-9 is a key pathogenic factor within HSE. ACEI captopril could reduce the expression of MMP-9 mediated by ROS, then relieve cerebral edema and

  1. Loss of keratinocyte focal adhesion kinase stimulates dermal proteolysis through upregulation of MMP9 in wound healing.

    Science.gov (United States)

    Wong, Victor W; Garg, Ravi K; Sorkin, Michael; Rustad, Kristine C; Akaishi, Satoshi; Levi, Kemal; Nelson, Emily R; Tran, Misha; Rennert, Robert; Liu, Wei; Longaker, Michael T; Dauskardt, Reinhold H; Gurtner, Geoffrey C

    2014-12-01

    To investigate how epithelial mechanotransduction pathways impact wound repair. Mechanical forces are increasingly recognized to influence tissue repair, but their role in chronic wound pathophysiology remains unknown. Studies have shown that chronic wounds exhibit high levels of matrix metalloproteinase 9 (MMP9), a key proteolytic enzyme that regulates wound remodeling. We hypothesized that epithelial mechanosensory pathways regulated by keratinocyte-specific focal adhesion kinase (FAK) control dermal remodeling via MMP9. A standard wound model was applied to keratinocyte-specific FAK knockout (KO) and control mice. Rates of wound healing were measured and tissue was obtained for histologic and molecular analyses. Transcriptional and immunoblot assays were used to assess the activation of FAK, intracellular kinases, and MMP9 in vitro. A cell suspension model was designed to validate the importance of FAK mechanosensing, p38, and MMP9 secretion in human cells. Biomechanical testing was utilized to evaluate matrix tensile properties in FAK KO and control wounds. Wound healing in FAK KO mice was significantly delayed compared with controls (closure at 15 days compared with 20 days, P = 0.0003). FAK KO wounds demonstrated decreased dermal thickness and collagen density. FAK KO keratinocytes exhibited overactive p38 and MMP9 signaling in vitro, findings recapitulated in human keratinocytes via the deactivation of FAK in the cell suspension model. Functionally, FAK KO wounds were significantly weaker and more brittle than control wounds, results consistent with the histologic and molecular analyses. Keratinocyte FAK is highly responsive to mechanical cues and may play a critical role in matrix remodeling via regulation of p38 and MMP9. These findings suggest that aberrant epithelial mechanosensory pathways may contribute to pathologic dermal proteolysis and wound chronicity.

  2. Effect of fluvastatin on inflammatory factors, MMP-9, mAlb, Hcy and APN in patients with early diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    Peng Ye; Dan Li; Li Chen; Xing Chen

    2016-01-01

    Objective:To investigate the effect of fluvastatin on inflammatory factors, MMP-9, mAlb, Hcy and APN in patients with early diabetic nephropathy.Methods:A total of 80 patients with early diabetic nephropathy were randomly divided into diet group (n=40) and fluvastatin group (n=40), and 40 healthy people were regarded as control group. The two groups both received low protein diet, and the fluvastatin group was additionally given fluvastatin. The treatment time of the two groups was 2 months. The levels of inflammatory factors, MMP-9, mAlb, Hcy and APN in the three groups before treatment, after treatment for 1 month, after treatment for 2 months were detected and compared, respectively.Results:Before treatment, the levels of hs-CRP, TNF-α, mAlb, Hcy and MMP-9 in diet and fluvastatin group were significantly higher while the level of APN was significantly lower than that in control group (P0.05), and there was significant difference of all indexes between diet and fluvastatin group (P0.05), while the level of mAlb decreased significantly than that before treatment and after treatment for 1 month in diet group (P<0.05), there were significant differences of the indexes (hs-CRP, TNF-α, MMP-9, Hcy and APN) between diet and fluvastatin group (P<0.05).Conclusions: Early diabetic nephropathy can lead to abnormal the levels of inflammatory factors, MMP-9, mAlb, Hcy and APN, fluvastatin can significantly improve inflammatory factors and the levels of MMP-9, mAlb, Hcy and APN in patients with early diabetic nephropathy.

  3. Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    BACKGROUND: Propofol  is  one  of  the  extensively  and commonly  used  intravenous  anesthetics  and  has  the  ability to  influence  the  proliferation,  motility,  and  invasiveness  of many  cancer  cells.  In  this  study,  the  effects  of  propofol  on hepatocellular carcinoma cells invasion ability were examined. METHODS: We assessed the invasion ability of HepG2 cells in vitro  by  determining  enzyme  activity  and  protein  expression of  MMP-9  using  gelatin  zymography  assay  and  Western  blot. The real-time PCR was used to evaluate the effect of propofol on  microRNA-199a  (miR-199a)  expression,  and  miR-199a-2 precursor  to  evaluate  whether  over-expression  of  miR-199a can affect MMP-9 expression. Finally, the effect of miR-199a on propofol-induced anti-tumor activity using anti-miR-199a was assessed. RESULTS: Propofol  significantly  elevated  the  expression of  miR-199a  and  inhibited  the  invasiveness  of  HepG2  cells. Propofol  also  efficiently  decreased  enzyme  activity  and protein  expression  of  MMP-9.  Moreover,  the  over-expression of miR-199a decreased MMP-9 protein level. Interestingly, the neutralization of miR-199a by anti-miR-199a antibody reversed the effect of propofol on alleviation of tumor invasiveness and inhibition of MMP-9 activity in HepG2 cells. CONCLUSION: Propofol  decreases  hepatocellular  carcinoma cell invasiveness, which is partly due to the down-regulation of MMP-9 expression by miR-199a.

  4. MMP-2、MMP-9及EMMPRIN在子宫内膜异位症中的表达及临床意义%Expression and significance of MMP-2, MMP-9 and VEGF in endometriosis

    Institute of Scientific and Technical Information of China (English)

    车建华; 潘文婧; 刘倩; 谭文华

    2011-01-01

    Objective: To investigate the expression and significance of EMMPRIN, MMP - 2 and MMP - 9 in endometriosis (Ems). Methods: The expression of MMP - 2, MMP - 9 and EMMPRIN in 42 cases of ectopic endometrium, 42 cases of eutopic en-dometrial and 20 cases of normal endometrium were detected by two - step immunohistochemical method, then the correlation of the expression of them was evaluated. Results: The MMP - 2, MMP - 9 and EMMPRIN positive expression rate was 95. 24%、 92. 86% and 90. 48% respectively in the ectopic endometrium group, which were significantly higher than their counterparts in the eutopic endorae-trial group and the normal endometrium group ( P < 0. 05 ) ; there was not significant difference between the eutopic endometrial group and the normal endometrium group. The expression of EMMPRIN protein was positively correlated with MMP - 2, 9 in the ectopic endometrium group (P <0. 01). Conclusion; EMMPRIN, MMP - 2 and MMP -9 are all involved in the process of invasionand tissue remodeling, which is supposed to be part of pathogenesis of endometriosis and EMMPRIN protein plays its role probably through activating MMP - 2, 9 synthesis and secretion.%目的 研究基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、细胞外基质金属蛋白酶诱导因子(EMMPRIN)在子宫内膜异位症(EMs)的表达和意义.方法 应用免疫组化二步法检测EMs患者异位内膜42例、在位内膜42例及正常内膜20例中的MMP-2、MMP-9、EMMPRIN的表达情况,并对它们的EMMPRIN、MMP-2、MMP-9蛋白表达水平进行相关性分析.结果 MMP-2、MMP-9、EMMPRIN在异位内膜组中阳性表达率分别为95.24%、92.86%和90.48%,显著高于在位内膜组、正常内膜组(P<0.05);而在位内膜组和正常内膜组差异无统计学意义(P>0.05).异位内膜组中,EMMPRIN分别和MMP-2,MMP-9呈正相关性(P<0.01).结论 MMP-2、MMP-9、EMMPRIN共同参与了子宫内膜异位症的发生

  5. MMP-2、MMP-9在乳腺导管癌中表达及意义%Expression and significance of MMP-2, MMP-9 in breast carcinoma

    Institute of Scientific and Technical Information of China (English)

    苏书娟; 邢鲁奇; 陈登庭; 邓淼

    2011-01-01

    Objective To research the expression and relationship of matrix metalloproteinase-2 ( MMP-2), metrix metalloproteinase-9(MMP-9) and collagen Ⅳ in breast ductal carcinoma. Methods Immunohistochemistry double staining was used to detect the expression of MMP-2, MMP-9 and collagen Ⅳ in 60 cases of breast ductal carcinoma and analyze their correlation. The relations between MMP-2, MMP-9 and breast ductal carcinoma tumor size, lymph node metastasis, and C-erbB-2 were analyzed. Results The positive expression rate of MMP-2 ,MMP-9 in breast ductal carcinoma was 75% and 80% ,respectively,which were significantly higher than the rate of 10% in normal breast tissues. MMP-2 and MMP-9 were expressed more strongly in the cancer cells approaching the basement membrane or breaking through the basement membrane. The positive expressions of MMP-2 and MMp-9 in the tumor diameter > 2em, with lymph node metastasis, and C-erbB-2 positive group were 83.9% and 90. 3% ,87.0% and 91.3% ,and 80. 9% and 85. 1% ,which were significantly higher than 58.6% and 65.5% ,64. 9% and 67. 6% ,and 46. 2% and 53. 8% of the correponding control groups. Collagen Ⅳ expression and the expression of MMP-2, MMP-9 was negatively correlated. Conclusion The degradation of collagen Ⅳ related to MMP-2 and MMP-9 may play an important role in local invasive and distant metastasis of breast ductal carcinoma. The expressions of MMP-2 ,MMP-9 and collagen Ⅳ may have reference value in determining the invasive and metastatic potential of breast carcinoma and evaluating prognosis.%目的 研究乳腺导管癌中基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的表达及与Ⅳ型胶原(collagenⅣ)的关系.方法 免疫组化双染法检测60例乳腺导管癌中MMP-2、MMP-9和Ⅳ型胶原的表达并分析其相关性及与肿瘤大小、淋巴结转移及人类表皮生长因子受体-2(C-erbB-2)的关系.结果 MMP-2、MMP-9在乳腺导管癌中

  6. 166 Assessment of Chronic Spontaneous Urticaria by Serum-Induced TNF & ALPHA; and MMP-9 Release

    OpenAIRE

    Falkencronec, Sidsel; Poulsen, Lars; Maurer, Marcus; Bindslev-Jensen, Carsten; Skov, Per Stahl

    2012-01-01

    Background Previous studies from our group have demonstrated that IgE-mediated basophil activation leads to release of TNFα that in turn can induce matrix metallo-proteinase-9 (MMP-9) release from monocytes. We wished to investigate if serum from chronic spontaneous urticaria-patients with auto-antibodies against IgE/IgE-receptor could induce TNFα and MMP-9 release from donor PBMCs, and if release levels could be used to assess severity and activity of chronic spontaneous urticaria (CSU). Met...

  7. Effect of Cerium on Expression and Activity of MMP-9 from Human Carcinoma of Bladder Cell Line

    Institute of Scientific and Technical Information of China (English)

    李瑾; 胡国武; 欧阳砥; 牛瑞芳; 周永洽; 申泮文

    2004-01-01

    The effects of Ce4+ on cell survival,expression and activity of matrix metalloproteinase-9(MMP-9)with MTT colorimetry and gelatin zymography assays in human bladder carcinoma cell line was studied.The results indicate that the lower concentration of Ce4+(0.01 mmol*L-1)has no influence on cell growth,but inhibits extremely expression of MMP-9 and increases its activity,whereas the higher concentration of Ce4+(1.0 mmol*L-1)can inhibit all of them.The results raise the possibility that Ce4+ may have beneficial effects in attenuating invasion and metastasis of malignant tumors.

  8. Expression and Clinical Significance of MMP-9 and CD147 in Salivary Adenoid Cystic Carcinoma%MMP-9、CD147在涎腺腺样囊性癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    任洁琼; 赵艳琴; 范熙明; 南欣荣

    2012-01-01

    目的:联合检测人涎腺腺样囊性癌组织中MMP-9、CD147的表达并分析其相关性,探讨其与临床病理参数间的关系,为腺样囊性癌的临床治疗和预后判断提供理论依据.方法:选择山西医科大学第一医院病理科存档的腺样囊性癌组织标本21例(癌组),正常涎腺组织6例(对照组).21例腺样囊性癌分别依据临床分期、有无侵犯神经进行分组.运用免疫组织化学PV-9000二步法检测MMP-9、CD147,结果用SPSS 13.0软件分析.结果:MMP-9及CD147在腺样囊性癌组中的阳性表达率(分别为76.2%和81.0%)明显高于在对照组中的阳性表达率(分别为16.7%和16.7%),差异有统计学意义(分别为P<0.05和P<0.01).Ⅲ+Ⅳ期腺样囊性癌病例MMP-9及CD147的阳性表达率(均为100.0%),明显高于Ⅰ+Ⅱ期病例(分别为44.4%和55.6%),差异有统计学意义(分别为P<0.01和P<0.05).有无侵犯神经的病例组间比较,MMP-9及CD147的表达差异没有统计学意义(P>0.05).MMP-9和CD147在腺样囊性癌组织中均呈阴性、弱阳性、阳性、强阳性表达者分别为4、5、7和3例,表达一致率为90.5%,Kappa值为0.870.结论:MMP-9和CD147均可作为反映腺样囊性癌细胞生物学行为的客观参考指标,其表达与临床分期密切相关,且二者之间的表达有正相关.%Objective: To investigate the expression of matrix metalloproteinase (MMP)-9 and CD147 in human salivary adenoid cystic carcinoma (SACC) tissues and their correlations. Methods: 21 cases of human SACC tissues and 6 cases of normal human salivary tissues were examined by immunohistochemical method. The relationship between the expression and clinical-pathological behaviors was also analyzed. Follow-up data were statistically analyzed. Results: The expression of MMP-9 and CD 147 in SACC tissues was higher than those in normal salivary tissues. Positive expression rate of MMP-9 and CD147 in SACC tissues was 76.2% and 81.0% respectively

  9. Expression of MMP-9 and TIMP-1 in juvenile rats with chronic heart failure%MMP-9、TIMP-1在心力衰竭幼鼠心肌中的表达

    Institute of Scientific and Technical Information of China (English)

    梅峻; 谷丽; 陆凤凤; 杨蓉

    2012-01-01

    Objective To investigate the expression of MMP-9 and TIMP-1 in juvenile rats with chronic heart failure. Methods Male Wistar juvenile rats were randomly assigned to sham operation group and model group. The CHF animal model was induced by Massart PE method. The left ventricular end-diastolic pressure (LVEDP) were monitored by multiple channels electrophysiological apparatus; the expression of MMP-9 and TIMP-1 in myocardium was evaluated by qualitative and semiquantitative immunohistochemical staining; the collagen in left ventricular interstitial tissue was examined by Masson staining. Collagen volume fraction (CVF) and peri vascular collagen area(PVCA) were measured by image analysis. Results Compared with the sham-group, the ventricular mass index(LVMI), CVF, PVCA and the expression of MMP-9 and MMP-9/TIMP-1 in left ventricle increased in model group(P <0.05). Compared with the sham-group, the expression of TIMP-1 in left ventricle decreased in model group. Conclusion The results indicate that disturbed expression of MMP-9/TEMP-1 system may be associated with the development of myocardial remodeling in juvenile rats with congestive heart failure.%目的 探讨基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制因子(TIMP-1)在心力衰竭幼鼠心室重塑中的作用.方法 雄性Wistar幼鼠随机分为二组,对照组(sham)和心力衰竭组(model).采用腹主动脉缩窄法(Massart PE法)[1]对模型组幼鼠制作充血性心力衰竭动物模型,用免疫组化法检测两组幼鼠心室肌中MMP-9、TIMP-1的表达;用多道电生理仪监测2组幼鼠左室舒张末压(LVEDP),用MASSON染色法观察血管周围胶原面积(PVCA),图像分析测量胶原容积分数(CVF).结果 左室舒张末压(LVEDP)、图像分析测量胶原容积分数(CVF)、血管周围胶原面积(PVCA)、MMP-9MMP-9/TIMP-1比值在模型组幼鼠明显高于对照组幼鼠,差别有统计学意义(P<0.01);TIMP-1在模型组幼鼠心肌表达较对照组明显

  10. 二至丸对诱发性乳腺癌组织中VEGF和MMP-9表达的影响%Effect of Erzhi Pills on Expressions of VEGF and MMP-9 in Induced Rat Brest Cancer

    Institute of Scientific and Technical Information of China (English)

    尚广彬; 曾莉萍; 赵益; 张启云; 董伟; 汤喜兰; 徐国良; 朱卫丰; 刘红宁

    2013-01-01

    目的:研究滋阴方二至丸对二甲基苯蒽(DMBA)诱发性乳腺癌大鼠肿瘤组织中血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)表达的影响.方法:60只雌性SD大鼠随机分为空白对照组、DMBA模型组、二至丸高、中、低(6.4,3.2,1.6 g·kg-1)剂量组和三苯氧胺(TAM)组.除空白对照组外,每只大鼠均以致癌剂DMBA诱导(剂量100 mg·kg-1,2次,间隔1周)乳腺癌.诱导第2天开始给予药物干预,每周触诊所有大鼠乳腺肿瘤发生情况并记录体重变化;15周后处死动物,统计各组大鼠乳腺肿瘤的发病率,并采用SP免疫组化法检测各组动物肿瘤组织中VEGF,MMP-9的表达情况.结果:与DMBA模型组比较,二至丸中剂量组和TAM组大鼠乳腺肿瘤平均潜伏期延长(P<0.05),平均肿瘤直径、平均肿瘤体积、平均瘤重显著降低(P<0.05);二至丸中、高剂量组VEGF和MMP-9强阳性率显著性降低(P<0.05),且VEGF与MMP-9的表达呈正相关.结论:滋阴方药二至丸可能通过干预乳腺癌组织中VEGF和MMP-9的表达,抑制乳腺癌生长恶化.%Objective:To explore the effect of Erzhi pills on expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in brest cancer induced by 7,12-dimethylbenz (a) anthrancene (DMBA) in rats.Method:Sixty female SD rats were randomly divided into 6 groups:the blank control group,the DMBA model group,the high,middle,low dose (6.4,3.2,1.6 g ·kg-1,respectively) Erzhi Pills group and tamoxifen (TAM) group.All model rats were induced by DMBA (100 mg ·kg-1,twice,every two weeks),palpated weekly to monitor the progress of the tumor and body weight were also recorded weekly.At the end of trial,the incidence of breast tumors in each group was calculated.And the expressions of VEGF and MMP-9 in breast cancer tissues were detected using immunohistochemical SP method.Result:Comparing with the DMBA model group,the breast cancer incidence,number and volume of

  11. MMP-9和 Fascin 蛋白在口腔扁平苔藓中的表达及相关性研究%Expression and correlation of MMP-9 and Fascin in oral lichen planus

    Institute of Scientific and Technical Information of China (English)

    刘长欢; 金玲; 丁丽娜; 陈英新

    2016-01-01

    Objective To examine the expression and correlation of MMP-9 and Fascin in oral lichen planus(OLP). Methods The expression of MMP-9 and Fascin in 35 cases of normal oral mucosa,45 cases of oral lichen planus and 46 cases of oral squamous cell carcinoma(OSCC)was examined by immunohistochemical technique.The data was analyzed by SPSS,a exact test using software package.Results the expression of MMP-9 in normal oral mucosa,oral lichen pla-nus and oral squamous cell carcinoma rises in turn.The positive rate respectively is 11.4%(4/35)、66.7%(30/45)、89. 1%(41/46),the comparison among groups is statistically significant(P <0.05);The expression of Fascin in normal o-ral mucosa,oral lichen planus and oral squamous cell carcinoma rises in turn.The positive rate respectively is 0%(0/35)、15.6%(7/45)、69.6%(32/46),the comparison among groups is statistically significant(P <0.05);In oral lichen planus,the expression of MMP-9 is positively correlative with that of Fascin(P <0.05).Conclusion MMP-9 and Fas-cin not only respectively paly an important role in cancerous progress of oral lichen planus but also the two factor work together to promote the cancerous progress.%目的:检测 MMP-9和 Fascin 蛋白在口腔扁平苔藓中的表达情况,探讨两者在扁平苔藓发病机制中的作用及相关性。方法采用免疫组化技术检测 MMP-9和 Fascin 蛋白在35例口腔正常黏膜组织、45例口腔扁平苔藓和46例口腔鳞状细胞癌组织中的表达。应用 SPPSS 软件对实验结果进行卡方检验和 Spearman 相关分析。结果MMP-9在口腔正常黏膜组织、口腔扁平苔藓和口腔鳞状细胞癌组织中的表达依次增高,表达率分别为11.4%(4/35)、66.7%(30/45)、89.1%(41/46),组间差别有统计学意义(P <0.05);Fascin 在口腔正常黏膜组织、口腔扁平苔藓和口腔鳞状细胞癌组织中的表达率依次增高表达率分别为0%(0/35)、15.6%(7/45

  12. CIL-102 induces matrix metalloproteinase-2 (MMP-2)/MMP-9 down-regulation via simultaneous suppression of genetic transcription and mRNA stability.

    Science.gov (United States)

    Liu, Wen-Hsin; Chen, Yeh-Long; Chang, Long-Sen

    2012-12-01

    This study explores the CIL-102 suppression mechanism on matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in human leukemia K562 cells. CIL-102 attenuated K562 cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels. Moreover, CIL-102 reduced luciferase activity of MMP-2/MMP-9 promoter constructs and MMP-2/MMP-9 mRNA stability. CIL-102 treatment induced JNK and p38 MAPK activation but reduced the phospho-ERK level. Transfection of constitutively active MEK1 restored MMP-2 and MMP-9 promoter activity in CIL-102-treated cells, while suppression of p38 MAPK/JNK activation abolished CIL-102-induced MMP-2/MMP-9 mRNA decay. CIL-102-induced p38 MAPK/JNK activation led to protein phosphatase 2A-mediated tristetraprolin (TTP) down-regulation. The reduction in TTP-KH-type splicing regulatory protein (KSRP) complexes formation promoted KSRP-mediated MMP-2/MMP-9 mRNA decay in CIL-102-treated K562 cells. Moreover, CIL-102 reduced invasion and MMP-2/MMP-9 expression in breast and liver cancer cells. Taken together, our data indicate that CIL-102 induces MMP-2/MMP-2 down-regulation via simultaneous suppression of genetic transcription and mRNA stability, and suggest a potential utility for CIL-102 in reducing MMP-2/MMP-9-mediated cancer progression.

  13. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. In this work we confirm that placental leukocytes from human term

  14. Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening

    Directory of Open Access Journals (Sweden)

    John J. O'Leary

    2013-01-01

    Full Text Available Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9 as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant and A2780 (cisplatin-sensitive ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.

  15. Purification and characterization of recombinant full-length and protease domain of murine MMP-9 expressed in Drosophila S2 cells

    DEFF Research Database (Denmark)

    Rasch, Morten G; Lund, Ida K.; Illemann, Martin

    2010-01-01

    . No immunoreactivity was observed when the antibody was probed against skin wound material from MMP-9 deficient mice. In conclusion, we have generated and purified two proteolytically active recombinant murine MMP-9 protein constructs, which are critical reagents for future cancer drug discovery studies....... MMP-9. Constructs encoding zymogens of full-length murine MMP-9 and a version lacking the O-glycosylated linker region and hemopexin domains were therefore generated and expressed in stably transfected Drosophila S2 insect cells. After 7 days of induction the expression levels of the full...

  16. Matrix Metalloproteinase-3 (MMP-3 Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Directory of Open Access Journals (Sweden)

    Arturo Flores-Pliego

    Full Text Available The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9 it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation.Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence.Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05, when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05 and up to 72 h (P≤0.001, when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005 when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells.In this work we confirm that placental leukocytes from

  17. Expression of CD147 protein and MMP-9 and the significance in patients with adenomyosis%CD147蛋白和MMP-9在子宫腺肌病中的表达和意义

    Institute of Scientific and Technical Information of China (English)

    邹宁; 任云青; 李培莉; 薛丽萍

    2011-01-01

    Objective:To study the expression of CD147 and MMP-9 protein in patients with adenomyosis as well as their serun levels of soluble CD 147 in order to investigate their roles in the pathogenesis of adenomyosis. Methods: Immunohistochemistry was performed to dezect the expression of CD147 and MMP-9 protein in ectopic endometrium and eutopic endometrial tissues of 37 patients with adenomyosis(AM group) and endometrial tissues of 20 patients only with hysteromyoma( control group). The correlation between the expressions of CD147 and MMP-9 protein was evaluated. ELISA was used to detect the level of soluble CD147 proteins in the peripheral blood of AM group (37 cases with adenomyosis)and control groups(20 cases with hysteromyoma and 20 healthy cases). Results:The expression of CD147 and MMP-9 proteins in glandular and stromal cells in ectopic and eutopic endometrium of the patients with AM were significantly higher than in control group( P < 0.01 ), and the expression of CD147 and MMP-9 protein was much higher in ectopic endometrium than in eutopic endometrium of the patients with AM.The expression of CD147 protein was positively correlated with MMP-9 in patient with AM.The serum levels of soluble CD147 was much higher in AM groups than in both control group with hysteromyoma ( P > 0.05) and healthy group ( P < 0.05). Conclusion: The higher expression of CD147 protein and MMP-9 in ectopic and eutopic endometrium and serum levels of sCD147 may play an important role in the pathogenesis of AM,and CD147 protein plays its role probably through activating MMP-9 synthesis and secretion.%目的:研究CD147蛋白、MMP-9在子宫腺肌病患者组织中的表达及血清中可溶性CD147(sCD147)蛋白水平,探讨其在子宫腺肌病中的作用机制.方法:采用免疫组织化学SP法检测37例子宫腺肌病患者(子宫腺肌病组)子宫异位内膜、在位内膜及20例子宫肌瘤患者(对照组)子宫内膜组织中CD147蛋白和MMP-9的表达,并对其蛋

  18. Concentration Kinetics of Serum MMP-9 and TIMP-1 after Blunt Multiple Injuries in the Early Posttraumatic Period

    Directory of Open Access Journals (Sweden)

    M. Brumann

    2012-01-01

    Full Text Available Metalloproteinases are secreted in response to a variety of inflammatory mediators and inhibited by tissue inhibitors of matrixmetalloproteinases (TIMPs. Two members of these families, MMP-9 and TIMP-1, were differentially expressed depending on clinical parameters in a previous genomewide mRNA analysis. The aim of this paper was now to evaluate the posttraumatic serum levels and the time course of both proteins depending on distinct clinical parameters. 60 multiple traumatized patients (ISS > 16 were included. Blood samples were drawn on admission and 6 h, 12 h, 24 h, 48 h, and 72 h after trauma. Serum levels were quantified by ELISA. MMP-9 levels significantly decreased in the early posttraumatic period (P<0.05 whereas TIMP-1 levels significantly increased in all patients (P<0.05. MMP-9 and TIMP-1 serum concentration kinetics became manifest in an inversely proportional balance. Furthermore, MMP-9 presented a stronger decrease in patients with severe trauma and non-survivors in contrast to minor traumatized patients (ISS ≤ 33 and survivors, initially after trauma.

  19. A novel ameloblastoma cell line (AM-3) secretes MMP-9 in response to Wnt-3a and induces osteoclastogenesis.

    Science.gov (United States)

    Kibe, Toshiro; Fuchigami, Takao; Kishida, Michiko; Iijima, Mikio; Ishihata, Kiyohide; Hijioka, Hiroshi; Miyawaki, Akihiko; Semba, Ichiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Shosei

    2013-06-01

    Ameloblastoma has a high risk of bone invasion and local recurrence. However, the mechanisms of bone invasion in ameloblastoma remain unclear. In this study, we established an experimental model for matrix metalloproteinase (MMP) induction and osteoclastogenesis using ameloblastoma-derived cells. We established an ameloblastoma-derived cell line without viral genes and analyzed the expression of all Wnt and Frizzled members and MMPs by real-time reverse transcription-polymerase chain reaction, and analyzed the activity of MMP-2 and MMP-9 by the in-gel-gelatinase assay. AM-3, newly established ameloblastoma-derived cells retained the morphology of primary-cultured ameloblastoma cells. AM-3 cells overexpressed the messenger RNA of Wnt-5a, Frizzled-2, MMP-2, and MMP-9 and showed the potential of osteoclastogenesis. In addition, Wnt-3a-treatment induced expression and activation of MMP-9 in AM-3 cells. Our study suggests that AM-3 cells retained the characteristics of ameloblastoma, without acquiring typical features of cancer cells. Furthermore, Wnt signaling induced MMP-9 in ameloblastoma cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. X-ray imaging of differential vascular density in MMP-9-/-, PAR-1-/+, hyperhomocysteinemic (CBS-/+) and diabetic (Ins2-/+) mice.

    Science.gov (United States)

    Givvimani, S; Sen, U; Tyagi, N; Munjal, C; Tyagi, S C

    2011-02-01

    Although protease activated receptor-1 (PAR-1) and matrix metalloproteinase-9 (MMP-9) play significant role in vascular remodelling in hyperhomocysteinemia (HHcy due to cystathionine beta synthase deficiency, CBS-/+) and diabetes, mechanism remains nebulous. We hypothesized that differential vascular density and remodelling in different vascular beds in HHcy and diabetes were responsible for an adaptive metabolic homeostasis during the pathogenesis. To test this hypothesis, vascular density in mice lacking PAR-1, MMP-9, CBS and Insulin-2 gene mutant (Ins2-/+, Akita) was measured and compared with wild type (WT, C57BL/6J) mice. The vascular density was detected by x-ray angiography using KODAK 4000 MM image station, using barium sulphate as contrasting agent. The % vascular density in the hearts of WT, CBS-/+ (HHcy), MMP-9-/-, PAR-1-/+ and Ins2-/+ (type-1 diabetes) was 100 ± 2.8, 85 ± 3.3, 90 ± 3.3, 95 ± 3.8 and 73 ± 1.7, respectively. The vascular density in CBS-/+ and Akita hearts decreased while it was increased in lungs of CBS-/+ and MMP-9-/-.There was decreased vascular density in liver and kidney of Akita mice. Vascular density in brain, kidney and mesentery was decreased in CBS-/+ mice. These findings support the notation that metabolic derangement in diabetes and HHcy causes the chronic decline and/or rarefaction in vascular density.

  1. An ex vivo study on immunohistochemical localization of MMP-7 and MMP-9 in temporomandibular joint discs with internal derangement

    Directory of Open Access Journals (Sweden)

    C. Loreto

    2013-04-01

    Full Text Available Internal derangement (ID is among the most common disorders of the temporomandibular joint (TMJ. Previous research by our group highlighted a correlation between apoptosis and TMJ ID. Metalloproteinases (MMP-7 and -9 have been shown to play an important role in extracellular matrix ECM homeostasis and, through it, in joint disc remodelling. The immunohistochemical expression of MMP-7 and -9 was investigated in discs from patients with TMJ ID and from healthy donors and compared with the degree of histological tissue degeneration. The collagen fibre arrangement in pathological discs exhibited varying degrees of disruption. New vessels were consistently detected; endothelial cells from these vessels were immunolabelled with both MMP-7 and MMP-9. More or less intense MMP-7 and MMP-9 immunolabelling was detected in the cytoplasm of disc cells from all patients. MMP-7 and MMP-9 immunostaining was significantly different between pathological and normal discs and correlated with the extent of histopathological degeneration. MMP-7 and MMP-9 upregulation in discs from patients with TMJ ID demonstrates their involvement in disc damage in this disorder. A greater understanding of these processes could help identify ways to curb MMP overproduction without affecting their tissue remodelling action. The design of specific inhibitors for these MMPs would not only help to gain insights into the biological roles of MMPs, but would also aid in developing therapeutic interventions for diseases associated with abnormal ECM degradation.

  2. Matrix metalloproteinase (MMP)-2 and MMP-9 as inflammation markers of Trichinella spiralis and Trichinella pseudospiralis infections in mice.

    Science.gov (United States)

    Bruschi, F; Bianchi, C; Fornaro, M; Naccarato, G; Menicagli, M; Gomez-Morales, M A; Pozio, E; Pinto, B

    2014-10-01

    Trichinella spiralis and Trichinella pseudospiralis exhibit differences in the host-parasite relationship such as the inflammatory response in parasitized muscles. Several studies indicate that matrix metalloproteinases (MMPs) represent a marker of inflammation since they regulate inflammation and immunity. The aim of this study was to evaluate the serum levels of gelatinases (MMP-9 and MMP-2) in mice experimentally infected with T. spiralis or T. pseudospiralis, to elucidate the involvement of these molecules during the inflammatory response to these parasites. Gelatin zymography on SDS polyacrilamide gels was used to assess the serum levels and in situ zymography on muscle histological sections to show the gelatinase-positive cells. In T. spiralis infected mice, the total MMP-9 serum level increased 6 days post-infection whereas, the total MMP-2 serum level increased onward. A similar trend was observed in T. pseudospiralis infected mice but the MMP-9 level was lower than that detected in T. spiralis infected mice. Significant differences were also observed in MMP-2 levels between the two experimental groups. The number of gelatinase positive cells was higher in T. spiralis than in T. pseudospiralis infected muscles. We conclude that MMP-9 and MMP-2 are markers of the inflammatory response for both T. spiralis and T. pseudospiralis infections.

  3. Oxygen-Loaded Nanodroplets Effectively Abrogate Hypoxia Dysregulating Effects on Secretion of MMP-9 and TIMP-1 by Human Monocytes

    Directory of Open Access Journals (Sweden)

    Giulia Rossana Gulino

    2015-01-01

    Full Text Available Monocytes play a key role in the inflammatory stage of the healing process. To allow monocyte migration to injured tissues, the balances between secreted matrix metalloproteinases (MMPs and their inhibitors (TIMPs must be finely modulated. However, a reduction of blood supply and local oxygen tension can modify the phenotype of immune cells. Intriguingly, hypoxia might be targeted by new effective oxygenating devices such as 2H,3H-decafluoropentane- (DFP- based oxygen-loaded nanodroplets (OLNs. Here, hypoxia effects on gelatinase/TIMP release from human peripheral monocytes were investigated, and the therapeutic potential of dextran-shelled OLNs was evaluated. Normoxic monocytes constitutively released ~500 ng/mL MMP-9, ~1.3 ng/mL TIMP-1, and ~0.6 ng/mL TIMP-2 proteins. MMP-2 was not detected. After 24 hours, hypoxia significantly altered MMP-9/TIMP-1 balance by reducing MMP-9 and increasing TIMP-1, without affecting TIMP-2 secretion. Interestingly OLNs, not displaying toxicity to human monocytes after cell internalization, effectively counteracted hypoxia, restoring a normoxia-like MMP-9/TIMP-1 ratio. The action of OLNs was specifically dependent on time-sustained oxygen diffusion up to 24 h from their DFP-based core. Therefore, OLNs appear as innovative, nonconventional, cost-effective, and nontoxic therapeutic tools, to be potentially employed to restore the physiological invasive phenotype of immune cells in hypoxia-associated inflammation.

  4. Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors.

    Directory of Open Access Journals (Sweden)

    Svantje Tauber

    Full Text Available The cannabinoid system is known to be involved in the regulation of inflammatory processes. Therefore, drugs targeting cannabinoid receptors are considered as candidates for anti-inflammatory and tissue protective therapy. We demonstrated that the prototypical cannabinoid agonist R(+WIN55,212-2 (WIN reduced the secretion of matrix metalloproteinase-9 (MMP-9 in a murine model of cigarette-smoke induced lung inflammation. In experiments using primary cells and cell lines of the monocyte-macrophage-system we found that binding of the cannabinoid-receptor agonist WIN to a stereo-selective, specific binding site in cells of the monocyte-macrophage-system induced a significant down-regulation of MMP-9 secretion and disturbance of intracellular processing, which subsequently down-regulated MMP-9 mRNA expression via a ERK1/2-phosphorylation-dependent pathway. Surprisingly, the anti-inflammatory effect was independent from classical cannabinoid receptors. Our experiments supposed an involvement of TRPV1, but other yet unidentified sites are also possible. We conclude that cannabinoid-induced control of MMP-9 in the monocyte-macrophage system via a cannabinoid-receptor independent pathway represents a general option for tissue protection during inflammation, such as during lung inflammation and other diseases associated with inflammatory tissue damage.

  5. MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors.

    Science.gov (United States)

    Jinga, D C; Blidaru, A; Condrea, Ileana; Ardeleanu, Carmen; Dragomir, Cristina; Szegli, G; Stefanescu, Maria; Matache, Cristiana

    2006-01-01

    The goal of our study was to analyse the prognostic values for some matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in breast cancer. We evaluated the activity and the expression levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 in malignant versus benign fresh breast tumor extracts. For this purpose, gelatinzymography, immunoblotting and ELISA were used to analyse the activity and expression of MMPs and TIMPs. We found that MMP-9 expression level and activity are increased in malignant tumors. In addition, MMP-9/TIMP-1 and MMP-2/TIMP-2 ratio values obtained by us were significantly different in malignant tumors compared to benign tumors. We suggest that the abnormal MMP-9/TIMP-1 balance plays a role in the configuration of breast invasive carcinoma of no special type and also in tumor growth, while altered MMP-2/TIMP-2 ratio value could be associated with lymph node invasion and used as a prognostic marker in correlation with Nottingham Prognostic Index. Finally, we showed that in malignant tumors high expression of estrogen receptors is associated with enhanced activity of MMP-2 and increased bcl- 2 levels, while high expression of progesterone receptors is correlated with low TIMP-1 protein levels.

  6. Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion.

    Science.gov (United States)

    Sapharikas, Elene; Lokajczyk, Anna; Fischer, Anne-Marie; Boisson-Vidal, Catherine

    2015-06-30

    Critical limb ischemia (CLI) induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate. Monocytes negatively isolated with magnetic beads from peripheral blood of healthy donors were treated with fucoidan. Fucoidan induced a 1.5-fold increase in monocyte adhesion to gelatin (p Fucoidan also enhanced migration 2.5-fold in a transmigration assay (p fucoidan (p fucoidan-treated monocytes showed upregulation of ERK/p38 phosphorylation. Inhibition of ERK/p38 phosphorylation abrogated fucoidan enhancement of migration (p Fucoidan displays striking biological effects, notably promoting monocyte adhesion and migration. These effects involve the ERK and p38 pathways, and increased MMP9 activity. Fucoidan could improve critical limb ischemia by promoting monocyte recruitment.

  7. TGF superfamily and MMP2, MMP9, TIMP1 genes expression in the endometrium of women with impaired reproduction.

    Directory of Open Access Journals (Sweden)

    Przemysław Wirstlein

    2008-04-01

    Full Text Available During the putative "implantation window", a period of maximal endometrial receptivity that spans 7-9 days after ovulation, a series of changes on the structural and molecular level occur that render the endometrium susceptible to implantation for the human embryo. Many members of the TGFbetas are expressed by human endometrium at different stages of menstrual cycle. Also studies regarding the MMP2 gene expression and activity of MMP2 in the implantation window have shown a higher expression and activity of MMP2 in women with impaired fertility. We have examined by RT-PCR the expression of TGFbeta2 and MMP2, MMP9 and TIMP1 in 28 patients with idiopathic infertility, 16 patients with unexplained recurrent miscarriage and 16 control women were enrolled in this study. Seven to nine days after ovulation endometrial biopsy by Pipelle or hysteroscopy was performed to assess the expression of TGFbeta2 , MMP2, MMP9 and TIMP1. We found that in endometria from women with idiopathic infertility TGFbeta2 expression was 2.8 fold higher than in endometria from control group and 2.1 fold higher in endometrial samples from women with unexplained recurrent miscarriage compared to the control group. The MMP2, MMP9 and TIMP1 expression in endometrial samples revealed no significant differences between the study groups and control group. There was a statistically significant negative correlation between TGFbeta2 and MMP9 expression in endometria from women in control group. The present investigations suggest that dysregulated TGFbeta2, MMP2, MMP9 and TIMP1 expression are associated with infertility and early pregnancy loss. However the exact mechanism of how overexpression of endometrial TGFbetaand MMPs interferes with implantation may be more complex.

  8. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  9. Spatio-temporal expression of MMP-2, MMP-9 and tissue kallikrein in uteroplacental units of the pregnant guinea-pig (Cavia porcellus

    Directory of Open Access Journals (Sweden)

    Rey Sergio

    2007-07-01

    Full Text Available Abstract Background In humans trophoblast invasion and vascular remodeling are critical to determine the fate of pregnancy. Since guinea-pigs share with women an extensive migration of the trophoblasts through the decidua and uterine arteries, and a haemomonochorial placenta, this species was used to evaluate the spatio-temporal expression of three enzymes that have been associated to trophoblast invasion, MMP-2, MMP-9 and tissue kallikrein (K1. Methods Uteroplacental units were collected from early to term pregnancy. MMP-2, MMP-9 and K1 were analysed by immunohistochemistry and Western blot. The activities of MMP-2 and MMP-9 were assessed by gelatin zymography. Results Immunoreactive MMP-2, MMP-9 and K1 were detected in the subplacenta, interlobar and labyrinthine placenta, syncytial sprouts and syncytial streamers throughout pregnancy. In late pregnancy, perivascular or intramural trophoblasts expressed the three enzymes. The intensity of the signal in syncytial streamers was increased in mid and late pregnancy for MMP-2, decreased in late pregnancy for MMP-9, and remained stable for K1. Western blots of placental homogenates at days 20, 40 and 60 of pregnancy identified bands with the molecular weights of MMP-2, MMP-9 and K1. MMP-2 expression remained constant throughout gestation. In contrast, MMP-9 and K1 attained their highest expression during midgestation. Placental homogenates of 20, 40 and 60 days yielded bands of gelatinase activity that were compatible with MMP-2 and MMP-9 activities. ProMMP-2 and MMP-9 activities did not vary along pregnancy, while MMP-2 and MMP-9 increased at 40 and 40–60 days respectively. Conclusion The spatio-temporal expression of MMPs and K1 supports a relevant role of these proteins in trophoblast invasion, vascular remodeling and placental angiogenesis, and suggests a functional association between K1 and MMP-9 activation.

  10. 胃癌DNA倍体分析及TIMP-2和MMP-9的表达%ANALYSIS OF DNA PLOIDY AND EXPRESSIONS OF TIMP-2 AND MMP-9 IN PATIENTS WITH GASTRIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张景芳; 张原平; 苗芳; 纪祥瑞

    2007-01-01

    目的 检测胃癌DNA倍体及基质金属蛋白酶抑制因子-2(TIMP-2)和基质金属蛋白酶-9(MMP-9)在胃癌中的表达,以探讨胃癌侵袭转移的分子基础和机制.方法 采用免疫组织化学方法检测MMP-9和TIMP-2在99例胃癌、16例癌周黏膜、16例胃癌远处转移灶和25例胃癌淋巴结转移灶标本中的表达情况;采用流式细胞术检测其中47例胃癌、6例癌周黏膜及4例胃癌远处转移灶标本的DNA倍体及S期分数.结果 MMP-9的表达与LAUREN分型、BORRMANN分型、淋巴结转移、转移部位、浸润深度和肿瘤TNM分期有关(χ2=6.65~8.03,P<0.05、0.01);TIMP-2表达与BORRMANN分型、淋巴结转移和浸润深度有关(χ2=5.01~7.05,P<0.05);DNA异倍体率与分化和淋巴结转移有关(χ2=5.083、11.750,P<0.05),S期分数与肿瘤大小、分化和淋巴结转移有关(χ2=4.931~6.299,P<0.05);MMP-9和TIMP-2间存在正相关关系(r=0.22,P<0.05);MMP-9表达、DNA异倍体率和S期分数在胃癌与癌周非癌黏膜间表达的差异具有统计学意义.结论 MMP-9和TIMP-2的异常表达尤其二者间的失衡及DNA异倍体和高S期分数参与了肿瘤的演进和异质化过程.

  11. 牙周病大鼠正畸源性牙根吸收和MMP-9表达的观察%Expression of MMP-9 and root resorption by orthodontic force in rats with periodontal disease

    Institute of Scientific and Technical Information of China (English)

    王月; 王明洁; 常悦; 崔淑霞

    2015-01-01

    目的:探讨牙周病大鼠不同正畸条件下牙根吸收情况与牙组织中基质金属蛋白酶9(MMP-9)表达水平的变化.方法:取108只大鼠,54只制作大鼠牙周病模型,模型制备成功后分别给予0、50和80 g正畸力牵拉1、7、14 d,每个条件下6只大鼠;另54只给予相同正畸处理但不制备牙周病模型(对照组).以上颌切牙为支抗,分别牵拉左侧上颌第一磨牙向近中移动.取各组大鼠实验牙制作组织切片,观察牙根吸收情况,应用免疫组化染色观察MMP-9的表达.结果:50或80 g正畸力牵拉7d后,两组大鼠牙周膜均排列紊乱,可见明显的牙根吸收现象,牙周病组大鼠牙根吸收情况较对照组严重;牵拉14 d后牙根吸收活动基本停止.随着正畸力的增加,MMP-9表达水平逐渐升高;牵拉7d后MMP-9表达水平最高,14 d后下降;牙周病组牙组织中MMP-9表达水平高于对照组(F组别=3.031,P=0.022;F正畸力=6.634,P=0.014;F时间=4.820,P=0.009;F交互=0.890,P=0.514).结论:牙组织中MMP-9表达水平可能能反映牙周病大鼠牙根吸收的程度.

  12. Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling.

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    Linda M Bradley

    Full Text Available The early inflammatory response to influenza virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which neutrophils gain entry to the respiratory tract and their role during pathogenesis remain unclear. Here, we report that neutrophils significantly contributed to morbidity in a pathological mouse model of influenza virus infection. Using extensive immunohistochemistry, bone marrow transfers, and depletion studies, we identified neutrophils as the predominant pulmonary cellular source of the gelatinase matrix metalloprotease (MMP 9, which is capable of digesting the extracellular matrix. Furthermore, infection of MMP9-deficient mice showed that MMP9 was functionally required for neutrophil migration and control of viral replication in the respiratory tract. Although MMP9 release was toll-like receptor (TLR signaling-dependent, MyD88-mediated signals in non-hematopoietic cells, rather than neutrophil TLRs themselves, were important for neutrophil migration. These results were extended using multiplex analyses of inflammatory mediators to show that neutrophil chemotactic factor, CCL3, and TNFα were reduced in the Myd88⁻/⁻ airways. Furthermore, TNFα induced MMP9 secretion by neutrophils and blocking TNFα in vivo reduced neutrophil recruitment after infection. Innate recognition of influenza virus therefore provides the mechanisms to induce recruitment of neutrophils through chemokines and to enable their motility within the tissue via MMP9-mediated cleavage of the basement membrane. Our results demonstrate a previously unknown contribution of MMP9 to influenza virus pathogenesis by mediating excessive neutrophil migration into the respiratory tract in response to viral replication that could be exploited for therapeutic purposes.

  13. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Struckmann, K; Mertz, Kd; Steu, S;

    2008-01-01

    Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression of CXCR4 chemokine receptor, which triggers expression of metastasis-associated MMP2/MMP9 in different human cancers. The impact of pVHL on MMP2/MMP9 expression and their relationship...

  14. Purification and characterization of recombinant full-length and protease domain of murine MMP-9 expressed in Drosophila S2 cells

    DEFF Research Database (Denmark)

    Rasch, Morten G; Lund, Ida K; Illemann, Martin;

    2010-01-01

    MMP-9. Constructs encoding zymogens of full-length murine MMP-9 and a version lacking the O-glycosylated linker region and hemopexin domains were therefore generated and expressed in stably transfected Drosophila S2 insect cells. After 7 days of induction the expression levels of the full...

  15. 下肢曲张静脉壁MMP-2、MMP-9和胶原含量的临床研究%Clinical study of MMP-2, MMP-9 and collagen in lower limb varicose veins

    Institute of Scientific and Technical Information of China (English)

    邵拥军; 朱化刚; 周静

    2012-01-01

    目的研究曲张大隐静脉管壁基质金属蛋白酶(MMP)-2、MMP-9的表达及其与临床症状和体征分期的关系,并检测曲张静脉壁总的胶原含量,探讨MMP-2、MMP-9和胶原在曲张静脉重塑时的作用.方法采用免疫组化SP法检测曲张静脉壁和正常大隐静脉壁MMP-2和MMP-9的表达,采用Masson染色法检测曲张静脉壁和正常对照组总的胶原含量,采用χ2检验和t检验进行统计学分析处理.结果 MMP-2和MMP-9在正常静脉壁和曲张静脉壁均有表达,但曲张静脉壁MMP-2和MMP-9的阳性率明显升高(P<0.05);C4-C6期MMP-2和MMP-9的阳性率明显高于C1-C3期(P<0.05);曲张静脉壁总的胶原含量显著高于正常对照组(P<0.05).结论 MMP-2、MMP-9的异常表达导致了静脉壁总的胶原含量增加,参与了曲张静脉的重塑.%Objective To investigate the expression of matrix metalloproteinase -2 and -9 in varicose veins, and their relationships with clinical stages , and to discuss the changes of total collagen in varicose veins, and their significance. Methods The expression of MMP-2 and MMP-9 was examined by immunohistochemistry SP methods in varicose veins (VV) and normal veins (NVV), the total collagen was detected using Masson staining in varicose veins and normal veins, and chi-square test and T- test was used for statistical analysis. Results MMP-2 and -9 were both expressed in NVV and VV, and the positive expression rate in VV was significantly higher than that in NVV (P< 0.05). The positive expression of MMP-2 and -9 was significantly higher in C4-C6 stages than in C1-C3 stages (P <0.05), and the collagen was significantly increased in varicose veins (P <0.05). Conclusion The abnormal expression of MMP-2 and -9 leads to collagen increasing in varicose veins, which may participate in vascular remodeling in varicose veins.

  16. The regulating role of mutant IκBα in expression of TIMP-2 and MMP-9 in human glioblastoma multiform

    Institute of Scientific and Technical Information of China (English)

    HU Yu-hua; YU Li-Jie; SHAO En-de; WU Jian-liang; JI Jian-wen

    2009-01-01

    Background Our previous studies demonstrated that mutant IκBα (IκBαM) inhibited the occurrence, growth and angiogenesis of human glioblastoma multiform (GBM). However, the specific mechanism by which IKBαM regulates protein-degrading enzymes secreted from GBM to inhibit invasion and metastasis has remained unclear. The aim of the present study was to investigate the regulatory role and significance of IκBαM genes in the expression of tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in human GBM. Methods We established the following four GBM cell lines stably expressing IκBαM by plasmid construction, gene transfection and screening for IκBαM protein expression: mutant IκBα-transfected cells (G36△-M), wild-type IκBα-transfected cells (G36△-W), empty plasmid transfected cells (G36△-P) and untransfected cells (G36△). The TIMP-2 and MMP-9 expression was detected by RT-PCR and Western blotting. Tumor cells were then implanted subcutaneously into nude mice to establish an animal model of ectopic tumor growth, and TIMP-2 and MMP-9 expression was determined by immunohistochemical methods. Results The results showed that there was a significant increase in TIMP-2 expression and a significant decrease in MMP-9 expression in the G36A-M group at both the RNA and protein levels compared with the G36A-W group, G36△-P group and G36△ group. Similar results were observed in the immunohistochemical staining analysis of tumor tissues. In the G36A-M group, TIMP-2 expression was significantly higher while MMP-9 expression was significantly lower than in the other three groups. Conclusions Our findings indicate that IκBαM inhibits the activation of NF-κB. It significantly up-regulates TIMP-2 expression in human malignant glioma cells and down-regulates the expression of MMP-9. Thus, IκBαM maintains the integrity of the extracellular matrix and further inhibits the growth and metastasis of tumor tissues.

  17. A novel cantharidin analog N-Benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji-Yeon; Chung, Tae-Wook; Choi, Hee-Jung [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Lee, Chang Hyun [Department of Anatomy, College of Korean Medicine, Woosuk University, Wanju-gun, Jeonbuk (Korea, Republic of); Eun, Jae Soon; Han, Young Taek [College of Pharmacy, Woosuk University, Wanju-gun, Jeonbuk (Korea, Republic of); Choi, Jun-Yong [Department of Internal Medicine, Korean Medicine Hospital, School of Korean Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of); Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Kim, So-Yeon; Han, Chang-Woo [Department of Internal Medicine, Korean Medicine Hospital, School of Korean Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of); Jeong, Han-Sol, E-mail: jhsol33@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Ha, Ki-Tae, E-mail: hagis@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of)

    2014-05-02

    Highlights: • We examined the inhibition of N-Benzylcantharidinamide on MMP-9-mediated invasion. • Unlike cantharidin, N-Benzylcantharidinamide has very low toxicity on Hep3B cells. • The reduced MMP-9 expression was due to HuR-mediated decrease of mRNA stability. • We suggest N-Benzylcantharidinamide as a novel inhibitor of MMP-9-related invasion. - Abstract: Invasion and metastasis are major causes of malignant tumor-associated mortality. The present study aimed to investigate the molecular events underlying inhibitory effect of N-Benzylcantharidinamide, a novel synthetic analog of cantharidin, on matrix metalloproteinase-9 (MMP-9)-mediated invasion in highly metastatic hepatocellular carcinoma Hep3B cells. In this investigation, among six analogs of cantharidin, only N-Benzylcantharidinamide has the inhibitory action on MMP-9 expression at non-toxic dose. The MMP-9 expression and invasion of Hep3B cells were significantly suppressed by treatment of N-Benzylcantharidinamide in a dose-dependent manner. On the other hand, the transcriptional activity of MMP-9 promoter and nuclear levels of NF-κB and AP-1 as the main transcriptional factors inducing MMP-9 expression were not affected by it although the level of MMP-9 mRNA was reduced by treatment of N-Benzylcantharidinamide. Interestingly, the stability of MMP-9 mRNA was significantly reduced by N-Benzylcantharidinamide-treatment. In addition, the cytosolic translocation of human antigen R (HuR), which results in the increase of MMP-9 mRNA stability through interaction of HuR with 3′-untranslated region of MMP-9 mRNA, was suppressed by treatment of N-Benzylcantharidinamide, in a dose-dependent manner. Taken together, it was demonstrated, for the first time, that N-Benzylcantharidinamide suppresses MMP-9 expression by reducing HuR-mediated MMP-9 mRNA stability for the inhibition of invasive potential in highly metastatic Hep3B cells.

  18. Late Progresses in Research of ECM1,MMP-9 and Gastric Cancer%ECM1、MMP-9与胃癌的研究新进展

    Institute of Scientific and Technical Information of China (English)

    李晓虹; 吴秋婉

    2011-01-01

    Extracellular matrix protein-1 ( ECM1 ) is a kind of secreted glycoprotein,which can promote endothelial cells proliferation and angiogenesis. ECM1 expression is significantly elevated in gastric cancer tissues and other malignant epithelial tumors, which gives rise to its potential correlation with tumor infiltration and metastasis. Matrix metalloproteinase-9( MMP-9 ) can degrade the basement membrane and the extracellular matrix, promote vascularization and enhance the invasiveness and metastasis of gastric cancer cells. Thus,to discuss the roles of ECM1 and MMP-9 in the carcinogenesis and development of gastric cancer will help further realize the interaction of cancer cells and their surrounding microenvironment, and provide theoretical basis for early diagnosis and treatment of gastric cancer.%细胞外基质蛋白-1(ECM1)是一种分泌型糖蛋白,可刺激内皮细胞增殖,促进血管形成.在胃癌组织和其他恶性上皮肿瘤中高表达,与恶性肿瘤的浸润和转移相关.基质金属蛋白酶9(MMP-9)可降解基底膜和细胞外基质,促进脉管形成而增强胃癌细胞的侵袭和转移能力.探讨ECM1与MMP-9在胃癌发生发展中的作用将有助于人们进一步认识肿瘤与其周围微环境相互作用的机制,为胃癌的早期诊断和治疗提供理论依据.

  19. Concurrent alterations of RAGE, RECK, and MMP9 protein expression are relevant to Epstein-Barr virus infection, metastasis, and survival in nasopharyngeal carcinoma.

    Science.gov (United States)

    Zhou, Dong-Ni; Deng, Yan-Fei; Li, Rong-Hua; Yin, Ping; Ye, Chun-Sheng

    2014-01-01

    This study aimed to concurrently investigate the expressions of receptor for advanced glycation end products (RAGE), reversion inducing cysteine-rich protein with Kazal motifs (RECK) and matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and their correlations with clinicopathological properties. Using immunohistochemistry, we found that RECK expression was downregulated in NPC tissues compared with chronic nasopharyngitis (CNT) tissues, while RAGE and MMP9 expressions were upregulated. We further found that RECK expression level was inversely correlated with MMP9 expression level in NPC, whereas RAGE expression level was positively correlated with MMP9 expression level. Moreover, aberrant expressions of these proteins had a positive correlation with the titers of EBVCA-IgA, lymphatic metastasis, recurrence and survival. Together, these findings suggest that dysregulations of RECK and RAGE expressions may be collectively involved in tumor progression of NPC by regulating MMP9 expression and that they may be a good prognostic predictors for NPC.

  20. Effect of human osteopontin on proliferation, transmigration and expression of MMP-2 and MMP-9 in osteosarcoma cells

    Institute of Scientific and Technical Information of China (English)

    刘思金; 胡国法; 刘亚军; 刘思国; 高虹; 张传生; 魏影允; 薛延; 劳为德

    2004-01-01

    Background To explore the effect of human osteopontin (hOPN) on the proliferation, transmigration and expression of matrix metallproteinase-2 (MMP-2) and matrix metallproteinase-9 (MMP-9) in osteosarcoma (OS) cells in vitro. Methods The prokaryotic-expression vector of hOPN was produced, hOPN was then subcloned into E. coli BL21 (DE3) cells and purified with ProBondTM Columns. The proliferation, cell cycle and the expression of cyclin A in OS cells were investigated by using MTT assay, flow cytometry and Western blot respectively. The transmigration of OS cells was checked by using transwell cell culture chamber. The micro-pore-filter-membrane system was used to study the chemiotaxis of hOPN to OS cells. The levels of total protein were examined according to Coomassie Brilliant Blue manuals. The expression of MMP-2 and MMP-9 were evaluated by detecting the volume of degradation of gelatin on SDS-PAGE gel.Results The prokaryotic-expression vector of hOPN and purified hOPN protein were achieved hOPN promoted OS cells proliferation in a dose-dependent manner, and stimulated cyclin A expression in OS cells to accelerate cell division cycle, hOPN facilitated the trans-membrane migration of OS cells. hOPN also enhanced the secretion of MMP-2 and MMP-9 in OS cells. Conclusion hOPN could stimulate cyclin A expression in OS cells, hOPN has chemiotaxis to OS cells and increases their transmigration, hOPN enhances the secretion of MMP-2 and MMP-9 in OS cells.

  1. MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation.

    LENUS (Irish Health Repository)

    Allott, Emma H

    2011-11-28

    Overweight and obesity is linked to increased incidence and mortality of many cancer types. Of all cancers, oesophageal adenocarcinoma (OAC) displays one of the strongest epidemiological links with obesity, accounting for up to 40% of cases, but molecular pathways driving this association remain largely unknown. This study aimed to elucidate mechanisms underpinning the association of obesity and cancer, and to determine if visceral obesity is associated with aggressive tumour biology in OAC. Following co-culture with visceral adipose tissue explants, expression of genes involved in tumour cell invasion and metastasis (matrix metalloproteinase (MMP)2 and MMP9) were upregulated between 10-fold (MMP2) and 5000-fold (MMP9), and expression of tumour suppressor p53 was downregulated 2-fold in OAC cell lines. Western blotting confirmed these results at the protein level, while zymographic analysis detected increased activity of MMPs in OAC cell lines following co-culture with adipose tissue explants. When OAC cell lines were cultured with adipose tissue conditioned media (ACM) from visceral adipose tissue, increased proliferative, migratory and invasive capacity of tumour cells was observed. In OAC patient tumour biopsies, elevated gene expression of MMP9 was associated with visceral obesity, measured by visceral fat area, while increased gene expression of MMP9 and decreased gene expression of tumour suppressor p53 was associated with poor tumour differentiation. These novel data highlight an important role for visceral obesity in upregulation of pro-tumour pathways contributing to aggressive tumour biology, and may ultimately lead to development of stratified treatment for viscerally obese OAC patients. © 2011 Wiley Periodicals, Inc.

  2. Serum IL-10, MMP-7, MMP-9 Levels in Helicobacter pylori Infection and Correlation with Degree of Gastritis

    OpenAIRE

    Gontar Siregar; Sahat Halim; Ricky Sitepu

    2016-01-01

    AIM: Helicobacter pylori causes gastric mucosal inflammation and immune reaction. However, the increase of IL-10, MMP-7, and MMP-7 levels in the serum is still controversial. The objective of this study was to investigate the serum levels of IL-10, MMP-7 & MMP-9 in gastritis patients with H. pylori infection. MATERIALS AND METHODS: A cross-sectional study was done on seventy gastritis patients that consecutive admitted to endoscopy units. The diagnosis of gastritis was made based on histo...

  3. Serum IL-10, MMP-7, MMP-9 Levels in Helicobacter pylori Infection and Correlation with Degree of Gastritis

    OpenAIRE

    Siregar, Gontar; Halim, Sahat; Sitepu, Ricky

    2016-01-01

    AIM: Helicobacter pylori causes gastric mucosal inflammation and immune reaction. However, the increase of IL-10, MMP-7, and MMP-7 levels in the serum is still controversial. The objective of this study was to investigate the serum levels of IL-10, MMP-7 & MMP-9 in gastritis patients with H. pylori infection.MATERIALS AND METHODS: A cross-sectional study was done on seventy gastritis patients that consecutive admitted to endoscopy units. The diagnosis of gastritis was made based on histopatho...

  4. Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells.

    Science.gov (United States)

    Pahne-Zeppenfeld, Jennifer; Schröer, Nadine; Walch-Rückheim, Barbara; Oldak, Monika; Gorter, Arko; Hegde, Subramanya; Smola, Sigrun

    2014-05-01

    Cervical carcinogenesis is a consequence of persistent infection with high-risk human papillomaviruses (HPVs). Recent studies indicate that HPV-transformed cells actively instruct their microenvironment to promote carcinogenesis. Here, we demonstrate that cervical cancer cells activate monocytes to produce their own CCL2 for further monocyte recruitment and reprogram their function during differentiation and maturation to dendritic cells (DCs). Our data show that cervical cancer cells suppress the induction of the chemokine receptor CCR7 in phenotypically mature DCs and impair their migration toward a lymph node homing chemokine, required to initiate adaptive immune responses. We confirmed the presence of CD83(+)CCR7(low) DCs in cancer biopsies. The second factor essential for DC migration, matrix-metalloproteinase MMP-9, which also has vasculogenic and protumorigenic properties, is not suppressed but upregulated in immature as well as mature DCs. We identified interleukin-6 (IL-6) as a crucial cervical cancer cell-derived mediator and nuclear factor kappaB (NF-jB) as the central signaling pathway targeted in DCs. Anti-IL-6 antibodies reverted not only NF-jB inhibition and restored CCR7-dependent migration but also blocked MMP-9 induction. This is the first report demonstrating the dissociation of CCR7 and MMP-9 expression in phenotypically mature CD83(+) DCs by cancer cells. Our results show that cervical cancer cells actively shape the local microenvironment. They induce the accumulation of myeloid cells and skew their function from immune activation to local production of protumorigenic MMP-9. Neutralizing anti-IL-6 antibodies can counteract this functional dysbalance and should therefore be considered for adjuvant cervical cancer therapy.

  5. Elevation of MMP-3 and MMP-9 in CSF and Blood in Patients with Severe Traumatic Brain Injury

    Science.gov (United States)

    Grossetete, Mark; Phelps, Jeremy; Arko, Leopold; Yonas, Howard; Rosenberg, Gary A.

    2009-01-01

    OBJECTIVE Traumatic brain injury (TBI) causes elevation of matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier (BBB) disruption, hemorrhage and cell death. We hypothesized that patients with TBI have an increase in MMPs in the ventricular cerebrospinal fluid (CSF) and plasma. METHODS Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement, and 24 and 72 hrs after admission. Seven TBI patients were entered into the study with six having complete data for analysis. Only patients that had a known time of insult that fell within a six hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus (NPH). Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblotting. RESULTS We found a significant elevation in the levels of the latent form of MMP-9 (92-kDa) in the CSF obtained at the time of arrival (TOA) (p<0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly elevated in the CSF, indicating endogenous MMP production. Western immunoblots showed increased levels of MMP-3 in CSF at all times measured, while MMP-3 was not detected in the CSF of NPH. CONCLUSIONS We show that MMPs are elevated in CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated elevations of MMP-3 and MMP-9 in ventricular CSF in TBI patients compared to controls. While these preliminary results will need to be replicated, we propose that MMPs may be important in BBB opening and hemorrhage secondary to brain injury in patients. PMID:19834375

  6. Stomach Cancer: Interconnection between the Redox State, Activity of MMP-2, MMP-9 and Stage of Tumor Growth.

    Science.gov (United States)

    Burlaka, Anatoly P; Ganusevich, Irina I; Gafurov, Marat R; Lukin, Sergey M; Sidorik, Evgeny P

    2016-04-01

    High levels of reactive oxygen (ROS) and nitrogen (RNS) species can lead to the destruction of extracellular matrix facilitating tumor progression. ROS can activate matrix metalloproteinases (MMP), damage DNA and RNA. Therefore, the levels of MMP, ROS and RNS can serve as additional prognostic markers and for the estimation of the effectiveness of tumor therapy. Concerning gastric cancer, the prognostic role of MMP, its connection with the cancer staging remains controversial and correlations between the activity of MMP with the ROS and RNS levels are insufficiently confirmed. Superoxide generation rates, nitric oxide (NO) levels, concentrations of active forms of matrix metalloproteinases MMP-2 and MMP-9 in tumor and adjacent tissues of patients with stomach cancer at different disease stages were measured by electron spin resonance (ESR) including spin-trapping and polyacrylamide gel zymography. It is shown that the activity of MMP-2 and MMP-9 in tumor tissue correlate with the superoxide radicals generation rate and NO levels (r = 0.48÷0.67, p < 0.05). The activity of MMP-2 and MMP-9 in tumor tissues and superoxide radical generation rates correlate positively with the stage of regional dissemination (r = 0.45 and 0.37, correspondingly, p < 0.05), but MMP-2 and MMP-9 activity inversely depends on distant metastatic degree of stomach cancer (r = 0.58; p < 0.05). Additionally, the feasibility of ESR to locally determine oxidative stress is demonstrated.

  7. Hematopoietic Stem Cell Mobilization and Homing after Transplantation: The Role of MMP-2, MMP-9, and MT1-MMP

    Directory of Open Access Journals (Sweden)

    Neeta Shirvaikar

    2012-01-01

    Full Text Available Hematopoietic stem/progenitor cells (HSPCs are used in clinical transplantation to restore hematopoietic function. Here we review the role of the soluble matrix metalloproteinases MMP-2 and MMP-9, and membrane type (MT1-MMP in modulating processes critical to successful transplantation of HSPC, such as mobilization and homing. Growth factors and cytokines which are employed as mobilizing agents upregulate MMP-2 and MMP-9. Recently we demonstrated that MT1-MMP enhances HSPC migration across reconstituted basement membrane, activates proMMP-2, and contributes to a highly proteolytic bone marrow microenvironment that facilitates egress of HSPC. On the other hand, we reported that molecules secreted during HSPC mobilization and collection, such as hyaluronic acid and thrombin, increase MT1-MMP expression in cord blood HSPC and enhance (prime their homing-related responses. We suggest that modulation of MMP-2, MMP-9, and MT1-MMP expression has potential for development of new therapies for more efficient mobilization, homing, and engraftment of HSPC, which could lead to improved transplantation outcomes.

  8. ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13

    Science.gov (United States)

    Zhao, Gexin; Yokoyama, Tadafumi; Huang, Yan; Bishop, Kevin; Maduro, Valerie; Accardi, John; Toro, Camilo; Boerkoel, Cornelius F.; Gahl, William A.; Duan, Xiaohong; Malicdan, May Christine V.; Lin, Shuo

    2017-01-01

    ATP6V1H is a component of a large protein complex with vacuolar ATPase (V-ATPase) activity. We identified two generations of individuals in which short stature and osteoporosis co-segregated with a mutation in ATP6V1H. Since V-ATPases are highly conserved between human and zebrafish, we generated loss-of-function mutants in atp6v1h in zebrafish through CRISPR/Cas9-mediated gene knockout. Homozygous mutant atp6v1h zebrafish exhibited a severe reduction in the number of mature calcified bone cells and a dramatic increase in the expression of mmp9 and mmp13. Heterozygous adults showed curved vertebra that lack calcified centrum structure and reduced bone mass and density. Treatment of mutant embryos with small molecule inhibitors of MMP9 and MMP13 significantly restored bone mass in the atp6v1h mutants. These studies have uncovered a new, ATP6V1H-mediated pathway that regulates bone formation, and defines a new mechanism of disease that leads to bone loss. We propose that MMP9/MMP13 could be therapeutic targets for patients with this rare genetic disease. PMID:28158191

  9. Largescale Transcriptomics Analysis Suggests Over-Expression of BGH3, MMP9 and PDIA3 in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    He, Yuan; Shao, Fangyang; Pi, Weidong; Shi, Cong; Chen, Yujia; Gong, Diping; Wang, Bingjie; Cao, Zhiwei; Tang, Kailin

    2016-01-01

    Oral squamous cell carcinoma (OSCC) has been reported as the most prevalent cancer of the head and neck region, while early diagnosis remains challenging. Here we took a comprehensive bioinformatics study on microarray data of 326 OSCC clinical samples with control of 165 normal tissues. The cell interaction pathways of ECM-receptor interaction and focal adhesion were found to be significantly regulated in OSCC samples. Further analysis of the topological properties and expression consistency identified that three hub genes in the gene interaction network, MMP9, PDIA3 and BGH3, were consistently up-expressed in OSCC samples. When being validated on additional microarray datasets of 41 OSCC samples, the validation rate of over-expressed BGH3, MMP9, and PDIA3 reached 90%, 90% and 84% respectively. At last, immuno-histochemical assays were done to test the protein expression of the three genes on newly collected clinical samples of 35 OSCC, 20 samples of pre-OSCC stage, and 12 normal oral mucosa specimens. Their protein expression levels were also found to progressively increase from normal mucosa to pre-OSCC stage and further to OSCC (ANOVA p = 0.000), suggesting their key roles in OSCC pathogenesis. Based on above solid validation, we propose BGH3, MMP9 and PDIA3 might be further explored as potential biomarkers to aid OSCC diagnosis.

  10. Largescale Transcriptomics Analysis Suggests Over-Expression of BGH3, MMP9 and PDIA3 in Oral Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yuan He

    Full Text Available Oral squamous cell carcinoma (OSCC has been reported as the most prevalent cancer of the head and neck region, while early diagnosis remains challenging. Here we took a comprehensive bioinformatics study on microarray data of 326 OSCC clinical samples with control of 165 normal tissues. The cell interaction pathways of ECM-receptor interaction and focal adhesion were found to be significantly regulated in OSCC samples. Further analysis of the topological properties and expression consistency identified that three hub genes in the gene interaction network, MMP9, PDIA3 and BGH3, were consistently up-expressed in OSCC samples. When being validated on additional microarray datasets of 41 OSCC samples, the validation rate of over-expressed BGH3, MMP9, and PDIA3 reached 90%, 90% and 84% respectively. At last, immuno-histochemical assays were done to test the protein expression of the three genes on newly collected clinical samples of 35 OSCC, 20 samples of pre-OSCC stage, and 12 normal oral mucosa specimens. Their protein expression levels were also found to progressively increase from normal mucosa to pre-OSCC stage and further to OSCC (ANOVA p = 0.000, suggesting their key roles in OSCC pathogenesis. Based on above solid validation, we propose BGH3, MMP9 and PDIA3 might be further explored as potential biomarkers to aid OSCC diagnosis.

  11. 罗格列酮对DM2患者血清MMP-9和TIMP-1影响的研究%The Effects of Rosiglitazone on the Serum MMP-9 and TIMP-1 in Type 2 Diabetic

    Institute of Scientific and Technical Information of China (English)

    倪强; 张健; 姚永良

    2012-01-01

    Objective To explore the change of rosiglitazone on type 2 diabetic patients and the impact on the expressions of MMP-9 and TIMP-1. Methods The clinical observation using randomized controlled method, 100 patients with DM2 were selected in our stud-y,and 50 healthy adults served as normal control. 100 cases of type 2 diabetics were divided into A and B group. The group A was treated only with conventional therapy. Tne group B was given rosiglitazone besides conventional therapy. And the concentrations of MMP-9 and TIMP-1 in serum were detected before and after therapy. Results Tne DM2 diabetics group serum MMP-9,TIMP-1 and MMP-9/TTMP-1 levels were obvious higher than the healthy control group(P0.05). There was a positive correlation be-tween MMP-9/TTMP-1 and expression level of MMP-9 and TTMP-1 in DM2 diabetics(r =0.631 ,r = 0.558,all P0.05);且MMP-9与TIMP-1之间,MMP-9/TIMP-1与MMP-9、TIMP-1之间均呈正相关.结论:血清MMP-9与TIMP-1可能与DM2发生、发展有关,罗格列酮能显著降低DM2患者MMP-9与TIMP-1水平,纠正MMP-9/TIMP-1比值,以期达到早期诊治,防止DM2大血管病变的目的.

  12. 急性脑梗死患者血清MMP-2、MMP-9和hs-CRP检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王清峰

    2010-01-01

    目的 检测急性脑梗死(ACI)患者血清中基质金属蛋白酶-2(MMP-2)、MMP-9和超敏C反应蛋白(hs-CRP)的表达,探讨其临床意义.方法 选取102例ACI患者作为观察组,40例健康查体者作为对照组,检测两组血清MMP-2、MMP-9和hs-CRP水平.结果 观察组MMP-2、MMP-9和hs-CRP表达显著高于对照组,且随梗死范围的增大而升高(P<0.05);观察组MMP-9与hs-CRP的表达呈正相关(r=0.402,P<0.05). 结论 MMP-2、MMP-9和hs-CRP在ACI的发生发展中可能起重要作用;MMP-9和hs-CRP可能具有协同作用,早期联合检测MMP-2、MMP-9和hs-CRP有助于判断脑梗死病变程度.

  13. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    Science.gov (United States)

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia.

  14. Prognostic value of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase N/CD13 in breast cancer patients.

    Science.gov (United States)

    Ranogajec, Irena; Jakić-Razumović, Jasminka; Puzović, Velibor; Gabrilovac, Jelka

    2012-06-01

    The aim of this study was to analyse the expression of matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase APN/CD13 in breast carcinoma samples, and their possible prognostic value in breast cancer patients. The expression of MMP-2, MMP-9 and APN/CD13 in tumor cells was analysed in 138 breast carcinomas by immunohistochemical staining of tumor cells using the semiquantitative method for the detection of cytoplasmic and membrane reaction in tumor cells as well as stromal cells positivity. MMP-2 was positive in tumor cells of 52.9% patients and in stromal cells of 74.6% patients, while MMP-9 positive tumor and stromal cells were found in 84.8 and 63.8% patients, respectively. Tumor cell APN/CD13 expression was found in 36.2% patients. Stromal cell MMP-2 expression correlated significantly with tumor size and neoangiogenesis. A positive correlation was also observed between tumor cell MMP-9 expression and hormone receptor status. Stromal cell coexpression of MMP-2/MMP-9 correlated significantly with tumor size. APN/CD13 expression in tumor cells significantly correlated with tumor type and neoangiogenesis. Overall survival was significantly shorter in patients with MMP-2, MMP-2/MMP-9 positive tumor cells, and tended to be shorter in patients with APN/CD13 positive tumor cells. Coexpression of MMP-2/MMP-9 in tumor cells was an independent risk factor for patient survival (OD = 13.9). Our results suggest that MMP-2, MMP-9, APN/CD13 expression and MMP-2/MMP-9 coexpression in combination with other standard prognostic factors can serve as a poor prognostic factor in the evaluation of breast cancer prognosis.

  15. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages

    Directory of Open Access Journals (Sweden)

    Qi-Ming Wang

    2016-11-01

    Full Text Available Background/Aims: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer and MMPs (matrix metalloproteinases by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA. Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. Results: We showed that EGCG (10-50µmol/L significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2, p38 and c-Jun N-terminal kinase (JNK in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Conclusion: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.

  16. 强力霉素对胃癌细胞增殖及Notch1、MMP-9表达的影响%Effect of Doxycycline on Gastric Cancer Cell Proliferation and Notch1, MMP-9 Expression

    Institute of Scientific and Technical Information of China (English)

    许敏; 李红

    2014-01-01

    Objective To investigate the effect of Doxycycline on gastric cancer cell line BGC-823 proliferation and Notch1, Matrix metalloproteinase-9(MMP-9)expression in order to shine a light on new anticancer drugs. Methods Final concentration of 0, 5, 10, 20, 40 mg/L doxycycline were added into human gastric cancer cell line BGC-823. Cell pro-liferation was detected by MTT;Cell cycle distribution was assessed by flow cytometry;Notch1, MMP-9 protein expression was revealed by Immunoblot. Results Doxycycline can inhibit proliferation of human gastric cancer cells line BGC-823, and its effect is dose and time-dependent(P<0.01). Doxycycline alters distribution of gastric cancer cell line BGC-823. With increasing drug concentration, the proportion of cells in S phase dropped(P<0.01). Notch1 expression rose and MMP-9 expression decreased(P<0.01). Conclusion Doxycyclinecan inhibited gastric cancer cell line BGC-823 prolif-eration and up-regulating Notch1 might be one mechanisms.%目的:研究强力霉素对胃癌细胞BGC-823细胞的增殖及Notch1、基质金属蛋白酶-9(MMP-9)蛋白表达的影响,为胃癌的治疗提供新的抗肿瘤药物。方法分别以0、5、10、20、40 mg/L终浓度的强力霉素作用于人胃癌细胞系BGC-823,运用MTT法检测细胞增殖程度;流式细胞仪检测细胞周期分布的影响;Western Blot检测Notch1、MMP-9蛋白水平的表达。结果强力霉素能够抑制人胃癌细胞BGC-823细胞的增殖,且有剂量及时间依赖性(P<0.01);强力霉素能够改变胃癌细胞BGC-823周期的分布,随着浓度的增加,S期所占比例降低;并且随着浓度的增加,Notch1的表达增强,MMP-9的表达降低(P<0.01)。结论强力霉素能够抑制胃癌细胞BGC-823的增殖,促进Notch1上调为可能的机制之一。

  17. Inhibitory effect of the carnosine-gallic acid synthetic peptide on MMP-2 and MMP-9 in human fibrosarcoma HT1080 cells.

    Science.gov (United States)

    Kim, Sung-Rae; Eom, Tae-Kil; Byun, Hee-Guk

    2014-09-01

    Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade extracellular matrix components and play important roles in a variety of biological and pathological processes such as malignant tumor metastasis and invasion. In this study, we constructed carnosine-gallic acid peptide (CGP) to identify a better MMP inhibitor than carnosine. The inhibitory effects of CGP on MMP-2 and MMP-9 were investigated in the human fibrosarcoma (HT1080) cell line. As a result, CGP significantly decreased MMP-2 and MMP-9 expression levels without a cytotoxic effect. Moreover, CGP may inhibit migration and invasion in HT1080 cells through the urokinase plasminogen activator (uPA)-uPA receptor signaling pathways to inhibit MMP-2 and MMP-9. Based on these results, it appears that CGP may play an important role in preventing and treating several MMP-2 and MMP-9-mediated health problems such as metastasis.

  18. 人参皂甙Rg3对乳腺癌细胞表达MMP-2和MMP-9的影响

    Institute of Scientific and Technical Information of China (English)

    李博; 杨威; 郑永晨; 杨艳秋

    2005-01-01

    目的研究人参皂甙Rg3对乳腺癌细胞(MCF-7细胞)分泌的基质金属蛋白酶(MMP-2,MMP-9)表达的影响.方法采用酶谱法测定了人参皂甙Rg3对乳腺癌细胞(MCF-7)细胞分泌基质金属蛋白酶(MMP-2,MMP-9)的影响.结果酶谱分析表明人参皂甙Rg3能减少MCF-7细胞分泌MMP-2,MMP-9(P<0.05).结论人参皂甙Rg3能抑制MMP-2和MMP-9的分泌.

  19. Bone mineral density, Bone mineral contents, MMP-8 and MMP-9 levels in Human Mandible and alveolar bone: Simulated microgravity

    Science.gov (United States)

    Rai, Balwant; Kaur, Jasdeep; Catalina, Maria

    Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. It has been reported that head-down tilt bed-rest studies mimic many of the observations seen in flights. There is no study on the correlation on effects of mandibular bone and alveolar bone loss in both sex in simulating microgravity. This study was designed to determine the Bone mineral density and GCF MMP-8 MMP-9 in normal healthy subject of both sexes in simulated microgravity condition of -6 head-down-tilt (HDT) bed rest. The subjects of this investigation were 10 male and 10 female volunteers participated in three weeks 6 HDT bed-rest exposure. The Bone density and bone mineral contents were measured by dual energy X-ray absorptiometry before and in simulated microgravity. The GCF MMP-8 MMP-8 were measured by Enzyme-linked immunosorbent assays (Human Quantikine MMP-8,-9 ELISA kit). The bone mineral density and bone mineral contents levels were significantly decreased in simulated microgravity condition in both genders, although insignificantly loss was higher in females as compared to males. MMP-8 MMP-9 levels were significantly increased in simulated microgravity as compared to normal condition although insignificantly higher in females as compared to males. Further study is required on large samples size including all factors effecting in simulated microgravity and microgravity. Keys words-Simulated microgravity condition, head-down-tilt, Bone loss, MMP-8, MMP-9, Bone density, Bone mineral contents.

  20. Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression.

    Science.gov (United States)

    Zeng, Rong; Huang, Jun-Peng; Li, Xu Feng; Xiong, Wei-Bin; Wu, Gang; Jiang, Zhao-Jing; Song, Shu-Jie; Li, Ji-Qiang; Zheng, Yan-Fang; Zhang, Ji-Ren

    2016-04-01

    EPB41L3 may play a role as a metastasis suppressor by supporting regular arrangements of actin stress fibres and alleviating the increase in cell motility associated with enhanced metastatic potential. Downregulation of epb41l3 has been observed in many cancers, but the role of this gene in esophageal squamous cell carcinoma (ESCC) remains unclear. Our study aimed to determine the effect of epb41l3 on ESCC cell migration and invasion. We investigated epb41l3 protein expression in tumour and non-tumour tissues by immunohistochemical staining. Expression in the non-neoplastic human esophageal cell line Het-1a and four ESCC cell lines - Kyse150, Kyse510, Kyse450 and Caes17 - was assessed by quantitative Polymerase Chain Reaction (qPCR) and Western blotting. Furthermore, an EPB41L3 overexpression plasmid and EPB41L3-specific small interfering RNA were used to upregulate EPB41L3 expression in Kyse150 cells and to downregulate EPB41L3 expression in Kyse450 cells, respectively. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The expression levels of p-AKT, matrix metalloproteinase (MMP)2 and MMP9 were evaluated. Expression of epb41l3 was significantly lower in tumour tissues than in non-tumour tissues and in ESCC cell lines compared with the Het-1a cell line. Kyse450 and Caes17 cells exhibited higher expression of epb41l3 than Kyse150 and Kyse510 cells. Overexpressing epb41l3 decreased Kyse150 cell migration and invasion, whereas EPB41L3-specific small interfering RNA silencing increased these functions in Kyse450 cells. Furthermore, overexpressing epb41l3 led to downregulation of MMP2 and MMP9 in Kyse150 and Kyse510 cells. Our findings reveal that EPB41L3 suppresses tumour cell invasion and inhibits MMP2 and MMP9 expression in ESCC cells.

  1. 大鼠骨骼肌缺血后MMP-9的变化与骨骼肌损伤和重塑的关系%The modification of MMP-9 in rat skeletal muscle ischemia and the relationship between MMP-9 and muscular injury and remolding

    Institute of Scientific and Technical Information of China (English)

    李国华; 刘德群; 刘会仁

    2012-01-01

    目的 建立单一骨骼肌部分缺血损害动物模型,并观察骨骼肌缺血后基质蛋白酶9(MMP-9)的表达与骨骼肌重塑的关系.方法 解剖组:解剖新鲜Wistar大鼠后肢20只20侧,进行血管灌注,观测肌肉血管及神经走行.实验组:Wistar大鼠40只,随机均分为5组,正常对照组(A组)不经缺血处理;缺血1 d组(B组);缺血3 d组(C组);缺血5 d组(D组);缺血7 d组(E组).观察肌纤维横截面和肌细胞坏死程度,测定腓肠肌肌肉重量、毛细血管密度,Western blot法检测MMP-9的表达.结果 大鼠小腿三头肌血供丰富,腓肠肌内侧头血管相对独立.与A组比较,B组肌纤维横切面直径无明显变化,C、D、E组显著减小.肌肉毛细血管密度呈时间依赖性,随时间延长肌肉毛细血管密度明显下降,后逐渐增加.与A组比较,B组肌肉重量无明显变化,C组明显减轻,D组重量显著增加,E组重量下降到A组水平.细胞因子MMP-9变化呈时间依赖性,其表达与毛细血管密度变化平行.骨骼肌缺血导致MMP-9水平下降,而修复时MMP-9升高.结论 大鼠小腿三头肌血供丰富,为腓肠肌缺血后损害的评价提供了解剖学基础.骨骼肌缺血后,肌纤维功能损伤呈时间依赖性加重,缺血一定时间后肌纤维逐渐修复.骨骼肌修复和新毛细血管生成有关.%Objective To observe the changes of matrix metalloproteinase-9 in early stage of skeletal muscle ischemia and to analyze its correlation with skeletal muscle injury and remodeling by creating a single skeletal muscle ischemia animal model with dissecting triceps surae of rats. Methods 60 Wistar rats were divided into anatomic group and experimental group. 20 sides of fresh hindlimbs of 20 Wistar rats in the anatomic group were dessected and vascular arterial perfusion were given, then the following items were observed: muscle shape, blood vessel, nerve shape, muscle fiber shape. The other 40 Wistar rats were divided into 5 groups ( n = 8

  2. Calmodulin kinase II-dependent transactivation of PDGF receptors mediates astrocytic MMP-9 expression and cell motility induced by lipoteichoic acid

    Directory of Open Access Journals (Sweden)

    Hsieh Hsi-Lung

    2010-11-01

    Full Text Available Abstract Background Lipoteichoic acid (LTA is a component of Gram-positive bacterial cell walls, which has been found to be elevated in cerebrospinal fluid of patients suffering from meningitis. Moreover, matrix metalloproteinases (MMPs, MMP-9 especially, have been observed in patients with brain inflammatory diseases and may contribute to brain disease pathology. However, the molecular mechanisms underlying LTA-induced MMP-9 expression in brain astrocytes remain unclear. Objective The goal of this study was to examine whether LTA-induced cell migration is mediated by calcium/calmodulin (CaM/CaM kinase II (CaMKII-dependent transactivation of the PDGFR pathway in rat brain astrocytes (RBA-1 cells. Methods Expression and activity of MMP-9 induced by LTA was evaluated by zymographic, western blotting, and RT-PCR analyses. MMP-9 regulatory signaling pathways were investigated by treatment with pharmacological inhibitors or using dominant negative mutants or short hairpin RNA (shRNA transfection, and chromatin immunoprecipitation (ChIP-PCR and promoter activity reporter assays. Finally, we determined the cell functional changes by cell migration assay. Results The data show that c-Jun/AP-1 mediates LTA-induced MMP-9 expression in RBA-1 cells. Next, we demonstrated that LTA induces MMP-9 expression via a calcium/CaM/CaMKII-dependent transactivation of PDGFR pathway. Transactivation of PDGFR led to activation of PI3K/Akt and JNK1/2 and then activated c-Jun/AP-1 signaling. Activated-c-Jun bound to the AP-1-binding site of the MMP-9 promoter, and thereby turned on transcription of MMP-9. Eventually, up-regulation of MMP-9 by LTA enhanced cell migration of astrocytes. Conclusions These results demonstrate that in RBA-1 cells, activation of c-Jun/AP-1 by a CaMKII-dependent PI3K/Akt-JNK activation mediated through transactivation of PDGFR is essential for up-regulation of MMP-9 and cell migration induced by LTA. Understanding the regulatory mechanisms

  3. Rac1/β-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9

    Directory of Open Access Journals (Sweden)

    Minghua Fan

    2016-03-01

    Full Text Available Background/Aims: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs. Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. Methods: We measured the activity of Rac1 and its downstream targets, β-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the β-catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and β-catenin on trophoblast invasion. Results: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the β-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down

  4. Concurrent alterations of RAGE, RECK, and MMP9 protein expression are relevant to Epstein-Barr virus infection, metastasis, and survival in nasopharyngeal carcinoma

    OpenAIRE

    2014-01-01

    This study aimed to concurrently investigate the expressions of receptor for advanced glycation end products (RAGE), reversion inducing cysteine-rich protein with Kazal motifs (RECK) and matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and their correlations with clinicopathological properties. Using immunohistochemistry, we found that RECK expression was downregulated in NPC tissues compared with chronic nasopharyngitis (CNT) tissues, while RAGE and MMP9 expressions were u...

  5. Evidence For A Macromolecular Complex In Poor Prognosis CLL That Contains CD38, CD49d, CD44 and MMP-9.

    OpenAIRE

    Buggins, Andrea Gail Sherman; Levi, Ana; Gohil, Satyen; Fishlock, Keith; Patten, Piers E.M.; Calle, Yolanda; Yallop, Deborah; Devereux, Stephen

    2011-01-01

    Abstract Progressive chronic lymphocytic leukaemia is characterised by the accumulation of neoplastic B-cells in the tissues and correlates with the expression of prognostic biomarkers such as CD38, CD49d and matrix metalloproteinase-9 (MMP9), which are involved in migration and tissue invasion. In this study we investigated the physical relationship between these molecules and demonstrate that CD38, CD49d, MMP9 and CD44 are physically associated in a supramolecular cell surface co...

  6. Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma

    Science.gov (United States)

    Cai, Jinquan; Sun, Ying; Wang, Guangzhi; Li, Yongli; Li, Ruiyan; Feng, Yan; Han, Bo; Li, Jianlong; Tian, Yu; Yi, Liye; Jiang, Chuanlu

    2016-01-01

    Background Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM. Method The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of MMP9 expression with tumor progression was explored in glioma specimens of all grades. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the association of MMP9 expression with survival and response to temozolomide. Results MMP9 was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that MMP9 expression is correlated with glioma grade (p<0.0001). Additionally, low expression of MMP9 was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032). Additionally, the GBM patients with low MMP9 expression benefited from temozolomide (TMZ) chemotherapy regardless of the MGMT methylation status. Conclusions Patients with primary GBMs with low MMP9 expression may have longer survival and may benefit from temozolomide chemotherapy. PMID:27022952

  7. IVIG inhibits TNF-α-induced MMP9 expression and activity in monocytes by suppressing NF-κB and P38 MAPK activation.

    Science.gov (United States)

    Zhou, Cuizhen; Huang, Min; Xie, Lijian; Shen, Jie; Xiao, Tingting; Wang, Renjian

    2015-01-01

    Matrix metalloproteinase-9 (MMP9) has been involved in inflammatory and pathologic processes of coronary artery lesions (CAL) in Kawasaki disease (KD). Intravenous immunoglobulin (IVIG), a traditional treatment for Kawasaki disease, could decrease the expressions of MMP9. The purpose of this study was to investigate the protective effect of IVIG in chemotactic migration of monocyte and the regulation of MMP9 induced by tumor necrosis factor-α (TNF-α) in U937s. Studies were carried out with real time polymerase chain reaction (RT-PCR), zymographic, Western blotting and immunofluorescence. U937s' migration was enhanced by TNF-α stimulation, while was inhibited by IVIG pretreatment. MMP9 expression and activity in U937s were also significantly enhanced by TNF-α and inhibited by IVIVG pretreatment. During inflammatory stimulus, nuclear factor kappa B (NF-κB) and P38 Mitogenactivated protein kinase (P38 MAPK) pathways play a significant role in regulating MMP9 gene expression. TNF-α induced nuclear translocation of NF-κB and P38 MAPK activation in U937s were inhibited significantly by IVIG. Furthermore, we clarified that nuclear NF-κB and P38 MAPK pathways play pivotal roles in regulating U937s' migration and MMP9 expressions using PDTC and SB203580, which were specific inhibitors of NF-κB and p38 MAPK pathways. IVIG displays striking biological effects, notably promoting monocyte migration. These effects involve the NF-κB and p38 pathways, and increased MMP9 activity. It might be a crucial mechanism of IVIG reducing the occurrence of CAL that IVIG inhibited monocytes expressing MMP9 and decreased chemotactic migration of monocyte.

  8. The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors

    DEFF Research Database (Denmark)

    Van den Steen, Philippe E; Van Aelst, Ilse; Hvidberg, Vibeke;

    2006-01-01

    with a compact three-dimensional structure. The OG and hemopexin domains have no influence on the cleavage efficiency of MMP-9 substrates. In contrast, the hemopexin domain contains a binding site for the cargo receptor low density lipoprotein receptor-related protein-1 (LRP-1). Furthermore, megalin/LRP-2...... domains down-regulate the bioavailability of active MMP-9 and the interactions with the cargo receptors are proposed to be the original function of hemopexin domains in MMPs....

  9. FSL-1 Induces MMP-9 Production through TLR-2 and NF-κB /AP-1 Signaling Pathways in Monocytic THP-1 Cells

    Directory of Open Access Journals (Sweden)

    Rasheed Ahmad

    2014-08-01

    Full Text Available Background: Matrix metalloproteinase-9 (MMP-9 is known to be implicated in the pathogenesis of many inflammatory disorders. FSL-1 (fibroblast-stimulating lipopeptide-1 induces cytokine production by monocytes/macrophages. However, it is unclear whether FSL-1 is also able to induce MMP-9 production. Herein, we determined whether FSL-1 could induce MMP-9 production, and if so, which signal transduction pathway(s were involved. Methods: MMP-9 expression was assessed with real-time qPCR and ELISA. Signaling pathways were studied by using THP1-XBlue™ cells, THP1-XBlue™-defMyD cells, anti-TLR2 mAb and pharmacological inhibitors. Phospho and total proteins were determined by Western blotting. Results: FSL-1 induces MMP-9 expression (PP-/- THP-1 cells did not express MMP-9 in response to FSL-1 treatment. By small interfering RNA-mediated knockdown, we also show that FSL-1-induced up-regulation of MMP-9 requires MyD88. Pre-treatment of THP-1 cells with inhibitors of JNK (SP600125, MEK/ERK (U0126; PD98056; XMD 8-92, p38 MAPK (SB203580 and NF-κB (BAY11-7085, Triptolide, Resveratrol significantly suppressed (PConclusion: These findings provide the first evidence that FSL-1 induces TLR-2-dependent MMP-9 gene expression which requires the recruitment of MyD88 and leads to activation of MEK1/2 /ERK 1/2, MEK5/ERK5, JNK, p38 MAPK and NF-κB/AP-1.

  10. The ERK1/2 Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina

    Directory of Open Access Journals (Sweden)

    Ghulam Mohammad

    2013-01-01

    Full Text Available This study was conducted to determine the expression of matrix metalloproteinase-9 (MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in a time-dependent manner and the effect of extracellular-signal-regulated kinases-1/2 (ERK1/2 inhibition on the expressions of MMP-9, TIMP-1, and inflammatory biomarkers in the retinas of diabetic rats. The expression of MMP-9 was quantified by zymography, and the mRNA level of MMP-9 and TIMP-1 was quantified by RT-PCR. The expression of inducible nitric oxide synthase (iNOS, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α was examined by Western blot analysis. MMP-9 expression was significantly higher in diabetic rat retinas compared to controls at all time points.TIMP-1 expression was nonsignificantly upregulated at 1week of diabetes and was significantly downregulated at 4 and 12 weeks of diabetes. Intravitreal administration of the ERK1/2 inhibitor U0126 prior to induction of diabetes decreased ERK1/2 activation, attenuated diabetes-induced upregulation of MMP-9, iNOS, IL-6, and TNF-α and upregulated TIMP-1 expression. In MMP-9 knockout mice, diabetes had no effect on retinal iNOS expression and its level remained unchanged. These data provide evidence that ERK1/2 signaling pathway is involved in MMP-9, iNOS, IL-6, and TNF-α induction in diabetic retinas and suggest that ERK1/2 can be a novel therapeutic target in diabetic retinopathy.

  11. Plasminogen activator inhibitor-1 controls bone marrow-derived cells therapeutic effect through MMP9 signaling: role in physiological and pathological wound healing.

    Science.gov (United States)

    Ebrahimian, Teni G; Squiban, Claire; Roque, Telma; Lugo-Martinez, Haydee; Hneino, Mohamad; Buard, Valerie; Gourmelon, Patrick; Benderitter, Marc; Milliat, Fabien; Tamarat, Radia

    2012-07-01

    We assessed the role of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase 9 (MMP9) in wound healing process and in the bone marrow mononuclear cells (BMMNC)-related effects on physiological and pathological wound healing. A full thickness excision wound was created by removal of the skin on the midback of irradiated and nonirradiated animals. Angiogenesis and re-epithelialization were markedly increased in PAI-1-/- mice compared to wild-type (WT) animals. We revealed high MMP activity in tissue of PAI-1-/- animals. Of interest, the wound healing process was reduced in PAI-1-/-:MMP9-/- animals compared to PAI-1-/- mice, suggesting a key role of MMP9 in beneficial effect of PAI-1 deficiency on wound closure. To unravel the role of PAI-1 in BMMNC relative effects, mice were treated with or without local injection of BMMNC isolated from WT, PAI-1-/-, and PAI-1-/-: MMP9-/- animals for 14 days (10(6) cells, n = 6 per group). In WT nonirradiated mice, transplantation of BMMNC isolated from PAI-1-/- animals enhanced wound formation when compared with WT BMMNC. BMMNC differentiation into cells with endothelial phenotype was enhanced by PAI-1 deficiency. These effects were abrogated in PAI-1-/-:MMP9-/- and MMP9-/- BMMNC. In addition, using chimeric mice, we demonstrated that PAI-1 deficiency environment increased the BMMNC-GFP recruitment to the wound site, whereas this effect was abrogated when using PAI-1-/-:MMP9-/- BMMNC. PAI-1 deficiency, at least through MMP9 upregulation, enhanced wound healing and BMMNC therapeutic potential in irradiated and nonirradiated animals.

  12. Brief discussion of the action of MMP-9 and TIMP-1 in pulmonary fibrosis%MMP-9和TIMP-1及其在肺纤维化中的作用

    Institute of Scientific and Technical Information of China (English)

    李芳

    2011-01-01

    肺纤维化是一类以弥漫性肺泡炎和肺泡结构紊乱并最终以瘢痕组织取代正常肺组织为特征的疾病.其发生包括早期的肺泡炎阶段和后期的肺纤维化阶段.肺纤维化的发病机理至今尚未清楚.近年来研究发现,基质金属蛋白酶(MMPS)及其抑制剂(TIMPS)与肺纤维化关系密切.本文就MMP-9和TIMP-1与肺纤维化的关系讲行了综述.%Pulmonary fibrosis encompasses a heterogeneous group of diseases characterized by diffuse alveolar inflam-mation , disruption of alveolar structures, and ultimately replacement of the lung parenchyma with scar tissue. This group of diseases features an early stage of alveolar inflammation and late stage of pulmonary fibrosis. The precise mechanisms of pulmonary fibrosis are poorly understood. Previous research has indicated that matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are closely associated with the development of pulmonary fibrosis. This paper reviews the rela-tionship between MMP-9, TIMP-1 , and pulmonary fibrosis.

  13. 血清MMP-2、MMP-9水平与非小细胞肺癌转移关系的研究%Correlation of serum total MMP-2,MMP-9 levels with human non-small cell lung cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    雷建灵; 赵全年; 刘利; 高德荣

    2010-01-01

    目的 探讨非小细胞肺癌(NSCLC)患者血清MMP-2、MMP-9水平与非小细胞肺癌的关系.方法 采用ELISA法检测70例非小细胞肺癌患者及26例健康志愿者血清MMP-2和MMP-9水平.结果 NSCLC患者血清MMP-2和MMP-9含量显著高于正常对照组.NSCLC有转移组血清MMP-2和MMP-9水平显著高于 NSCLC无转移组.结论 血清MMP-2和MMP-9的水平可作为预测非小细胞肺癌转移的指标.

  14. Gene Expression Analysis of an EGFR Indirectly Related Pathway Identified PTEN and MMP9 as Reliable Diagnostic Markers for Human Glial Tumor Specimens

    Directory of Open Access Journals (Sweden)

    Sergio Comincini

    2009-01-01

    Full Text Available In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found between PTEN and MMP9 mRNA levels. To verify if this correlation was conserved in gliomas, PTEN and MMP9 expression was further investigated in an additional panel of 16 anaplastic astrocytoma specimens and, in parallel, in different human normal and astrocytic tumor cell lines. In anaplastic astrocytomas PTEN expression was significantly higher than in glioblastoma multiforme, but no significant correlation was found between PTEN and MMP9 expression. PTEN and MMP9 mRNA levels were also employed to identify subgroups of specimens within the different glioma malignancy grades and to define a gene expression-based diagnostic classification scheme. In conclusion, this gene expression survey highlighted that the combined measurement of PTEN and MMP9 transcripts might represent a novel reliable tool for the differential diagnosis of high-grade gliomas, and it also suggested a functional link involving these genes in glial tumors.

  15. 脑室出血早产儿血浆MMP-2和MMP-9测定的临床意义%Significance of detection of plasma MMP-2 and MMP-9 in diagnosis of the periventricular hemorrhage intraventricular hemorrhage premature infants

    Institute of Scientific and Technical Information of China (English)

    江明荣; 黄循斌; 谢晓彬; 周曙明

    2012-01-01

    Objective To investigate the clinical significance of detection of plasma MMP-2 and MMP-9 in dangosis of the periventricular hemorrhage-intraventricular hemorrhage (PVH-IVH) premature infants. Methods ELISA method was to determine the contents of MMP-2 and MMP-9 in blood plasma of 40 premature infants and 20 controls premature infants without the complication of intracranial hemorrhage,etc. Results The contents of MMP-2 and MMP-9 in premature infants with PVH-IVH was significantly higher than those of the control group (P < 0.01 )and the contents of MMP-2 and MMP-9 increaed ohviously with the bleeding degree aggravation. Conclusion The change of contents of MMP-2 and MMP-9 in blood plasma disclose tge early occurrence and injury extent of PVH-IVH.%目的 探讨血浆基质金属蛋白酶-2和9(MMP-2、MMP-9)在早产儿脑室周围-脑室内出血(PVH-IVH)时的临床意义.方法 采用ELISA法测定早产儿脑室周围-脑室内出血患儿及20例对照组早产儿(无颅内出血等并发症)血浆MMP-2、MMP-9含量.结果 PVH-IVH患儿MMP-2、MMP-9比对照组早产儿显著升高(均P<0.01),随着出血程度加重,血浆MMP-2、MMP-9均明显升高(均P<0.01).结论 血浆MMP-2和MMP-9含量的变化,可客观早期的判断PVH-IVH的发生、损伤程度.

  16. BRD4 Phosphorylation Regulates HPV E2-Mediated Viral Transcription, Origin Replication, and Cellular MMP-9 Expression

    Directory of Open Access Journals (Sweden)

    Shwu-Yuan Wu

    2016-08-01

    Full Text Available Post-translational modification can modulate protein conformation and alter binding partner recruitment within gene regulatory regions. Here, we report that bromodomain-containing protein 4 (BRD4, a transcription co-factor and chromatin regulator, uses a phosphorylation-induced switch mechanism to recruit E2 protein encoded by cancer-associated human papillomavirus (HPV to viral early gene and cellular matrix metalloproteinase-9 (MMP-9 promoters. Enhanced MMP-9 expression, induced upon keratinocyte differentiation, occurs via BRD4-dependent recruitment of active AP-1 and NF-κB to their target sequences. This is triggered by replacement of AP-1 family members JunB and JunD by c-Jun and by re-localization of NF-κB from the cytoplasm to the nucleus. In addition, BRD4 phosphorylation is critical for E2- and origin-dependent HPV DNA replication. A class of phospho-BRD4-targeting compounds, distinct from the BET bromodomain inhibitors, effectively blocks BRD4 phosphorylation-specific functions in transcription and factor recruitment.

  17. Anti-inflammatory activities of Physalis alkekengi var. franchetii extract through the inhibition of MMP-9 and AP-1 activation.

    Science.gov (United States)

    Hong, Ju-Mi; Kwon, Ok-Kyoung; Shin, In-Sik; Song, Hyuck-Hwan; Shin, Na-Rae; Jeon, Chan-Mi; Oh, Sei-Ryang; Han, Sang-Bae; Ahn, Kyung-Seop

    2015-01-01

    Physalis alkekengi has been traditionally used for the treatment of coughs, middle ear infections, and sore throats in Korea, Europe, and China. It exhibits a variety of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-cancer effects. The anti-inflammatory effects of the P. alkekengi methanol extract (PA) and its molecular mechanisms have not yet been fully investigated. In the present study, the chromatogram of PA was established by UPLC analysis. The anti-inflammatory effects of PA were also investigated using murine microphage cell lines, RAW 264.7 cells, and a murine model of OVA induced asthma. In LPS-stimulated RAW264.7 cells, PA reduced the MMP-9 expression with decreases in the production of nitric oxide, inteleukin-6, and tumor necrosis factor-α. Furthermore, PA suppressed the phosphorylation of MAPKs, which resulted in the inhibition of AP-1 activation. These effects of PA were consistent with the results of the in vivo experiment. PA-treated mice significantly inhibited inflammatory cell counts and cytokine production in bronchoalveolar lavage fluids and airway-hyperresponsiveness in OVA-induced asthmatic mice. PA treated mice also showed a marked inhibition of inducible nitric oxide synthase and MMP-9 expression. In conclusion, our results suggest that PA may be a valuable therapeutic material in treating various inflammatory diseases, including allergic asthma.

  18. Effects of Etch-and-Rinse and Self-etch Adhesives on Dentin MMP-2 and MMP-9

    Science.gov (United States)

    Mazzoni, A.; Scaffa, P.; Carrilho, M.; Tjäderhane, L.; Di Lenarda, R.; Polimeni, A.; Tezvergil-Mutluay, A.; Tay, F.R.; Pashley, D.H.; Breschi, L.

    2013-01-01

    Auto-degradation of collagen matrices occurs within hybrid layers created by contemporary dentin bonding systems, by the slow action of host-derived matrix metalloproteinases (MMPs). This study tested the null hypothesis that there are no differences in the activities of MMP-2 and -9 after treatment with different etch-and-rinse or self-etch adhesives. Tested adhesives were: Adper Scotchbond 1XT (3M ESPE), PQ1 (Ultradent), Peak LC (Ultradent), Optibond Solo Plus (Kerr), Prime&Bond NT (Dentsply) (all 2-step etch-and-rinse adhesives), and Adper Easy Bond (3M ESPE), Tri-S (Kuraray), and Xeno-V (Dentsply) (1-step self-etch adhesives). MMP-2 and -9 activities were quantified in adhesive-treated dentin powder by means of an activity assay and gelatin zymography. MMP-2 and MMP-9 activities were found after treatment with all of the simplified etch-and-rinse and self-etch adhesives; however, the activation was adhesive-dependent. It is concluded that all two-step etch-and-rinse and the one-step self-etch adhesives tested can activate endogenous MMP-2 and MMP-9 in human dentin. These results support the role of endogenous MMPs in the degradation of hybrid layers created by these adhesives. PMID:23128110

  19. Autism phenotypes in ZnT3 null mice: Involvement of zinc dyshomeostasis, MMP-9 activation and BDNF upregulation.

    Science.gov (United States)

    Yoo, Min Heui; Kim, Tae-Youn; Yoon, Young Hee; Koh, Jae-Young

    2016-06-29

    To investigate the role of synaptic zinc in the ASD pathogenesis, we examined zinc transporter 3 (ZnT3) null mice. At 4-5 weeks of age, male but not female ZnT3 null mice exhibited autistic-like behaviors. Cortical volume and neurite density were significantly greater in male ZnT3 null mice than in WT mice. In male ZnT3 null mice, consistent with enhanced neurotrophic stimuli, the level of BDNF as well as activity of MMP-9 was increased. Consistent with known roles for MMPs in BDNF upregulation, 2.5-week treatment with minocycline, an MMP inhibitor, significantly attenuated BDNF levels as well as megalencephaly and autistic-like behaviors. Although the ZnT3 null state removed synaptic zinc, it rather increased free zinc in the cytosol of brain cells, which appeared to increase MMP-9 activity and BDNF levels. The present results suggest that zinc dyshomeostasis during the critical period of brain development may be a possible contributing mechanism for ASD.

  20. Morphology and MMP-9, AR and IGFR-1 responses of the seminal vesicle in TRAMP mice model.

    Science.gov (United States)

    Dal Pozzo, Caroline Fernanda Sanches; Kido, Larissa Akemi; Montico, Fabio; Gonçalves, Mariana Piccoli; Cagnon, Valéria Helena Alves

    2016-06-01

    Seminal vesicles are important hormone-dependent accessory sex glands. Transgenic adenocarcinoma of the mouse prostate (TRAMP) model has been used to evaluate malignant diseases in the prostate and in other sexual glands. The aim of this study was to characterize structural and molecular features of the seminal vesicle in different life periods of the TRAMP mice. Groups: Control Group (5 FVB/12 week old mice), TRAMP 12 and 22 Groups (10 TRAMP 12 and 22 week old mice, respectively). Seminal vesicles were evaluated by morphological and immunohistochemical parameters; androgenic receptor (AR), Insulin-like growth factor 1 (IGFR-1) and metalloproteinase 9 (MMP-9). The TRAMP mice showed frequent epithelial proliferation, including cellular stromal invasion, especially in the TRAMP 22 group. Intense AR reactivity was seen in both stroma and epithelial regions in the TRAMP 22 group. Intense IGFR-1 and MMP-9 stromal immunolabeling was identified in both TRAMP groups. Thus, there were structural and molecular changes in the seminal vesicle in TRAMP mice, compromising not only the structure but also the stromal signaling, damaging thus the function and leading to glandular lesions. TRAMP mice could be indicated as a good model to study alterations of the seminal vesicle in association to prostate cancer.

  1. RNA interference targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells by downregulating MMP-9.

    Science.gov (United States)

    Fan, Xiaobin; Wu, Weiguang; Shi, Haixia; Han, Jianqiu

    2013-07-01

    Cervical squamous carcinoma is a highly invasive tumour that has a great capacity to metastasise. Extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin superfamily, is a widely distributed cell surface glycoprotein. It is highly expressed on malignant tumour cell surfaces, including human cervical squamous carcinoma. It also plays a critical role in the invasive and metastatic activity of malignant cells by stimulating the expression of matrix metalloproteinases (MMPs). The anti-invasive effect of small interfering RNA (siRNA) against CD147 on human cervical squamous carcinoma cells and its possible pathways has been investigated. The downregulation of CD147 by transfection with siRNA resulted in MMP-9 expression and decreased activity in the cervical squamous carcinoma cell line SiHa. In vitro analysis showed that the invasive capacity of SiHa cells decreased. Thus CD147 inhibition and subsequent MMP-9 deletion may have anti-tumour effects by inhibiting the invasiveness of human cervical squamous carcinoma cells.

  2. Serum levels of matrix metalloproteinases MMP-2 and MMP-9 and their tissue natural inhibitors in breast tumors.

    Science.gov (United States)

    Jinga, D; Stefanescu, Maria; Blidaru, A; Condrea, Ileana; Pistol, Gina; Matache, Cristiana

    2004-01-01

    In this study, the levels of matrix metalloproteinases MMP-2 and MMP-9 were simultaneously analyzed with the levels of their tissue natural inhibitors TIMP-1 and TIMP-2 in sera of patients with breast tumors. At the same time, the activity of these two matrix metalloproteinases was evaluated. The decrease of TIMP-2 level in sera from patients with breast cancer as well as an imbalance between MMP-2 and TIMP-2 in neoplasic processes were found. The serum levels of MMP-2, MMP-9 and TIMP-1 were comparable between the patients with breast cancer and benign tumors. These experimental studied parameters were found to correlate with some of clinicopathological disease variables (TNM or pTNM staging system, tumor size and node invasion) suggesting their potential value for diagnosis and prognosis of breast cancer. Matrix metalloproteinases or their natural inhibitors and tumor markers (CA15.3 and CEA) not correlated between but, each of them correlated with another clinicopathological disease variable, suggesting their usefulness in the evaluation.

  3. Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF

    Directory of Open Access Journals (Sweden)

    Meacham Randall B

    2010-06-01

    Full Text Available Abstract Background Prostate-derived Ets factor (PDEF is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF in prostate cancer. Results We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression

  4. 支原体脂肽经EGFR/MMP-9诱导气道上皮细胞分泌MUC5AC

    Institute of Scientific and Technical Information of China (English)

    文道林; 余敏君; 游晓星; 李冉辉; 陈列松; 朱翠明; 李媛媛; 曾焱华

    2015-01-01

    目的:观察支原体巨噬细胞活化脂肽-2(MALP-2)诱导人气道上皮细胞分泌粘蛋白MUC5AC的分子机制。方法体外培养人气道上皮细胞NCI-H292,分别采用0、0.1、1.0和5.0μg/mL MALP-2刺激NCI-H292细胞24h,采用酶联免疫吸附测定(ELISA)检测培养上清中MUC5AC和基质金属蛋白酶9(MMP-9)的含量;Western blot检测表皮生长因子受体(EGFR)磷酸化水平。同时采用EGFR抑制剂AG-1478或MMP-9抑制剂(MMP-9 Inhibitor I)处理细胞,观察其对MUC5AC分泌的影响。结果 NCI-H292细胞未刺激时,MUC5AC以及MMP-9分泌水平极低。当给予0.1~5μg/mL MALP-2作用18h后,MUC5AC的分泌水平显著增高。此外,5μg/mL MALP-2作用NCI-H292细胞1h后可诱导EGFR磷酸化。采用AG-1478预处理细胞1h后,MMP-9及MUC5AC分泌水平明显减少,同时,采用10nmol/L MMP-9抑制剂处理后也能下调MUC5AC水平。结论支原体MALP-2经EGFR/MMP-9诱导气道上皮细胞分泌MUC5AC。%Objective To investigate the molecular mechanism of the Macrophage-activating lipopeptide-2 (MALP-2) on secretion of MUC5AC in human airway epithelial cells.Methods The airway epithelial cell line NCI-H292 was cultured in vitro and stimulated with 0, 0.1,1.0 and 5.0μg/mL of MALP-2 for 24h. Secretion of MUC5AC and matrix metalloprotein-9 (MMP-9) in the supernatant were detected by ELISA; Phosphorylation of epithelial growth factor receptor (EGFR) was measured by Western blot. To observe the effect of EGFR and MMP-9 on the mediation of MUC5AC secretion, specific inhibitor AG-1478 and MMP-9 Inhibitor I was used before MALP-2 stimulation.Results The secretion level of MUC5AC and MMP-9 was very low in untreated cells. 0.1-5μg/mL of MALP-2 incubation for 18h signifi cantly upregulated MUC5AC secretion. In addition, 5μg/mL MALP-2 could induce EGFR phosphorylation after 1h of incubation. Treatment of AG-1478, an inhibitor of EGFR, signifi cantly abrogated MALP-2-induced MMP-9 and

  5. Effect of Azadirachta indica (Neem) and Aloe vera as compared to subantimicrobial dose doxycycline on matrix metalloproteinases (MMP)-2 and MMP-9: An in-vitro study.

    Science.gov (United States)

    Kudalkar, Mithun D; Nayak, Aarati; Bhat, Kishore S; Nayak, Ranganath N

    2014-01-01

    A critical outcome of periodontal diseases is degradation of collagen in the periodontal tissues, by enzymes such as Matrix Metallo-Proteinases (MMPs). Doxycycline is known to down-regulate the activity of MMPs. Azadirachta indica (Neem) and Aloe vera are herbs known to have an anti-inflammatory effect. The present study was designed to evaluate the anti-inflammatory effect of Neem and Aloe vera by way of its inhibitory effect on MMP-2 and MMP-9 activity in cases of chronic periodontitis and compare it with doxcycline. A total of 30 subjects were enrolled in this study. Gingival tissue samples were obtained from patients diagnosed with the chronic periodontitis. The tissue extracts were treated with the said drug solutions and inhibition of MMP-2 and MMP-9 was analyzed. Enzymatic activity was detected by electrophoresis. The data was subjected to Student's paired t-test. The results showed that the activity of MMP-2 and MMP-9 was significantly decreased by the use of doxycycline, Neem and Aloe vera. A 53.5% reduction in the MMP-2 and 52.5% reduction in the MMP-9 activity was seen when samples were subjected to Neem treatment at the concentration of 1500 μg/ml. Tissues treated with Aloe vera in the concentration of 2000 μg/ml showed a 20.09% reduction in the MMP-2 and 20.4% reduction in the MMP-9 activity. Doxycycline in the concentration of 300 μg/ml, showed an 82.1% reduction in the MMP-2 and 82.6% reduction in the MMP-9 activity. The present study demonstrated an inhibitory effect of Neem and Aloe vera on MMP-2 and MMP-9, which are involved in the extracellular matrix degradation during periodontitis.

  6. In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines, inducers and inhibitors.

    Science.gov (United States)

    Roomi, M W; Monterrey, J C; Kalinovsky, T; Rath, M; Niedzwiecki, A

    2010-03-01

    Matrix metalloproteinases (MMPs) secreted by cervical and ovarian cancer, especially MMP-2 and MMP-9, play crucial roles in tumor invasion and metastasis. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 expression in cervical and ovarian cancer cell lines. Human cervical (HeLa and DoTc2-4510) and ovarian (SK-OV-3) cell lines were cultured in appropriate media. At near confluence, the cells were washed with PBS and incubated in serum-free medium with various concentrations of several cytokines, mitogens and inhibitors. After 24 h the media were removed and analyzed for MMP-2 and MMP-9 by gelatinase zymography and quantitated by densitometry. HeLa and SK-OV-3 cell lines expressed MMP-2 whereas DoTc2-4510 cells expressed MMP-9. Treatment of cervical cancer cell lines (HeLa and DoTc2-4510) with PMA had no effect on MMP-2 expression and a moderate stimulatory effect in ovarian cancer cell line SK-OV-3. MMP-9 was stimulated by phorbol 12-myristate 13-acetate in HeLa cells and enhanced in DoTc2-4510. Tumor necrosis factor-alpha and interleukin-1beta, had slight inhibitory effect on HeLa cell expression of MMP-2 while lipopolysaccharide stimulated MMP-2 in HeLa cells. Doxycycline, epigallocatechin gallate, a nutrient mixture, actinomycin-D, cyclohexamide, retinoic acid and dexamethasone inhibited MMP-2 in HeLa and SK-OV-3 cell lines and inhibited MMP-9 in DoTc2-4510. Our results show that cytokines, mitogens, inducers and inhibitors have an up or down regulatory effect on MMP-2 and MMP-9 expression in ovarian and cervical cancer cell lines, suggesting these agents may be effective strategies to treat these cancers.

  7. Plasma Levels of Matrix Metalloproteinase (MMP)-2, MMP-9 and Tumor Necrosis Factor-α in Chronic Hepatitis C Virus Patients

    Science.gov (United States)

    Abdel-Latif, Mohamed S

    2015-01-01

    Background: In chronic HCV infection, pathological accumulation of the extracellular matrix is the main feature of liver fibrosis; that indicates the imbalanced rate of increased matrix synthesis to decreased breakdown of connective tissue proteins. Matrix metalloproteinases (MMPs) play a crucial role in remodeling of extracellular matrix. It is known that expression of MMPs is regulated by Tumor necrosis factor (TNF)-α. Also, levels of TNF-α in liver and serum are increased in chronic HCV patient. Accordingly, this study aimed to correlate the plasma levels of MMP-2, MMP-9 and TNF-α in chronic HCV patients with the pathogenesis of the liver. Methods: The current study was conducted on 15 fibrotic liver cases with detectable HCV RNA, 10 HCV cirrhotic liver cases, and 15 control subjects of matched age and sex. Plasma MMP-2, MMP-9 and TNF-α were measured by ELISA. Results: Data revealed that the MMP2, MMP9 and TNF-α levels showed a significant elevation in chronic HCV patients compared to control group (p= 0.001). But, no significant correlation was observed in levels of MMP-2, MMP-9, and TNF-α between fibrotic and cirrhotic cases. Conclusions: MMP-2, MMP-9 and TNF-α showed high reproducibility to differentiate chronic HCV patients from control group. On the contrary, MMP-2, MMP-9 and TNF-α were not able to differentiate fibrotic from cirrhotic liver cases. Thus, MMP-2, MMP-9 and TNF-α could not be correlated with the progression of liver disease. Rather they could be used as prognostic markers of liver fibrosis. PMID:26464613

  8. Matrix metalloproteinase (MMP-9 in cancer-associated fibroblasts (CAFs is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Ayumi Taguchi

    Full Text Available Cancer associated fibroblasts (CAFs are responsible for tumor growth, angiogenesis, invasion, and metastasis. Matrix metalloproteinase (MMP-9 secreted from cancer stroma populated by CAFs is a prerequisite for cancer angiogenesis and metastasis. Omega-3 polyunsaturated fatty acids (omega-3 PUFA have been reported to have anti-tumor effects on diverse types of malignancies. Fat-1 mice, which can convert omega-6 to omega-3 PUFA independent of diet, are useful to investigate the functions of endogenous omega-3 PUFA. To examine the effect of omega-3 PUFA on tumorigenesis, TC-1 cells, a murine epithelial cell line immortalized by human papillomavirus (HPV oncogenes, were injected subcutaneously into fat-1 or wild type mice. Tumor growth and angiogenesis of the TC-1 tumor were significantly suppressed in fat-1 compared to wild type mice. cDNA microarray of the tumors derived from fat-1 and wild type mice revealed that MMP-9 is downregulated in fat-1 mice. Immunohistochemical study demonstrated immunoreactivity for MMP-9 in the tumor stromal fibroblasts was diffusely positive in wild type whereas focal in fat-1 mice. MMP-9 was expressed in primary cultured fibroblasts isolated from fat-1 and wild type mice but was not expressed in TC-1 cells. Co-culture of fibroblasts with TC-1 cells enhanced the expression and the proteinase activity of MMP-9, although the protease activity of MMP-9 in fat-1-derived fibroblasts was lower than that in wild type fibroblasts. Our data suggests that omega-3 PUFAs suppress MMP-9 induction and tumor angiogenesis. These findings may provide insight into mechanisms by which omega-3 PUFAs exert anti-tumor effects by modulating tumor microenvironment.

  9. Effects of high glucose on the expression of MMP-9 and TIMP-1 in primary cultured human mesangial cells%高糖对原代培养人肾小球系膜细胞表达MMP-9、TIMP-1的影响

    Institute of Scientific and Technical Information of China (English)

    尹燕志; 牟授菡; 鞠建伟; 吕丛奎; 孙晓燕; 邓磊修

    2011-01-01

    目的 了解高糖对原代培养的人肾小球系膜细胞表达MMP-9、TIMP-1 和 MMP-9/TIMP-1的影响,进一步探讨糖尿病肾病的发病机制.方法 取自愿水囊引产的胎儿肾,解剖取肾皮质剪碎,应用肾皮质组织块法合优生选择法对人肾小球系膜细胞进行原代培养.ELISA方法检测MMP-9、TIMP-1的表达变化.结果 与正常组相比较,高糖组MMP-9在24h、48h、72h均显著降低(P<0.01),TIMP-1在24h、72h可显著升高 (P<0.05),48h表达降低;MMP-9/TIMP-1的比值在24h、48h、72h均显著降低(P<0.01).结论 高糖能够降低MMP-9/TIMP-1,与肾小球系膜细胞细胞外基质降解能力降低密切相关.%Objective To observe the effect of high glucose on the expression of MMP-9 ,TIMP-1 and the ratio of MMP-9/TIMP-1 in primary cultured human mesangial cells, and to elucidate their possible roles in diabetic nephropathy. Methods Kidneys isolated from voluntary induced of labor with water bag were cut into pieces, and human mesangial cells were cultured with the method of renal cortical tissue combined with eugenic selection. Then ELISA was used to measure the expression of MMP-9 and TIMP-1, Results Compared with that of the normal group, the expression of MMP-9 in the high glucose group was significantly lower at 24h, 48h and 72h(P<0. 01) ;TIMP-lwas higher at 24h and 72h and lower at 48h (P < 0. 05); but the ratio of MMP-9/TIMP-1 was decreased constantly at 24h, 48h and 72h (P<0. 01). Conclusion High glucose decreases the ratio of MMP-9/TIMP-1 in mesangial cells in vitro , which may contribute to the inhibition of ECM degradation in glomerulus.

  10. TGF-beta1 Transgenic Mouse Model of Thoracic Irradiation: Modulation of MMP-2 and MMP-9 in the Lung Tissue

    Institute of Scientific and Technical Information of China (English)

    YANG Kunyu; Liu LI; ZHANG Tao; WU Gang; Ruebe Claudia; Ruebe Christian; HU Yu

    2006-01-01

    To investigate the effects of TGF-β1 on the two gelatinases (MMP-2 and MMP-9), and their roles in lung remodeling after irradiation-induced lung injury. Expressions of TGF-β1 were measured with western blot, and expressions of MMP-2 and MMP-9 were analyzed with zymography in a TGF-β1 transgenic mouse model after thoracic irradiation with 12 Gy. We found expressions of TGF-β1 in the lung from the transgenic mice were three folds as compared to those from control mice. With densitometrical analysis, we found a significant decrease in MMP-9 activity in lung homogenates from the transgenic mice as compared with those from non-transgenic control mice 8 weeks after sham-irradiation (relative MMP-9 activity: C: 1.000±0.1091; TG: 0.4772± 0.470 (n=8, P<0.05). But MMP-2 was constitutively expressed in the lung homogenates from the transgenic mice as compared to those from control mice 8 weeks aftersham-irradiation (relative MMP-2 activity 8 weeks after sham-irradiation: C: 1.000±0.1556, TG: 1.0075±0.1472). Eight weeks after thoracic irradiation with 12 Gy, we observed a significant increase of MMP-2 and MMP-9 activity in lung homogenates from both transgenic and normal mice. In TGF-β1 transgenic mice relative MMP-9 activity was increased to 1.5321±0. 2217 folds 8 weeks after thoracic irradiation with 12 Gy as compared to those after sham-irradiation (1.000±0.2153), and relative MMP-2 activity was increased to 1. 7142±0. 4231 folds. Our results show that TGF-β1 itself down-regulates activity of MMP-9, thereby decreases ECM degradation in lungs of TGF-β1 transgenic mice.Also we find that ionizing irradiation upregulates both MMP-2 and MMP-9 activity. Over-expressions of MMP-9 and MMP-2 after lung irradiation are involved in the inflammatory response associated with radiation-induced lung injury, and maybe further in radiation-induced lung fibrosis.

  11. Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression.

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    Hussein Atta

    Full Text Available Hepatocyte growth factor (HGF gene transfer inhibits liver fibrosis by regulating aberrant cellular functions, while mutant matrix metalloproteinase-9 (mMMP-9 enhances matrix degradation by neutralizing the elevated tissue inhibitor of metalloproteinase-1 (TIMP-1. It was shown that ASH1 and EZH2 methyltransferases are involved in development of liver fibrosis; however, their role in the resolution phase of liver fibrosis has not been investigated. This study evaluated the role of ASH1 and EZH2 in two mechanistically different therapeutic modalities, HGF and mMMP-9 gene transfer in CCl4 induced rat liver fibrosis. Liver fibrosis was induced in rats with twice a week intraperitoneal injection of CCl4 for 8 weeks. Adenovirus vectors encoding mMMP-9 or HGF genes were injected through tail vein at weeks six and seven and were sacrificed one week after the second injection. A healthy animal group was likewise injected with saline to serve as a negative control. Rats treated with mMMP-9 showed significantly lower fibrosis score, less Sirius red stained collagen area, reduced hydroxyproline and ALT concentration, decreased transforming growth factor beta 1 (TGF-β1 mRNA and lower labeling indices of α smooth muscle actin (α-SMA and proliferating cell nuclear antigen (PCNA stained cells compared with HGF- or saline-treated rats. Furthermore, TIMP-1 protein expression in mMMP-9 group was markedly reduced compared with all fibrotic groups. ASH1 and EZH2 protein expression was significantly elevated in fibrotic liver and significantly decreased in mMMP-9- and HGF-treated compared to saline-treated fibrotic livers with further reduction in the mMMP-9 group.Gene transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2 methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which underlines the central role of these enzymes during fibrogenesis. Future studies should evaluate the role of selective pharmacologic inhibitors

  12. HPA与MMP-9在肾癌中的表达及其与肿瘤微血管密度关系的研究%The expressions of HPA and MMP-9 in renal cell carcinoma and their relationship with the density of tumor angiogenesis

    Institute of Scientific and Technical Information of China (English)

    杨传楹; 刘久华; 梁宇

    2011-01-01

    Objective To determine the expressions and significance of heparanase (HPA) and matrix metalloproteinase -9 (MMP-9) in rcnal cell carcinoma. Methods The expressions of HPA, MMP-9 and CD34 in 40 cases of renal cell carcinoma and 10 normal kidney tissues were detected with immunohistochemistry-SP. Results The expressions of HPA, MMP-9 and CD34 were higher in renal cell carcinoma than in the normal kidney tissues. The expressions of HPA and MMP-9 were positively correlated ( r=0.352, P<0.05) in renal cell carcinoma. The expressions of HPA and MMP-9 in cases with and without lymph node metastasis were significantly different (P <0. 05). HPA and MMP-9 were differently expressed in well-differentiated cancer, moderately differentiated carcinoma and poorly differentiated carcinoma ( P < 0. 05). The expression of HPA and MMP-9 in renal cell carcinoma had no relation with the patients' age, gender (P > 0. 05).Conclusions The expressions of HPA and MMP-9 are closcly related with the genesis, dcvelopment, biological behavior and prognosis of renal cell carcinoma, the detection of which can serve as important markers for the early diagnosis and prognosis of renal cell carcinoma.%目的 检测乙酰肝素酶(HPA)与基质金属蛋白酶-9(MMP-9)在肾癌组织中的表达,探讨它们在肾癌发生发展中的临床意义.方法 采用免疫组化SP法检测40例肾癌、10例正常肾组织中HPA与MMP-9及CD34的表达,并记数CD34标记的肿瘤微血管密度(MVD)的表达情况.结果 肾癌组织中HPA与MMP-9及CD34的表达高于正常肾组织,HPA与MMP-9两者在肾癌中表达水平成正相关(r=0.352,P<0.05),其中淋巴结转移组HPA与MMP-9的表达与淋巴结未转移组间差异有统计学意义(P <0.05).HPA与MMP-9的表达在高分化癌、中分化癌和低分化癌中的差别有统计学意义(P<0.05).HPA与MMP-9在肾癌细胞中的表达与患者年龄、性别无关(P>0.05).结论 HPA与MMP-9的表达与肾癌的发生、发展、

  13. Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma

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    Francesca S. M. Tang

    2015-01-01

    Full Text Available Background. Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood and suboptimal (ASubopt asthma symptom control. Methods. Peripheral blood neutrophils from AGood (ACQ 0.75, n=7, and healthy controls (HC (n=9 were stimulated with bacterial (LPS (1 μg/mL, fMLF (100 nM, and viral (imiquimod (3 μg/mL, R848 (1.5 μg/mL, and poly I:C (10 μg/mL surrogates or live rhinovirus (RV 16 (MOI1. Cell-free supernatant was collected after 1 h for neutrophil elastase (NE and matrix metalloproteinase- (MMP- 9 measurements or after 24 h for CXCL8 release. Results. Constitutive NE was enhanced in AGood neutrophils compared to HC. fMLF stimulated neutrophils from ASubopt but not AGood produced 50% of HC levels. fMLF induced MMP-9 was impaired in ASubopt and AGood compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1 and FEV1/FVC. ASubopt and AGood responded similarly to other stimuli. Conclusions. Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.

  14. 结直肠癌患者血清中CEA、MMP-2和MMP-9表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    何秀丽

    2010-01-01

    目的:检测结直肠癌患者和血清中CEA、MMP-2和MMP-9的表达水平,探讨其临床意义.方法:收集300例经术后病理确诊为结直肠腺癌的患者作为观察组,100例健康成人血清作为正常对照组,应用酶联免疫吸附实验检测血清中CEA、MMP-2和MMP-9的含量.结果:观察组血清中CEA、MMP-2和MMP-9表达量显著高于对照组,血清中CEA、MMP-2和MMP-9的表达量与分化程度及Dukes分期密切相关.结论:结直肠癌患者血清中CEA、MMP-2和MMP-9高表达,三者在结直肠癌发生发展中起重要作用;早期联合检测血清中CEA、MMP-2和MMP-9的表达可能对判断预后及指导治疗有一定价值.

  15. MMP-9 and MMP-2 Contribute to Neuronal Cell Death in iPSC Models of Frontotemporal Dementia with MAPT Mutations

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    Md Helal U. Biswas

    2016-09-01

    Full Text Available How mutations in the microtubule-associated protein tau (MAPT gene cause frontotemporal dementia (FTD remains poorly understood. We generated and characterized multiple induced pluripotent stem cell (iPSC lines from patients with MAPT IVS10+16 and tau-A152T mutations and a control subject. In cortical neurons differentiated from these and other published iPSC lines, we found that MAPT mutations do not affect neuronal differentiation but increase the 4R/3R tau ratio. Patient neurons had significantly higher levels of MMP-9 and MMP-2 and were more sensitive to stress-induced cell death. Inhibitors of MMP-9/MMP-2 protected patient neurons from stress-induced cell death and recombinant MMP-9/MMP-2 were sufficient to decrease neuronal survival. In tau-A152T neurons, inhibition of the ERK pathway decreased MMP-9 expression. Moreover, ectopic expression of 4R but not 3R tau-A152T in HEK293 cells increased MMP-9 expression and ERK phosphorylation. These findings provide insights into the molecular pathogenesis of FTD and suggest a potential therapeutic target for FTD with MAPT mutations.

  16. Melatonin inhibits MMP-9 transactivation and renal cell carcinoma metastasis by suppressing Akt-MAPKs pathway and NF-κB DNA-binding activity.

    Science.gov (United States)

    Lin, Yung-Wei; Lee, Liang-Ming; Lee, Wei-Jiunn; Chu, Chih-Ying; Tan, Peng; Yang, Yi-Chieh; Chen, Wei-Yu; Yang, Shun-Fa; Hsiao, Michael; Chien, Ming-Hsien

    2016-04-01

    Renal cell carcinoma (RCC) is the most lethal of all urological malignancies because of its potent metastasis potential. Melatonin exerts multiple tumor-suppressing activities through antiproliferative, proapoptotic, and anti-angiogenic actions and has been tested in clinical trials. However, the antimetastastic effect of melatonin and its underlying mechanism in RCC are unclear. In this study, we demonstrated that melatonin at the pharmacologic concentration (0.5-2 mm) considerably reduced the migration and invasion of RCC cells (Caki-1 and Achn). Furthermore, we found that melatonin suppressed metastasis of Caki-1 cells in spontaneous and experimental metastasis animal models. Mechanistic investigations revealed that melatonin transcriptionally inhibited MMP-9 by reducing p65- and p52-DNA-binding activities. Moreover, the Akt-mediated JNK1/2 and ERK1/2 signaling pathways were involved in melatonin-regulated MMP-9 transactivation and cell motility. Clinical samples revealed an inverse correlation between melatonin receptor 1A (MTNR1A) and MMP-9 expression in normal kidney and RCC tissues. In addition, a higher survival rate was found in MTNR1A(high) /MMP-9(low) patients than in MTNR1A(low) /MMP-9(high) patients. Overall, our results provide new insights into the role of melatonin-induced molecular regulation in suppressing RCC metastasis and suggest that melatonin has potential therapeutic applications for metastastic RCC.

  17. Collagen XVI induces expression of MMP9 via modulation of AP-1 transcription factors and facilitates invasion of oral squamous cell carcinoma.

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    Konstanze B Bedal

    Full Text Available Collagen XVI belongs to the family of fibril-associated collagens with interrupted triple helices (FACIT. It is overexpressed during the progression of oral squamous cell carcinoma (OSCC. The present data show a strong collagen XVI-dependent induction of MMP9 and an increase in OSCC cell invasion. We found activated integrin-linked kinase (ILK in a complex with kindlin-1 and activation of protein kinase B (PKB/Akt to be responsible for MMP9 induction. Inhibition of the formation of focal adhesions reduced MMP9 expression. Moreover, collagen XVI overexpressing OSCC cell clones (COLXVI cell clones transfected with vectors containing different MMP9 promoter fragments adjacent to a luciferase reporter revealed an increase in luciferase signal dependent on AP-1 binding sites. Deletion of the AP-1 binding site 98 bp upstream of the reported transcription start site and inhibition of AP-1 with Tanshinone IIA resulted in decreased MMP9 expression. The AP-1 subunit JunB showed differential expression between COLXVI cell clones and mock control cells. Additionally, mass spectrometric analysis of immunoprecipitates revealed that c-Fos interacted strongly with dyskerin in COLXVI cell clones compared to mock controls.

  18. Collagen XVI induces expression of MMP9 via modulation of AP-1 transcription factors and facilitates invasion of oral squamous cell carcinoma.

    Science.gov (United States)

    Bedal, Konstanze B; Grässel, Susanne; Oefner, Peter J; Reinders, Joerg; Reichert, Torsten E; Bauer, Richard

    2014-01-01

    Collagen XVI belongs to the family of fibril-associated collagens with interrupted triple helices (FACIT). It is overexpressed during the progression of oral squamous cell carcinoma (OSCC). The present data show a strong collagen XVI-dependent induction of MMP9 and an increase in OSCC cell invasion. We found activated integrin-linked kinase (ILK) in a complex with kindlin-1 and activation of protein kinase B (PKB/Akt) to be responsible for MMP9 induction. Inhibition of the formation of focal adhesions reduced MMP9 expression. Moreover, collagen XVI overexpressing OSCC cell clones (COLXVI cell clones) transfected with vectors containing different MMP9 promoter fragments adjacent to a luciferase reporter revealed an increase in luciferase signal dependent on AP-1 binding sites. Deletion of the AP-1 binding site 98 bp upstream of the reported transcription start site and inhibition of AP-1 with Tanshinone IIA resulted in decreased MMP9 expression. The AP-1 subunit JunB showed differential expression between COLXVI cell clones and mock control cells. Additionally, mass spectrometric analysis of immunoprecipitates revealed that c-Fos interacted strongly with dyskerin in COLXVI cell clones compared to mock controls.

  19. Expression of gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors.

    Science.gov (United States)

    Lipari, L; Mauro, A; Gallina, S; Tortorici, S; Buscemi, M; Tete, S; Gerbino, A

    2012-01-01

    Salivary gland tumors, most of which are rare benign tumors, represent a histologically heterogenous group with the greatest diversity of morphological and cellular features. The aim of this study is to analyse the expression and possible interactions between gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors. We investigated the expression of gelatinases and cyclooxigenases in control salivary gland, Pleomorphic adenoma and Warthin's tumor through immunohistochemistry and Reverse Transcription - Polymerase Chain Reaction (PCR). We identified the expression of both classes of enzyme in normal samples and in the two types of pathological samples without any quantitative differences. From the present data no significant differences emerge in the expression of these enzymes among the different pathologies examined. Nevertheless, due to the small number of samples included in this study, general statements regarding correlation between the degree of severity of the tumoral pathology and the quantitative expression of these potential tumoral markers can not be made.

  20. Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3'-diindolylmethane in thyroid cancer.

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    Shilpi Rajoria

    Full Text Available BACKGROUND: Thyroid cancer is the most common endocrine related cancer with increasing incidences during the past five years. Current treatments for thyroid cancer, such as surgery or radioactive iodine therapy, often require patients to be on lifelong thyroid hormone replacement therapy and given the significant recurrence rates of thyroid cancer, new preventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,3'-diindolylmethane (DIM, to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor. METHODOLOGY/PRINCIPAL FINDINGS: Thyroid cancer cell lines were treated with estrogen and/or DIM and subjected to in vitro adhesion, migration and invasion assays to investigate the anti-metastatic and anti-estrogenic effects of DIM. We observed that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E(2 enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9. CONCLUSION/SIGNIFICANCE: Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiol enhanced thyroid cancer cell proliferation and in vitro metastasis associated events, namely adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determined to be targets of DIM. This anti-estrogen like property of DIM may lead to the development of a novel preventive and/or therapeutic dietary supplement for thyroid cancer patients by targeting progression of the disease.

  1. Effect of hyperbaric oxygen on MMP9/2 expression and motor function in rats with spinal cord injury.

    Science.gov (United States)

    Hou, Ying-Nuo; Ding, Wen-Yuan; Shen, Yong; Yang, Da-Long; Wang, Lin-Feng; Zhang, Peng

    2015-01-01

    To study the effect of hyperbaric oxygen intervention on the microenvironment of nerve regeneration after spinal cord injury modeling and to explore the possible mechanism of nerve regeneration and functional recovery in rats with spinal cord injury. In 98 adult female SD rats, 90 successful models were obtained, which were divided into sham group, spinal cord injury group and hyperbaric oxygen group using randomized block method, 30/group. Spinal cord injury rat model was established in accordance with the modified Allen method. Motor function was assessed at the time points of before modeling, one day, three days, one week, two weeks, three weeks and four weeks after modeling respectively by BBB rating, inclined plane test and improved Tarlov score. At 3 days after modeling, apoptosis of neuronal cells in spinal cord injury region in experimental group was detected by TUNEL method; gene and protein expression of MMP9/2 in spinal cord injury and surrounding tissues was detected by RT-PCR and Western blot assay. At 4 weeks after modeling, histopathological morphological changes in spinal cord injury were observed by HE staining; fluorogold retrograde tracing was used to observe the regeneration and distribution of spinal cord nerve fibers and axon regeneration was observed by TEM. The three motor function scores in hyperbaric oxygen group at each time point after two weeks of treatment were significantly increased compared with spinal cord injury group (P hyperbaric oxygen group were significantly lower than those in spinal cord injury group (P hyperbaric oxygen group was significantly lower (P hyperbaric oxygen group and spinal cord injury group in order; the differences among the groups were statistically significant (P hyperbaric oxygen group; unmyelinated and myelinated nerve fibers in hyperbaric oxygen group were more than those in spinal cord injury group. Hyperbaric oxygen therapy played a protective effect on spinal cord injury through reducing apoptosis of

  2. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    Science.gov (United States)

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.

  3. Cationic star-shaped polymer as an siRNA carrier for reducing MMP-9 expression in skin fibroblast cells and promoting wound healing in diabetic rats

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    Li N

    2014-07-01

    Full Text Available Na Li,1,* Heng-Cong Luo,1,* Chuan Yang,1 Jun-Jie Deng,2 Meng Ren,1 Xiao-Ying Xie,1 Diao-Zhu Lin,1 Li Yan,1 Li-Ming Zhang2 1Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2DSAPM Lab and PCFM Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Excessive expression of matrix metalloproteinase-9 (MMP-9 is deleterious to the cutaneous wound-healing process in the context of diabetes. The aim of the present study was to explore whether a cationic star-shaped polymer consisting of ß-cyclodextrin (ß-CD core and poly(amidoamine dendron arms (ß-CD-[D3]7 could be used as the gene carrier of small interfering RNA (siRNA to reduce MMP-9 expression for enhanced diabetic wound healing. Methods: The cytotoxicity of ß-CD-(D37 was investigated by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay (MMT method in the rat CRL1213 skin fibroblast cell line. The transfection efficiency of ß-CD-(D37/MMP-9-small interfering RNA (siRNA complexes was determined by confocal microscopy and flow cytometry. Quantitative real time (RT polymerase chain reaction was performed to measure the gene expression of MMP-9 after the transfection by ß-CD-(D37/MMP-9-siRNA complexes. The ß-CD-(D37/MMP-9-siRNA complexes were injected on the wounds of streptozocin-induced diabetic rats. Wound closure was measured on days 4 and 7 post-wounding. Results: ß-CD-(D37 exhibited low cytotoxicity in fibroblast cells, and easily formed the complexes with MMP-9-siRNA. The ß-CD-(D37/MMP-9-siRNA complexes were readily taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene expression (P<0.01. Animal experiments revealed that the treatment by ß-CD-(D37/MMP-9-siRNA complexes enhanced wound

  4. 类风湿关节炎和骨关节炎滑膜滑液中MMP-2和MMP-9的比较%Comparison of the MMP-2 and MMP-9 in the Knee Joint Synovial Fluid and Synovial Membrane in Patients with active Rheumatoid Arthritis and Osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    刘荣清; 林佳静; 孙伯坚; 李海波; 宋婷阁; 韩梅

    2013-01-01

    目的 检测基质金属蛋白酶-2(matrix metalloproteinases-2,MMP-2)和基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)在类风湿关节炎活动期(rheumatoid arthritis,RA)和骨关节炎(osteoarthritis,OA)活动期膝关节滑液及滑膜中的含量,并探讨两者在RA和OA病变中的作用.方法 收集宁夏医科大学总医院风湿免疫科和骨科确诊的14例RA活动期患者和24例OA活动期患者的膝关节滑液和滑膜组织,用酶联免疫吸附实验(ELISA)检测滑液中MMP-2和MMP-9的含量,用免疫组化法检测滑膜组织中MMP-9的相对表达量,组间比较采用秩和检验.结果 RA活动期患者膝关节滑液中的MMP-2和MMP-9浓度明显高于骨关节炎活动期患者(P<0.01);RA活动期患者膝关节滑膜中MMP-9的相对表达量明显高于OA活动期患者(P<0.01).结论 MMP-2和MMP-9在RA活动期患者滑液中高表达,MMP-9在RA活动期患者滑膜中高表达,可能参与RA发生发展过程中滑膜炎、骨质破坏.%Objective To compare matrix metalloproteinases - 2 ( MMP - 2) and matrix metalloproteinases - 9 ( MMP - 9) in knee joint synovial fluid and synovial membrane in patients with active rheumatoid arthritis ( RA) and active osteoarthritis ( OA) , and to explore the effects of MMP -2 and MMP -9 on lesion of RA and OA. Methods Knee joint synovial fluid and synovial membrane were collected from 14 and 24 patients with final diagnosis of RA and OA, and underwent surgery at the General Hospital of Ningxia Medical University. MMP - 2 and MMP - 9 in the synovial fluid were measured by enzyme linked immunosorbent assay (ELISA). The distributions of MMP - 9 in the synovial membrane were analyzed using immunohistochemistry. Student's t - test was used for intergroup comparison. Results The level of MMP - 2 and MMP - 9 in synovial fluid of active RA was significantly higher than that of active OA(P <0. 01) ; the relative expression of MMP -9 in synovial membrane was stronger in active RA

  5. The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake

    DEFF Research Database (Denmark)

    Hvidberg, Vibeke; Jacobsen, Christian; Strong, Roland K

    2005-01-01

    in delivering iron to cells during formation of the tubular epithelial cells of the primordial kidney. No cellular receptor for NGAL has been described. We show here that megalin, a member of the low-density lipoprotein receptor family expressed in polarized epithelia, binds NGAL with high affinity, as shown...

  6. Accuracy of Neutrophil Gelatinase-Associated Lipocalin in Detecting Acute Kidney Injury after Urogenital Robotic Assisted Laparoscopic Surgery under General Anesthesia

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    Orsolya MIHÁLY

    2012-06-01

    Full Text Available The aim of this study was to demonstrate the accuracy of NGAL in detecting acute kidney injury (AKI after urogenital robotic surgery in general anesthesia. Methods: A prospective longitudinal observational study, which included patients scheduled for elective robotic surgery under general anesthesia. The serum and urine NGAL at induction, 6 hours and 12 hours were determined. Serum creatinine was measured preoperatively and daily 4 days postoperatively. AKI was defined as the absolute growth of serum creatinine by 0.3 mg/dl over baseline within 48 hours postoperatively. Results: 24 patients were enrolled in the study. AKI occurred in 38% of patients. Serum NGAL increased significantly at 6 hours and 12h, compared to baseline, with a higher increase in the group of patents without AKI. There were no significant results for urine NGAL. A link was observed between the values of serum NGAL, with associated significance p<0.0001. The correlations between urine NGAL were not significant. The predictive value of NGAL, analyzed by cross-tabulation, OR was 3 for baseline value and 5.33 for the values measured at 6 hours and 12 hours, but with no statistical significance. Conclusions: The modifications of the NGAL levels, measured at 6 hours and 12 hours from the induction of anesthesia, were significant with more importance at 6 hours and in patients without AKI. Serum NGAL had no predictive value for AKI, but the risk to develop AKI was 3 times higher for baseline determination and 5 times at 6 and 12 hours.

  7. Serum and urinary neutrophil gelatinase-associated lipocalin as a predictor of rat kidney histopathology in an early ischemia-reperfusion model

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    Sahala Panggabean

    2012-11-01

    Full Text Available Background: The severity of ischemia-reperfusion (I/R kidney injury is highly correlated with mortality and morbidity rate. Research on human and animal prove that NGAL predicts kidney injury at early phase. The objective of this study is to prove that the increase in serum and urinary NGAL are correlated with kidney tubular epithelial damage, and this increase has occurred in initiation phase, indicated by rat kidney histopathology in an early I/R model.Methods: Twenty eight male Sprague-Dawley rats were divided into 4 groups: 4 hour sham (Sham 4, 8 hour sham (Sham 8, 10 minute ischemia 4 hour reperfusion (I/R 4 and 10 minute ischemia 8 hour reperfusion (I/R 8. Blood, urine and kidney samples were collected. Serum creatinine level was analyzed with Jaffe method, while serum and urinary NGAL level were analyzed with direct sandwich ELISA method. Evaluation of kidney damage were measured semi quantitatively in tissue stained with HE. Further evaluation to confirm cellular changes on kidney was performed by electron microscope and immunohistochemistry.Results: Serum NGAL was found significantly correlated with degree of kidney tissue damage (ρSpearman NGAL serum = 0.701, p < 0.001, also urinary NGAL (ρSpearman = 0.689, p < 0.001. NGAL expression differs significantly between I/R group and sham (t-test, t = -26635.056, p < 0.001, also kidney damage (t-test, t = -5.028, p < 0.001, and serum and urinary NGAL levels (Mann-Whitney, U = 0, p < 0.001. With cutoff points of 136.95 ng/mL and 58.69 ng/mL subsequently for serum and urinary NGAL , it is found that sensitivity = 1, specificity = 1.Conclusion: Elevation of serum and urinary NGAL are significantly correlated with epithelial tubular kidney damage on rat undergoing early ischaemia reperfusion. (Med J Indones. 2012;21:208-13Keywords: Early I/R kidney injury, kidney histopathology, NGAL

  8. Expression of NRL/NGAL (neu-related lipocalin/neutrophil gelatinase-associated lipocalin) during mammalian embryonic development and in inflammation.

    Science.gov (United States)

    Zerega, B; Cermelli, S; Michelis, B; Cancedda, R; Cancedda, F D

    2000-03-01

    The neu-related lipocalin (NRL) is a protein overexpressed in rat mammary cancer induced by activated neu (HER-2/c-erbB2). This protein belongs to the family of the lipocalins or low molecular weight proteins able to bind and transport small hydrophobic molecules. The NRL homologue in mouse is SIP24, an acute phase protein induced in the animal by turpentine injection; the human homologous protein is NGAL expressed in granulocytes and epithelial cells in pathological conditions, such as inflammation and malignancy. We have investigated NRL expression in developing rat embryos. By immunolocalization we have shown localization of the protein in the hypertrophic region of growth plate cartilage. NRL was particularly enriched in prehypertrophic chondrocytes. In addition, we observed localization of the protein in forming skeletal muscle fibres and in the myocardium of developing heart. In agreement with the immunolocalization data, by in situ hybridization we have demonstrated the presence of the specific mRNA in the same tissues. At an early stage of differentiation, cultured rat embryo-derived chondrocytes did not express NRL; nevertheless expression of the protein was induced in these cells by treatment with an inflammatory agent, such as LPS. By Western blot analysis with specific antibodies we showed protein synthesis by cultured myoblasts also in the absence of LPS treatment, but only when forming myotubes were observed in culture. Stimulation of myoblast cultures with LPS resulted in an enhancement of the NRL expression in well formed myotubes. Our data suggest a role of NRL in cartilage and muscle differentiation. NRL expression was induced by inflammatory agents. We wish to propose that the expression of NRL in hypertrophic chondrocytes and forming myotubes is part of a "physiological" acute phase response occurring during cartilage and muscle development. In this manuscript we also report that NRL is not detectable by immunolocalization in adult cartilage (both articular and tracheal) from normal subjects. On the contrary articular cartilage from osteoarthritic patients was highly positive for the presence of NRL/NGAL. Interestingly the expression of this protein is also activated during neoplastic transformation of chondrogenic lineage cells.

  9. Urine/Plasma Neutrophil Gelatinase Associated Lipocalin Ratio Is a Sensitive and Specific Marker of Subclinical Acute Kidney Injury in Mice.

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    Tamás Kaucsár

    Full Text Available Detection of acute kidney injury (AKI is still a challenge if conventional markers of kidney function are within reference range. We studied the sensitivity and specificity of NGAL as an AKI marker at different degrees of renal ischemia.Male C57BL/6J mice were subjected to 10-, 20- or 30-min unilateral renal ischemia, to control operation or no operation, and AKI was evaluated 1 day later by histology, immunohistochemistry, BUN, creatinine, NGAL (plasma and urine and renal NGAL mRNA expression.A short (10-min ischemia did not alter BUN or kidney histology, but elevated plasma and urinary NGAL level and renal NGAL mRNA expression although to a much smaller extent than longer ischemia. Surprisingly, control operation elevated plasma NGAL and renal NGAL mRNA expression to a similar extent as 10-min ischemia. Further, the ratio of urine to plasma NGAL was the best parameter to differentiate a 10-min ischemic injury from control operation, while it was similar in the non and control-operated groups.These results suggest that urinary NGAL excretion and especially ratio of urine to plasma NGAL are sensitive and specific markers of subclinical acute kidney injury in mice.

  10. The Usefulness of Determining Neutrophil Gelatinase-Associated Lipocalin Concentration Excreted in the Urine in the Evaluation of Cyclosporine A Nephrotoxicity in Children with Nephrotic Syndrome

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    Ewa Gacka

    2016-01-01

    Full Text Available Introduction. The use of cyclosporine (CsA in the treatment of nephrotic syndrome (NS contributed to a significant reduction in the amount of corticosteroids used in therapy and its cumulative side effects. One of the major drawbacks of CsA therapy is its nephrotoxicity. Prolonged CsA treatment protocols require sensitive, easily available, and simple to measure biomarkers of nephrotoxicity. NGAL is an antibacterial peptide, excreted by cells of renal tubules in response to their toxic or inflammatory damage. Aim of the Study. The aim of this study was to assess the suitability of the NGAL concentration in the urine as a potential biomarker of the CsA nephrotoxicity. Material and Methods. The study was performed on a group of 31 children with NS treated with CsA. The control group consisted of 23 children diagnosed with monosyptomatic enuresis. The relationship between NGAL excreted in urine and the time of CsA treatment, concentration of CsA in blood serum, and other biochemical parameters was assessed. Results. The study showed a statistically significant positive correlation between urine NGAL concentration and serum triglycerides concentration and no correlation between C0 CsA concentration and other observed parameters of NS. The duration of treatment had a statistically significant influence on the NGAL to creatinine ratio. Conclusions. NGAL cannot be used alone as a simple CsA nephrotoxicity marker during NS therapy. Statistically significant correlation between NGAL urine concentration and the time of CsA therapy indicates potential benefits of using this biomarker in the monitoring of nephrotoxicity in case of prolonged CsA therapy.

  11. The role of neutrophil gelatinase-associated lipocalin in predicting acute kidney injury in patients undergoing off-pump coronary artery bypass graft: A pilot study

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    Vishal Jain

    2016-01-01

    Full Text Available Objective: Acute kidney injury (AKI is a commonly encountered postoperative complication after cardiac surgery especially in high risk patients. AKI though seen more commonly after conventional on pump coronary artery bypass surgery (CCABG, is not uncommon after off pump coronary bypass surgery (OPCAB. Various biomarkers have shown promise over last one decade as an early marker for predicting AKI postoperatively. NGAL is one such biomarker whose concentration is increased in urine after any nephrotoxic and ischemic insult. The objective of this study was to assess the role of urine NGAL in predicting AKI after OPCAB in patients with increased risk of developing AKI. Design: A prospective cohort study. Setting: A clinical study in a multi specialty hospital. Participants: Eighty patients. Materials and Methods: study was approved by the hospital research ethics committee. 80 patients posted for OPCAB with an increased risk of developing AKI defined as having a Cleveland Clinic Foundation Acute renal failure scoring System score of ≥6 were included in the study. Patients with coronary angiography (CAG within 48 hrs prior to surgery, pre-existing AKI, preoperative renal replacement therapy (RRT and CKD stage 5 were excluded. Urine NGAL level before the start of surgery baseline and at 4 hrs post surgery were done. Renal function tests were assessed on the day of surgery (4 hrs post surgery and on the next three days. Result: Seven patients developed AKI as defined by acute kidney infection network (AKIN and risk injury failure loss end stage (RIFLE criteria for AKI. NGAL value at 4 hrs in patients who developed AKI was significantly higher than in those patients who did not develop AKI (P < 0.05. Conclusion: urine NGAL is an early biomarker of acute kidney injury in patients undergoing OPCAB surgeries. However, large multicentre studies may be needed to confirm it.

  12. Mangiferin regulates proliferation and apoptosis in glioma cells by induction of microRNA-15b and inhibition of MMP-9 expression.

    Science.gov (United States)

    Xiao, Jinsong; Liu, Li; Zhong, Zian; Xiao, Cheng; Zhang, Junjian

    2015-06-01

    Mangiferin, a flavonoid extracted from the leaves of the Anacardiaceae plant, the mango tree, has physiological activity and pharmacological effects in many aspects. The present study aimed to clarify the effect of mangiferin on proliferation and apoptosis of glioma cells and the mechanism of these curative effects of mangiferin. In this experiment, we detected the proliferation using 3-(4,5-dimethylthylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Then, cell apoptosis of U87 glioma cells was measured with the Annexin V-FITC/propidium iodide (PI) apoptosis detection kit, DAPI staining assay and the caspase-3 and caspase-9 activity assay kit. Next, quantitative real-time PCR and gelatin zymography were used to analyze the expression of microRNA-15b (miR-15b) and matrix metalloproteinase-9 (MMP-9), respectively. MMP-9 agonist, miR-15b mimics and anti-miR-15b mimics were added to the U87 glioma cells for elucidating the mechanisms involved in the curative effects of mangiferin. In the present study, mangiferin notably restrained the proliferation and increased the apoptosis of the U87 glioma cells. Meanwhile, mangiferin specifically promoted the expression of miR-15b and suppressed the level of MMP-9 in the U87 glioma cells. miR-15b regulated the expression of MMP-9 in the U87 glioma cells. MMP-9 agonist and anti-miR‑15b reduced the curative effects of mangiferin in the U87 glioma cells. In summary, mangiferin regulates proliferation and apoptosis in glioma cells by induction of miR-15b and inhibition of MMP-9 expression.

  13. 缺氧对Tca83细胞中HIF-1α与MMP-9表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘长富; 王稚英; 于涛

    2013-01-01

    目的 探讨缺氧对体外培养的人舌癌Tca83细胞中缺氧诱导因子(hypoxia inducible factor,HIF)1 α及基质金属蛋白酶(matrix metaloproteinases)-9表达的影响.方法 以CoCl2浓度为150 mmol/L的DMEM培养基体外培养Tca83细胞,分别为4、8、12、24h,以未含CoC12的培养基作空白对照组,采用免疫荧光染色检测Tca83细胞中HIF-1α及MMP-9的表达,分析缺氧时间不同对两种蛋白表达的影响.结果 常氧条件下,HIF-1α与MMP-9的表达较弱.而缺氧条件下,HIF-1 α与MMP-9表达明显增强,且随缺氧时间的延长,HIF-1 α与MMP-9表达逐渐增强.结论 应用浓度为150 mmol/L的CoCl2可以诱导Tca83细胞发生缺氧,缺氧可诱导Tca83细胞中HIF-1 α与MMP-9表达增强,且HIF-1 α与MMP-9表达水平随缺氧时间的延长而增强.

  14. MT1-MMP expression level status dictates the in vitro action of lupeol on inflammatory biomarkers MMP-9 and COX-2 in medulloblastoma cells.

    Science.gov (United States)

    Annabi, Borhane; Vaillancourt-Jean, Eric; Béliveau, Richard

    2013-02-01

    Local inflammation-induced extracellular matrix structural changes are a prerequisite to neoplastic invasion by pediatric intracranial tumors. Accordingly, increased expression of matrix metalloproteinases MMP-2 and MMP-9, two inflammation-induced matrix metalloproteinases (MMPs), may further aid the transformed cells either to infiltrate adjacent tissues or to enter the peripheral circulation. In the context of neuroinflammation, MMP-9 has been linked to processes such as blood-brain barrier opening and invasion of neural tissue by blood-derived immune cells. Given its reported anti-inflammatory and anticancer properties, we investigated the in vitro pharmacological effects of lupeol, a diet-derived triterpenoid, on MMP-9 and cyclooxygenase (COX)-2 expressions in a pediatric medulloblastoma DAOY cell line model. Lupeol was unable to inhibit the increased MMP-9 and COX-2 expression in phorbol 12-myristate 13-acetate (PMA)-treated cells, but was rather found to synergize with PMA to induce both biomarkers' expression. A contribution of the membrane type-1 (MT1)-MMP was also revealed, since lupeol/PMA treatments triggered proMMP-2 activation, and that MT1-MMP gene silencing reversed the combined effects of lupeol/PMA on both MMP-9 and COX-2. The mRNA stabilizing factor HuR was also found increased in the combined lupeol/PMA treatment, suggesting stabilization processes of the MMP-9 and COX-2 transcripts. We postulate that lupeol's anti-inflammatory properties may exert better pharmacological action within low MT1-MMP expressing tumors. Furthermore, these evidences add up to the new pleiotropic molecular mechanisms of action of MT1-MMP, and prompt for evaluating the future in vitro pharmacological properties of lupeol under pro-inflammatory experimental set-up.

  15. Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway.

    Science.gov (United States)

    Fan, Zhigang; Duan, Xiaoyi; Cai, Hui; Wang, Li; Li, Min; Qu, Jingkun; Li, Wanjun; Wang, Yongheng; Wang, Jiansheng

    2015-08-01

    Invasion and metastasis are the major causes of tumor-related mortality in lung cancer. It is believed that curcumin is an effective drug possessing anti-invasive and anti-metastatic activities in the treatment of cancer. However, the specific mechanisms remain unclear. In the present study, we investigated whether the PKCα/Nox-2/ATF-2/MMP-9 signaling pathway is involved in the invasive behavior of lung cancer and whether curcumin could inhibit invasion by modulating this pathway. The cytotoxic effect of curcumin was evaluated by MTT assay and the capacity of invasion was assessed by Transwell assay. siRNA and plasmid transfection techniques were used to study the function of targeted genes. Real-time PCR and western blot analysis were used to evaluate the expression levels of PKCα, Nox-2, MMP-9 and the phosphorylation of ATF-2. The results showed that curcumin inhibited the proliferation and invasion of A549 cells in a dose-dependent manner. Overexpression of MMP-9 enhanced the invasion of A549 cells. However, inhibition of MMP-9 by siRNA or curcumin suppressed cell invasion. Moreover, we also demonstrated the catalytic role of PKCα in expression of MMP-9 and cellular invasion in A549 cells, which was dependent on the expression of Nox-2 and phosphorylation of ATF-2. Finally, we also showed that curcumin dose-dependently reduced the expression of PKCα, P47phox, Nox-2 and phosphorylated ATF-2, as well as intracellular ROS generation, suggesting the inhibitory effect of curcumin on the activation of the PKCα/Nox-2/ROS/ATF-2 pathway. In conclusion, the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway is activated in lung cancer A549 cells, which could be modulated by curcumin to inhibit cell invasiveness.

  16. Functional Promoter Polymorphisms of MMP-2 C-735T and MMP-9 C-1562T and Their Synergism with MMP-7 A-181G in Multiple Sclerosis.

    Science.gov (United States)

    Rahimi, Zohreh; Abdan, Zahra; Rahimi, Ziba; Razazian, Nazanin; Shiri, Hadis; Vaisi-Raygani, Asad; Shakiba, Ebrahim; Vessal, Mahmood; Moradi, Mohammad-Taher

    2016-08-01

    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Matrix metalloproteinases (MMPs) play an important role in breakdown of blood-brain barrier, transmigration, and invasion of immune cells and formation of MS lesions. The aim of present study was to investigate the influence of MMP-2 C-735T and MMP-9 C-1562T variants and their synergism with MMP-7 A-181G on susceptibility to MS. In a case-control study 125 MS patients and 235 healthy individuals from Western Iran were investigated. The various genotypes of MMP-2, MMP-9, and MMP-7 were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In females the presence of MMP-2 C allele was associated with an increased risk of MS (OR = 1.69, p = 0.041). No significant difference was detected between the frequency of MMP-9 T allele in MS patients (8.2%) and controls (12.8%, p = 0.068). The concomitant presence of both MMP-2 C and MMP-7 G alleles was associated with 1.82-fold increased risk of MS (p = 0.002). Also, a synergism was detected between MMP-9 C and MMP-7 G alleles that elevated the risk of MS by 1.5-times (p = 0.035). The presence of haplotype MMP-9 T, MMP-7 G, and MMP-2 C (TGC) compared to haplotype CAG increased the risk of MS by 3.13-fold (p = 0.16). The present study suggests that gene-gene interactions and variants of more genes instead of single gene might play a role in susceptibility to MS. We indicated that synergism between variants of MMP-2, MMP-7, and MMP-9 genes might increase the risk of MS.

  17. MTA-1和 MMP-9在人宫颈癌组织中的表达与淋巴结转移的关系

    Institute of Scientific and Technical Information of China (English)

    李艳玲

    2016-01-01

    目的::讨转移相关因子-1(MTA-1)和基质金属蛋白酶-9(MMP-9)在人宫颈癌组织中的表达情况,及其与发生淋巴结转移的关系。方法:收集53例人宫颈癌组织设为观察组和40例人正常宫颈组织设为对照组。采用免疫组织化学法检测两组人宫颈组织中MTA-1和MMP-9的表达,并分析与淋巴结转移的关系。结果:观察组人宫颈癌组织中MTA-1和MMP-9的阳性率均显著高于对照组(P<0.05);MTA-1与MMP-9在人宫颈癌组织中的表达呈正相关(r=0.749,P<0.01);MTA-1和MMP-9均与人宫颈癌淋巴结转移呈正相关(P<0.05)。结论:MTA-1和MMP-9在人宫颈癌组织中异常高表达,这可能与人宫颈癌发生淋巴转移有关。

  18. Local Inflammation Alters MMP-2 and MMP-9 Gelatinase Expression Associated with the Severity of Nifedipine-Induced Gingival Overgrowth: a Rat Model Study.

    Science.gov (United States)

    Li, Wu-Li; Wu, Cheng-Hai; Yang, Jun; Tang, Min; Chen, Long-Jie; Zhao, Shou-Liang

    2015-08-01

    Nifedipine-induced gingival overgrowth (NIGO) is characterized by cell proliferation and extracellular matrix (ECM) component accumulation in gingival connective tissues, with varying degrees of inflammation and fibrosis. Impaired collagen and ECM homeostasis may be among the underlying molecular mechanisms that lead to the fibrotic changes that occur in drug-induced gingival overgrowth (DIGO). Because matrix metalloproteinases (MMPs) play vital roles in regulating collagen and ECM metabolism, many studies have been performed to reveal the relationship between MMPs and DIGO. It is thought that the gelatinases MMP-2 and MMP-9, both type IV collagenases, are involved in the development of tissue inflammation and organ fibrosis. However, the few studies regarding gelatinase expression in DIGO are controversial. Recent studies have demonstrated the inhibitory effect of cyclosporine A (CsA) on gelatinase expression and/or activity; however, similar changes have yet to be detected in Nif-treated gingival tissues. In this study, we verified that Nif treatment could lead to gingival overgrowth in rats and that gingival inflammation played a pro-proliferative role in NIGO development. Additionally, we examined the temporal expression of gelatinases on days 0, 7, 14, 21, 30, and 40 during NIGO development. The aim was to investigate whether MMP-2 and MMP-9 played significant roles in regulating NIGO development and progression. MMP-2 gene expression was not altered by Nif treatment alone but was significantly inhibited by Nif treatment for 30 days in the presence of local inflammation. However, no significant alterations in MMP-2 protein expression were detected in the Nif-treated gingival tissue, regardless of the presence or absence of local inflammation. Moreover, Nif treatment could lead to transient and significant increases in MMP-9 gene and protein expression levels in the presence of local inflammation. In particular, active MMP-9 expression increased significantly

  19. Use of matrix metalloproteinase-9 (MMP-9 and its tissue inhibitor (TIMP-1 in the pathomorphological diagnosis of carotid pathology: literature review and own observations

    Directory of Open Access Journals (Sweden)

    Yu. I. Kuzyk

    2016-01-01

    Full Text Available Matrix metalloproteinases (MMPs are the degradative enzymes of the extracellular matrix. Currently, the role of MMP-2 and MMP-9 in the progression of atherosclerosis (AS is proved. The question of possible involvement of MMP-9 into elastin degradation in fibromuscular dysplasia (FMD and pathological tortuosity (PT remains open and insufficiently explored. The aim of the study – analysis of the current literature on the role of degradative enzymes in the development of carotid pathology and study of the expression of type I, III, IV collagens, MMP-9 and TIPM-1 in the wall of the carotid arteries in FMD, PT and AS. Materials and methods included literature review and own research. Immunohistochemical study of type I, III and IV collagens, TIMP-1 and MMP-9 was carried out on surgical material of patients with main carotid diseases: three observations with AS, two – with FMD, two – with PT. The level of expression was assessed by semiquantitative method. Results. Own observations showed that in FMD types I and III collagen content in the media and in the adventitia remains unchanged. MMP-9 expression level reached the highest level of intensity in atherosclerotic plaques, particularly in macrophages, constituting the main part of the atheromatous mass. Moderate intensity of expression is noted in FMD and PT. In PT expression prevailed in the lower third of the media on the border with adventitia, including the adventitia, in FMD – mainly in the media. The level of TIMP-1 is weakly positive in PT and FMD, negative in AS. Conclusions. These results demonstrate the possibility of using MMP-9 and TIMP-1 as a morphological marker determining pathological processes in carotid pathology. Data of immunohistochemical study of type I, II, IV collagens indicate moderate expression of collagen type I in FMD and PT, severe expression of collagen III in FMD, moderate in PT. Type IV collagen is highly expressed in atherosclerotic plaques. For AS high

  20. IκB-α、MMP-9在食管癌中的表达及其生物学意义

    Institute of Scientific and Technical Information of China (English)

    刘亮; 王莉; 倪晓辰; 武中林; 王光大; 赵阳; 左静; 王静; 左连富

    2015-01-01

    目的检测核因子κB(NF-κB)的抑制蛋白α(inhibitor of NF-κBα,IκB-α)及基质金属蛋白酶9(matrix metalloprotein-9,MMP-9)在不同食管病变组织中的表达,探讨IκB-α、MMP-9与食管癌发生、发展及转移的关系。方法通过免疫组织化学检测食管鳞癌、食管不典型增生组织及食管正常黏膜组织中IκB-α、MMP-9蛋白的表达;分析食管鳞癌组织中IκB-α、MMP-9蛋白表达与不同临床病理特征的关系,并对食管鳞癌组织中IκB-α与MMP-9蛋白表达相关性进行分析。结果食管鳞癌组织中IκB-α蛋白的表达(80.0%)明显高于食管不典型增生组织(52.3%)及食管正常组织(8.3%),差异有统计学意义(P〈0.05),且与淋巴结转移及浸润深度有关。MMP-9蛋白在食管鳞癌组织中的表达(73.3%)明显高于食管不典型增生组织(71.4%)及食管正常组织(16.7%),差异有统计学意义(P〈0.05),且与细胞分化程度、淋巴结转移及浸润深度有关。食管癌组织中IκB-α与MMP-9蛋白表达差异无统计学意义(P〉0.05)。结论 IκB-α、MMP-9蛋白在食管癌组织中异常表达,参与了食管癌浸润、转移的发生。

  1. Paper de la gelatinassa B (MMP-9) en el desenvolupament d'edema en la fase aguda de l'hemorràgia intracerebral espontània

    OpenAIRE

    Abilleira i Castells, Sònia

    2002-01-01

    Descripció del recurs: 5 desembre 2002 Consultable des del TDX Títol obtingut de la portada digitalitzada Introducción: La gelatinasa B o MMP-9 es una metaloproteasa de matriz que ha sido relacionada con la disrupción de la barrera hematoencefálica en diversas enfermedades del SNC. Diversos trabajos han demostrado que el desarrollo de edema perihematoma (EPH) en la fase aguda de la hemorragia cerebral (HIC) se relaciona con el deterioro clínico de estos pacientes. El papel de MMP-9 e...

  2. 不同时期慢性阻塞性肺疾病患者与慢性阻塞性肺疾病合并肺间质纤维化患者血清MMP-9水平%THE LEVELS OF SERUM MMP-9 IN PATIENTS WITH DIFFERENT STAGES OF COPD AND COPD-PIF

    Institute of Scientific and Technical Information of China (English)

    支颜霄; 顾玉海

    2013-01-01

    目的 观察血清基质金属蛋白酶-9(MMP-9)与不同时期COPD和COPD合并肺间质纤维化的相关性.方法 选择COPD合并肺纤维化患者9例作为COPD-PIF组,COPD急性加重期患者20例作为AECOPD组,COPD缓解期患者31例作为COPD缓解组,健康体检人群26例作为对照组.抽取受试者清晨空腹静脉血,采用双抗体夹心ELISA法测定血清MMP-9水平.结果 COPD-PIF组患者血清MMP-9水平高于AECOPD组、COPD缓解组和对照组(P<0.05);AECOPD组患者血清MMP-9水平高于COPD缓解组和对照组(P <0.05);COPD缓解组患者血清MMP-9水平高于对照组(P<0.05).结论 血清MMP-9与肺间质纤维化的发生可能相关.

  3. 转化生长因子β调节培养的人角膜基质细胞MMP-2和MMP-9的分泌%TGF-β modulates secretion of MMP-2 and MMP-9 by cultured human corneal keratocytes

    Institute of Scientific and Technical Information of China (English)

    晏晓明; 王晓飞; 吴静安

    2000-01-01

    目的观察转化生长因子β(TGF-β)对培养的人角膜基质细胞分泌MMP-2和MMP-9的调节作用,探讨TGF-β治疗非感染性角膜溃疡的潜在可能性.方法采用酶谱法检测人角膜基质细胞MMP-2和MMP-9的分泌,并观察TGT-β对MMP-2和MMP-9分泌的调节作用.结果培养的人角膜基质细胞分泌MMP-2和MMP-9,TGF-β抑制MMP-9的活性,且随TGF-β质量浓度增加而增强,随TGF-β作用时间延长而增强;对MMP-2的活性,TGF-β有较弱的促进作用.结论TGF-β作为一种MMP-9的抑制剂,在促进非感染性角膜溃疡愈合方面很有潜力.

  4. Relation between expression of MMP-2 and MMP-9 and invasion,metastasis of epithelial carcinoma of ovary%MMP-2和MMP-9表达与卵巢上皮性癌侵袭转移的关系

    Institute of Scientific and Technical Information of China (English)

    王晓燕; 张艳开; 任国春

    2004-01-01

    目的研究基质金属蛋白酶(MMP-2和MMP-9)在卵巢上皮性癌组织中的表达,探讨MMP-2、MMP-9表达与肿瘤的侵袭转移及预后的关系.方法用免疫组化S-P法对47例卵巢上皮性癌组织中MMP-2和MMP-9的表达情况进行检测.结果 MMP-2和MMP-9的表达在卵巢上皮性癌各组织类型之间差异无显著性,但在临床分期、初发、复发及细胞分级之间差异有显著性.MMP-2和MMP-9的表达与生存时间呈负相关.结论 MMP-2、MMP-9与卵巢上皮性癌的侵袭转移及预后有关.

  5. Expression of MMP-2 and MMP-9 in vitrectomy specimens with proliferative diabetic retinopathy%增生性糖尿病视网膜病变玻璃体切除物中MMP-2和MMP-9的表达

    Institute of Scientific and Technical Information of China (English)

    赵宏; 张效房

    2007-01-01

    目的:检测增生性糖尿病视网膜病变(PDR)玻璃体切除物中基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的表达,探讨2者在PDR发生发展中的作用.方法:使用逆转录多聚酶链反应(RT-PCR)和放射免疫方法分别检测20例PDR和10例正常对照玻璃体切除物中MMP-2、MMP-9 mRNA的表达与MMP-2、MMP-9的含量.结果:PDR玻璃体切除物中MMP-2、MMP-9 mRNA与MMP-2、MMP-9的含量均高于正常对照(P<0.05).结论:MMP-2和MMP-9可能在PDR的发生、发展中起重要作用.

  6. 基质金属蛋白酶MMP-2、MMP-9及其抑制因子TIMP-1、TIMP-2在子宫内膜异位症血清中的表达及临床意义%Expression and significance of MMP-2, MMP-9 and TIMP-1, TIMP-2 in endometriosis in serum

    Institute of Scientific and Technical Information of China (English)

    陶晓薇; 顾丽娟

    2014-01-01

    目的 探讨基质金属蛋白酶MMP-2、MMP-9及其抑制因子TIMP-1、TIMP-2在子宫内膜异位症(EMs)血清中的表达及临床意义.方法 采用双抗体夹心酶联免疫吸附法(ELISA)检测55例EMs患者和30例对照组血清中MMP-2,MMP-9、TIMP-1和TIMP-2水平.结果 EMs组血清中MMP-2和MMP-9水平显著高于对照组,TIMP-1和TIMP-2水平显著低于对照组(P<0.05).IⅢ-Ⅳ期血清中MMP-2和MMP-9水平显著高于I-Ⅱ期和对照组,TIMP-1和TIMP-2水平显著低于Ⅰ-Ⅱ期和对照组(P<0.05).结论 MMP-2、MMP-9与EMs发生和发展相关,TIMP-1、TIMP-2对MMP-2、MMP-9水平调节有重要作用.

  7. Expression of CCR7, L-selectin, CD44v6 and MMP9 in colorectal cancer and their relative with lymphatic metastatic%大肠癌中CCR7、L-selectin、CD44v6和MMP9表达及其与淋巴转移的关系

    Institute of Scientific and Technical Information of China (English)

    武欣; 李坤; 张凡; 刘军超; 林媛媛; 金春亭

    2013-01-01

    目的 探讨CC趋化因子受体7(CCR7)、L-selectin、CD44v6和MMP9在大肠癌组织中的表达及其与大肠癌淋巴转移的关系.方法 采用免疫组化PV 9000两步法检测104例大肠癌组织(大肠癌组)、55例癌旁正常组织(癌旁组)和34例转移灶组织(转移组)中CCR7和L-selectin、CD44v6和MMP9的表达.结果 大肠癌组、转移组中CCR7、L-selectin、CD44v6和MMP9阳性率明显高于癌旁组(P<0.05),有淋巴结转移者明显高于无转移者(P<0.05);CCR7与L-selectin、MMP9表达呈正相关(P<0.05);CD44v6与L-selectin、MMP9表达相关;L-selectin与MMP9的表达呈正相关.结论 CCR7、L-selectin、CD44v6和MMP9在大肠癌中的表达与大肠癌的发生、淋巴转移有关,它们可能共同参与了大肠癌发生及淋巴结转移过程.%Purpose To investigate the expression of chemokine receptor 7 ( CCR7 ), adhesion molecule L-selectin, CD44v6 and MMP9 in human colorectal carcinoma, and analyze their correlation with lymph node metastasis. Methods The expression of CCR7, L-selectin, CD44v6 and MMP9 were tested by immunohistochemical method in 104 cases of colorectal carcinoma specimens ( colorectal carcinoma group ), 55 cases of normal intestinal mucosa adjacent to carcinoma ( adjacent group ) and 34 cases of metastatic tumor tissue ( metastasis group). Results The positive rate of CCR7, L-selectin, CD44v6 and MMP9 expression in the colorectal carcinoma group and metastatic tumor tissue were significantly higher than that in adjacent group and metastasis group ( P < 0. 05 ). The expression of CCR7, L-selectin, CD44v6 and MMP9 in the tissue with lymph node metastasis was significantly higher than that in the tissue without lymph node metastasis ( P <0. 05 ). There was significantly positive correlation between expression of CCR7 and L-selectin, CCR7 and MMP9, CD44v6 and L-selectin, CD44v6 and MMP9, L-selectin and MMP9 ( P < 0. 05 ). Conclusions The expression of CCR7, L-selectin, CD44v6 and MMP9 are closely

  8. 儿童寻常型银屑病血清中IL-17、TNF-α、MMP-9、TIMP-1的表达%Expression of serum IL-17, TNF-α, MMP-9 and TIMP-1 in children psoriasis vulgaris

    Institute of Scientific and Technical Information of China (English)

    杨瑞海; 牟丽萍

    2015-01-01

    目的:探讨寻常型银屑病患儿血清白细胞介素-17(IL-17)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)的水平。方法32例寻常型银屑病患儿(观察组)和34例健康儿童(对照组)为研究对象,比较两组血清中IL-17、TNF-α、MMP-9、TIMP-1表达水平的差异。结果观察组血清IL-17、TNF-α、MMP-9、TIMP-1水平和MMP-9/TIMP-1比值均较对照组升高,差异均具有统计学意义(P<0.01)。结论IL-17、TNF-α、MMP-9和TIMP-1在儿童寻常型银屑病的发病机制中起着重要作用。%ObjectiveTo investigate level of interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in children psoriasis vulgaris.MethodsA total of 32 children with psoriasis vulgaris (observation group) and 34 healthy children (control group) were taken as study subjects. Differences of expression of serum IL-17, TNF-α, MMP-9 and TIMP-1 were compared between the two groups.ResultsThe observation group had higher serum IL-17, TNF-α, MMP-9, TIMP-1, and ratio of MMP-9/TIMP-1 than the control group, and their differences all had statistical significance (P<0.01).ConclusionIL-17, TNF-α, MMP-9 and TIMP-1 act important roles in pathogenesis of children psoriasis vulgaris.

  9. A Study on the Relationship Between Expression of MMP-2,MMP-9 and Metastasis and Prognosis in Patients with Lung Cancer%MMP-2、MMP-9在肺癌中的表达及其与肺癌转移和预后关系的研究

    Institute of Scientific and Technical Information of China (English)

    薛洋; 周清华; 张尚福; 刘伦旭

    2008-01-01

    目的:探讨非小细胞肺癌(NSCLC)组织中基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶-9(MMP-9)的表达水平与肺癌转移和预后的关系.方法:应用免疫组化(LSAB法)检测了108例非小细胞肺癌和19例肺良性病变中MMP-2、MMP-9的表达水平.结果:(1)肺癌组织中MMP-2、MMP-9的表达水平均显著高于癌旁肺组织和肺良性病变肺组织(P<0.01).(2)伴有淋巴结或/和远外转移的肺癌中MMP-2、MMP-9的表达水平均显著高于不伴有淋巴结或/和远外转移的肺癌(P<0.01或P<0.05).(3)MMP-2、MMP-9在肺鳞癌中的表达水平显著高于在腺癌和腺鳞癌中的表达水平(P<0.01).(4)肺癌组织中MMP-2、MMP-9的表达水平呈显著正相关(P<0.05).(5)多因素COX比例风险模型分析显示:MMP-2、MMP-9的表达水平对于预测肺癌预后具有一定意义.结论:(1)肺癌中MMP-2、MMP-9的表达水平明显升高,且与肺癌的进展和转移有密切关系.(2)肺癌组织中MMP-2、MMP-9的表达水平呈显著正相关(P<0.05).(3)检测肺癌中MMP-2、MMP-9的表达水平有助于预测肺癌的预后,指导肺癌的多学科综合治疗.

  10. The expressions of MMP-2,MMP-7,MMP-9 and EMMPRIN in human colorectal carcinoma and its significance%结、直肠癌中MMP-2、MMP-7、MMP-9与EMMPRIN 的表达及意义

    Institute of Scientific and Technical Information of China (English)

    凌林; 胡郁之; 孙礼侠; 刘昌阔; 刘志刚

    2015-01-01

    目的::探讨基质金属蛋白酶( MMP)-2、MMP-7、MMP-9和基质金属蛋白酶诱导因子( EMMPRIN)在结、直肠癌中的表达以及在结、直肠癌发展过程中的作用。方法:采用免疫组织化学法检测100例结、直肠癌组织中MMP-2、MMP-7、MMP-9和EMMPRIN的表达。结果:MMP-2、MMP-7、MMP-9和EMMPRIN在结、直肠癌组织中的表达在结、直肠癌的浸润深度、Dukes分期和有无淋巴结转移间差异均有统计学意义(P<0.01);EMMPRIN分别与MMP-2、MMP-7、MMP-9蛋白在结、直肠癌组织中的表达呈正相关关系(P<0.01)。结论:MMP-2、MMP-7、MMP-9和EMMPRIN在结、直肠癌的演进过程中可能具有一定的协同作用。%Objective:To investigate the expressions of matrix metalloproteinases-2,7 and 9(MMP-2,MMP-7 and MMP-9) and extracellular matrix metalloproteinase inducer ( EMMPRIN ) and their roles in the development process of colorectal carcinoma. Methods:The protein expressions of MMP-2,MMP-7,MMP-9 and EMMPRIN in 100 colorectal carcinoma tissue samples were detected by immunohistochemical method. Results:The differences of the expressions rates of MMP-2, MMP-7, MMP-9 and EMMPRIN in colorectal carcinoma tissue samples with different invasion depth,Dukes stage and lymph node metastasis were statistically significant (P<0. 05). The expressions between EMMPRIN and MMP-2,MMP-7 and MMP-9 in colorectal carcinoma tissue were significant positive correlation,respectively(P<0. 01). Conclusions:The expressions of MMP-2,MMP-7,MMP-9 and EMMPRIN have synergetic effects in the development of colorectal carcinoma.

  11. 结核性脑膜炎患儿脑脊液中IL-17和MMP-9的水平及意义%Level of IL-17 and MMP-9 in cerebrospinal fluid of children with tuberculous meningitis and its significance

    Institute of Scientific and Technical Information of China (English)

    张传新; 贾国存; 陈国洪; 王莉

    2013-01-01

    Objective To detect the levels of IL-17 and MMP-9 in cerebrospinal fluid of children with tuberculous meningitis,and to study their role in the diagnosis of tuberculous meningitis.Methods The 15 cases of children with tuberculous meningitis (TBM),20 cases of children with viral encephalitis (VM) and 18 cases of children without central nervous system infections,were choosed as the TBM group,the VM group and the control group.The levels of IL-17 and MMP-9 in cerebrospinal fluid were detected by ELISA method.Results The levels of IL-17 and MMP-9 in cerebrospinal fluid in TBM group increased significantly.Compared with other two groups,respectively,the differences were significant (P <0.01).Conclusions The levels of IL-17 and MMP-9 in cerebrospinal fluid of patients with tuberculous meningitis were all highly increased,suggesting they might be involved in the pathological process of tuberculous meningitis.The levels of IL-17 and MMP-9 in cerebrospinal fluid can help identification of tuberculous meningitis with viral meningitis.%目的 检测结核性脑膜炎患儿脑脊液中白细胞介素-17 (IL-17)和金属基质蛋白酶-9(MMP-9)的水平,探讨其在结核性脑膜炎发病及诊断中的作用.方法 将15例结核性脑膜炎(TBM)、20例病毒性脑炎(VM)及18例非中枢神经系统感染儿童,分列为TBM组、VM组和对照组.应用ELISA法测定3组儿童脑脊液中IL-17和MMP-9的水平.结果 TBM组脑脊液中IL-17和MMP-9水平明显升高,与其他两组相比较,差异均有统计学意义(P<0.0l).结论 IL-17和MMP-9在结核性脑膜炎患儿脑脊液中均显著升高,提示它们可能参与了结核性脑膜炎的病理过程.检测脑炎患儿脑脊液中IL-17、MMP-9水平,有助于结核性脑膜炎与病毒性脑膜炎的临床鉴别.

  12. 乳腺癌组织中 VEGF-D、MMP-2及 MMP-9的表达及其临床意义%The Expressions and Clinical Significance of Matrix Metalloproteinases 2(MMP-2),Ma-trix Metalloproteinases 9 (MMP-9) and Vascular Endothelial Growth Factor-D (VEGF-D) in Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    张阿娜

    2016-01-01

    目的:探讨乳腺癌组织中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)和血管内皮生长因子D( VEGF-D)表达的临床意义。方法采用免疫组化法,对60例乳腺癌组织及60例正常组织中 MMP-2、MMP-9及VEGF-D表达情况进行检测。结果60例乳腺癌组织中,MMP-2、MMP-9阳性表达率分别为61.67%、56.67%,VEGF-D阳性表达率为61.67%。 MMP-2、MMP-9及VEGF-D阳性表达率Ⅲ~Ⅳ期者显著高于Ⅰ~Ⅱ期者;低分化者显著高于高、中分化者;有淋巴结转移者显著高于无淋巴结转移者;且MMP-2与VEGF-D表达,MMP-9与VEGF-D表达均呈正相关性。结论低分化、Ⅲ~Ⅳ期乳腺癌患者高表达MMP-2、MMP-9与VEGF-D,MMPs与VEGF-D表达呈正相关性,可通过阻断VEGF-D及MMPs活性控制、治疗乳腺癌。%Objective To explore the expressions of matrix metalloproteinases 2 ( MMP-2 ) ,matrix metalloproteinases 9 (MMP-9) and vascular endothelial growth factor-D(VEGF-D)and their significance in breast cancer tissues.Methods The ex-pressions of MMP-2,MMP-9 and VEGF-D in 60 cases of breast cancer tissues and 60 cases of normal esophageal tissues were de-tected by immunohistochemistry.Results The expression rates of MMP-2,MMP-9 and VEGF-D in breast cancer tissues were 61.67%,56.67%and 61.67%.The expression rates of MMP-2,MMP-9 and VEGF-D in grade Ⅲ-Ⅳ were significantly higher than that of gradeⅠ-Ⅱ.The expression rates of MMP-2,MMP-9 and VEGF-D in patients with poor differentiation were signifi-cantly higher than that with well-mediate differentiation.The expression rates of MMP-2,MMP-9 and VEGF-D in patients with lymph node metastasis were significantly higher than that without lymph node metastasis.MMP-2 and VEGF-D expression were positively correlated.MMP-9 and VEGF-D expression were also positively correlated.Conclusion The expression rates of MMP-2,MMP-9 and VEGF-D are closely related to poor differentiation

  13. Expression of COX-2 and MMP-9 in Patients with EMP in Pre-and Post-menopausal Women%COX-2和MMP-9在绝经前后子宫内膜息肉中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    薛翔; 郭维; 公丕军

    2012-01-01

    Objective To investigate the expression of Cyctooxygenase - 2 ( COX - 2 ) , matrix metalloproteinase- 9( MMP -9) in patients with endometrial polyps( EMP) in pre - and post - menopausal women and their relationship, and to investigate the pathogenesis of EMP. Methods 150 cases with EMP (45 from pre -menopausal women and the other 45 from post - menopausal women) and 60 cases with normal endometrium (30 were proliferative phase endometrium and the other 30 were atrophic endometrium) were collected. Immunohistochemical SP method was used to detect the expression of COX - 2 and MMP - 9 in each tissue. Results 1. In Premenopausal group: Expression of COX - 2 and MMP - 9 in epithelial cells and stroma of EMP were all significantly higher than those in the normal proliferative phase endometrium (P 0. 05 ) . 4. There was a significantly positive correlation between expression of COX -2 and MMP -9(r =0. 6135 ,P < 0.01). Conclusion The expression of COX - 2 is closely associated with MMP -9. Overexpression of COX -2 and MMP -9 in the EMP suggested that COX -2 and MMP -9 may play a role in development of EMP. The pathogenesis of pre - and postmenopausal endometrial polyps may be difference, which may be related to estrogen levels.%目的 研究绝经前、后子宫内膜息肉(EMP)中环氧合酶-2(COX-2)、基质金属蛋白酶-9(MMP-9)的表达及二者的相关性,为研究EMP形成机理提供线索.方法 选取存档石蜡标本共150例,其中绝经前、后EMP各45例,绝经前正常增生期子宫内膜和绝经后正常萎缩型子宫内膜各30例,用免疫组化SP法检测各组COX-2、MMP-9的表达情况,并分析两指标在EMP组织中的表达及相关性.结果 绝经前组COX-2、MMP-9在EMP腺体和间质的表达均显著高于二者在正常增生期子宫内膜中的表达(P<0.05).绝经后组COX-2、MMP-9在EMP间质和腺体中的表达均高于二者在绝经后正常萎缩型子宫内膜中的表达(P<0.05).COX-2在绝经前、后EMP腺体中

  14. Co-expression of MMP-9/IgA and TIMP-1/IgA in renal tissue of IgA nephropathy and its significance%MMP-9/IgA和TIMP-1/IgA在IgA肾病患者肾组织中的共表达及意义

    Institute of Scientific and Technical Information of China (English)

    师锁柱; 张雪光; 陈香美

    2011-01-01

    目的 观察基质金属蛋白酶-9(MMP-9)及其组织抑制因子-1(TIMP-1)和免疫球蛋白A(IgA)在IgA肾病不同病变肾小球内共表达情况,探讨IgA沉积在IgA肾病进展中的作用.方法 采用石蜡切片免疫荧光双标记技术,对56例不同病理分级IgA肾病(Lee氏分级Ⅰ-Ⅴ级)患者肾组织中MMP-9/IgA、TIMP-1/IgA共表达变化进行检测.结果 在Lee氏分级Ⅰ-Ⅱ级肾小球中TIMP-1/IgA有少量表达,MMP-9/IgA表达最多.Lee氏分级Ⅲ级肾小球中TIMP-1/IgA表达增多,MMP-9/IgA表达减少,在Lee氏分级Ⅳ-Ⅴ级重度系膜病变肾小球内TIMP-1/IgA表达最多,MMP-9/IgA有少量表达,而在硬化肾小球内两者表达最少.结论 在IgA肾病进展过程中随着肾小球内IgA沉积增多,肾小球内TIMP-1表达逐渐增高,MMP-9表达逐渐减少,提示IgA沉积引起的MMP-9/TIMP-1失衡参与了IgA肾病肾小球硬化过程.%Objective To study the role of immunoglobulin A(IgA) deposition in the progress of IgA nephropathy by observing the co-expression of matrix metalloproteinase-9(MMP-9), its tissue inhibitor-l(TIMP-l) and IgA in IgA nephropathy patients with variant glomerular lesions. Methods Co-expression of MMP-9/IgA and TTMP-l/IgA in renal tissues from 56 patients with IgA nephropathy(Lee levels I-V) was detected with immunofluorescence double-staining. Results The TIMP-1/IgA was lowly expressed while the MMP-9/IgA was highly expressed in glomeruli of patients with IgA nephropathy(Lee levels I-II). The expression level of TIMP-1/IgA was higher while that of MMP-9/IgA was lower in glomeruli of patients with IgA neprhropathy(Lee level HI). The expression level of TIMP-1/IgA was the highest while that of MMP-9/IgA was lower in glomeruli of patients with IgA nephropathy(Lee level IV-V) and the lowest in sclerotic glomeruli of patients with IgA nephropathy. Conclusion The IgA deposition and TTMP-1 expression are increased while the MMP-9 expression is decreased during the progress of Ig

  15. MCP-1 Stimulates MMP-9 Expression via ERK 1/2 and p38 MAPK Signaling Pathways in Human Aortic Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Ci-Qiu Yang

    2014-07-01

    Full Text Available Objective: We investigated the molecular mechanism underlying the role of monocyte chemoattractant protein-1 (MCP-1 in the formation and development of human abdominal aortic aneurysm (AAA. Methods: We examined protein expression profiles using a protein array and found that MCP-1 was the most highly expressed protein in AAA tissues compared with normal aortas. To investigate the potential mechanism of MCP-1 involvement in the pathogenesis of AAA, we treated human aortic smooth muscle cells (HASMCs with human recombinant MCP-1. Results: MCP-1 was the most highly expressed protein in AAA tissues compared with normal aorta; matrix metalloproteinase-9 (MMP-9 expression was also significantly increased. Treatment with MCP-1 significantly increased the expression and activation of MMP-9 and activated the three major mitogen activated protein kinases (MAPKs extracellular signal regulated kinase (ERK, c-Jun amino terminal kinase (JNK1/2 and p38 MAPK. Furthermore, MCP-1-induced secretion of MMP-9 was inhibited by U0126 (inhibitor of the ERK 1/2 pathway and SB203580 (inhibitor of the p38 MAPK pathway, but not SP600125 (inhibitor of the JNK1/2 pathway. Conclusion: These data demonstrate that MCP-1 stimulates secretion of MMP-9 directly through the ERK1/2 and p38 MAPK mediated pathways in HASMCs. Thus, inhibition of this molecular mechanism might be a potential therapeutic target in the non-surgical treatment of AAA.

  16. Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Young-Rae Lee

    2013-04-01

    Full Text Available Sulforaphane [1-isothiocyanato-4-(methylsulfinyl-butane] is anisothiocyanate found in some cruciferous vegetables, especiallybroccoli. Sulforaphane has been shown to displayanti-cancer properties against various cancer cell lines. Matrixmetalloproteinase-9 (MMP-9, which degrades the extracellularmatrix (ECM, plays an important role in cancer cell invasion.In this study, we investigated the effect of sulforaphane on12-O-tetradecanoyl phorbol-13-acetate (TPA-induced MMP-9expression and cell invasion in MCF-7 cells. TPA-inducedMMP-9 expression and cell invasion were decreased bysulforaphane treatment. TPA substantially increased NF-κB andAP-1 DNA binding activity. Pre-treatment with sulforaphaneinhibited TPA-stimulated NF-κB binding activity, but not AP-1binding activity. In addition, we found that sulforaphanesuppressed NF-κB activation, by inhibiting phosphorylation ofIκB in TPA-treated MCF-7 cells. In this study, we demonstratedthat the inhibition of TPA-induced MMP-9 expression and cellinvasion by sulforaphane was mediated by the suppression ofthe NF-κB pathway in MCF-7 cells. [BMB Reports 2013; 46(4:201-206

  17. Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma

    NARCIS (Netherlands)

    Sier, C.F.M.; Kubben, F.J.G.M.; Ganesh, S.; Heerding, M.M.; Griffioen, G.; Hanemaaijer, R.; Krieken, J.H.J.M. van; Lamers, C.B.H.W.; Verspaget, H.W.

    1996-01-01

    Proteinases are involved in tumour invasion and metastasis. Several matrix metalloproteinases (MMPs) have been shown to be increased in various human carcinomas. We assessed the levels of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in 50 gastric carcinomas and corresponding mucosa using

  18. Immunohistochemical analysis of MMP-9, MMP-2 and TIMP-1, TIMP-2 expression in the central nervous system following infection with viral and bacterial meningitis.

    Science.gov (United States)

    Sulik, Artur; Chyczewski, Lech

    2008-01-01

    Matrix metalloproteinases (MMPs) are capable of degrading components of the basal lamina of cerebral vessels, thereby disrupting the blood-brain barrier and inducing leukocyte recruitment. This study provides comprehensive information regarding the cell specificity of matrix metalloproteinases (MMP-2, MMP-9) and their binding tissue inhibitors (TIMP-1, TIMP-2) in the central nervous system during viral and bacterial meningitis. Specifically, we evaluated the immunoreactivity of MMPs and TIMPs in various cell types in brain parenchyma and meninges obtained from autopsy tissues. We found that a higher proportion of endothelial cells were positive for MMP-9 during meningitis when compared to controls. In addition, the immunoreactivity of MMP-9 decreased and the immunoreactivity of TIMP-1 increased in astrocytes upon infection. Furthermore, the results of this study revealed that mononuclear cells were highly immunoreactive for TIMP-1, TIMP-2 and MMP-9 during viral meningitis and that the expression of TIMPs in polymorphonuclear cells was even higher during bacterial meningitis. Taken together the results of this study indicated that the central nervous system resident cells and inflammatory infiltrates contribute to MMPs activity and that the expression patterns vary between cell types and in response to viral and bacterial meningitis.

  19. Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells.

    Science.gov (United States)

    Lee, Young-Rae; Noh, Eun-Mi; Han, Ji-Hey; Kim, Jeong-Mi; Hwang, Bo-Mi; Kim, Byeong-Soo; Lee, Sung-Ho; Jung, Sung Hoo; Youn, Hyun Jo; Chung, Eun Yong; Kim, Jong-Suk

    2013-04-01

    Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is an isothiocyanate found in some cruciferous vegetables, especially broccoli. Sulforaphane has been shown to display anti-cancer properties against various cancer cell lines. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in cancer cell invasion. In this study, we investigated the effect of sulforaphane on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. TPA-induced MMP-9 expression and cell invasion were decreased by sulforaphane treatment. TPA substantially increased NF-κB and AP-1 DNA binding activity. Pre-treatment with sulforaphane inhibited TPA-stimulated NF-κB binding activity, but not AP-1 binding activity. In addition, we found that sulforaphane suppressed NF-κB activation, by inhibiting phosphorylation of IκB in TPA-treated MCF-7 cells. In this study, we demonstrated that the inhibition of TPA-induced MMP-9 expression and cell invasion by sulforaphane was mediated by the suppression of the NF-κB pathway in MCF-7 cells.

  20. Immunohistochemical analysis of MMP-9, MMP-2 and TIMP-1, TIMP-2 expression in the central nervous system following infection with viral and bacterial meningitis.

    Directory of Open Access Journals (Sweden)

    Lech Chyczewski

    2009-01-01

    Full Text Available Matrix metalloproteinases (MMPs are capable of degrading components of the basal lamina of cerebral vessels, thereby disrupting the blood-brain barrier and inducing leukocyte recruitment. This study provides comprehensive information regarding the cell specificity of matrix metalloproteinases (MMP-2, MMP-9 and their binding tissue inhibitors (TIMP-1, TIMP-2 in the central nervous system during viral and bacterial meningitis. Specifically, we evaluated the immunoreactivity of MMPs and TIMPs in various cell types in brain parenchyma and meninges obtained from autopsy tissues. We found that a higher proportion of endothelial cells were positive for MMP-9 during meningitis when compared to controls. In addition, the immunoreactivity of MMP-9 decreased and the immunoreactivity of TIMP-1 increased in astrocytes upon infection. Furthermore, the results of this study revealed that mononuclear cells were highly immunoreactive for TIMP-1, TIMP-2 and MMP-9 during viral meningitis and that the expression of TIMPs in polymorphonuclear cells was even higher during bacterial meningitis. Taken together the results of this study indicated that the central nervous system resident cells and inflammatory infiltrates contribute to MMPs activity and that the expression patterns vary between cell types and in response to viral and bacterial meningitis.

  1. Curcumin Alleviates oxLDL Induced MMP-9 and EMMPRIN Expression through the Inhibition of NF-κB and MAPK Pathways in Macrophages

    Science.gov (United States)

    Cao, Jiatian; Ye, Bozhi; Lin, Lu; Tian, Lei; Yang, Hongbo; Wang, Changqian; Huang, Weijian; Huang, Zhouqing

    2017-01-01

    Rupture of vulnerable atherosclerotic plaques is the leading cause of acute myocardial infarction (AMI) and unstable angina pectoris (UA). However, it still lacks an effective therapy to stabilize the vulnerable atherosclerotic plaques. Numerous reports have shown that upregulation of MMP-9 (matrix metalloproteinase-9) and EMMPRIN (extracellular matrix metalloproteinase inducer) in macrophages is involved in the progression and development of vulnerable plaques. Here we evaluated the impact of curcumin on the expression of MMP-9 and EMMPRIN in macrophages. Macrophages were pretreated with curcumin or specific inhibitors (p38 MAPK inhibitor, NF-κB p65 inhibitor) for 1 h, then cells were cultured with oxLDL for indicated time. Real-time PCR and Western blot analysis were used to evaluate the expression of mRNA and proteins. Translocation of NF-κB p65 was detected by using laser confocal microscopy. Here we showed that curcumin attenuated the MMP-9 and EMMPRIN expression in oxLDL stimulated macrophages. Further studies revealed that curcumin inhibited oxLDL induced NF-κB activation and p38 MAPK phosphorylation. These findings illustrated that curcumin can inhibit the expression of EMMPRIN and MMP-9 in oxLDL stimulated macrophages through down regulation of NF-κB and p38 MAPK signaling pathways, which might be the molecular mechanism for the anti-atherosclerotic effect of curcumin. PMID:28261097

  2. Ginseng and Its Active Components Ginsenosides Inhibit Adipogenesis in 3T3-L1 Cells by Regulating MMP-2 and MMP-9

    Directory of Open Access Journals (Sweden)

    Jaeho Oh

    2012-01-01

    Full Text Available The growth and development of adipose tissue are believed to require adipogenesis, angiogenesis, and extracellular matrix remodeling. As our previous study revealed that ginseng reduces adipose tissue mass in part by decreasing matrix metalloproteinase (MMP activity in obese mice, we hypothesized that adipogenesis can be inhibited by ginseng and its active components ginsenosides (GSs. Treatment of 3T3-L1 adipocytes with Korean red ginseng extract (GE inhibited lipid accumulation and the expression of adipocyte-specific genes (PPARγ, C/EBPα, aP2, and leptin. GE decreased both the mRNA levels and activity of MMP-2 and MMP-9 in 3T3-L1 cells. These effects were further inhibited by total GSs (TGSs and individual GSs. TGSs and individual GSs also significantly decreased MMP-2 and MMP-9 reporter gene activities in the presence of phorbol 12-myristate 13-acetate (PMA, the MMP inducer. Among the GSs, Rb1 most effectively inhibited MMP activity. In addition, PMA treatment attenuated the inhibitory actions of GE and GSs on adipogenesis. Moreover, GE and GSs reduced the expression of NF-κB and AP-1, the transcription factors of MMP-2 and MMP-9. These results demonstrate that ginseng, in particular GSs, effectively inhibits adipogenesis and that this process may be mediated in part through the suppression of MMP-2 and MMP-9. Thus, ginseng and GSs likely have therapeutic potential for controlling adipogenesis.

  3. pERK和MMP-9在甲状腺乳头状癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    董郁红; 赵小玲; 董久玲; 刘宏侠

    2012-01-01

    目的 探讨pERK和MMP-9蛋白在甲状腺乳头状癌(PTC)中的表达及其临床意义. 方法 收集168例PTC及80例癌旁正常甲状腺组织石蜡标本,采用免疫组织化学Envision法检测pERK和MMP-9蛋白的表达情况,分析其表达与PTC临床病理指标之间的关系. 结果 pERK和MMP-9蛋白在PTC组织中的阳性表达率均明显高于癌旁正常甲状腺组织(P<0.01).在PTC组织中,pERK的阳性表达与UICC分期、颈部淋巴结转移以及包膜浸润密切相关(P<0.01),而与年龄、性别、肿瘤大小无关(P>0.05);MMP-9的阳性表达与肿瘤大小、UICC分期、颈部淋巴结转移以及包膜浸润密切相关(P<0.01),而与年龄、性别无关(P>0.05).Spearman等级相关分析pERK与MMP-9在PTC组织中表达呈正相关(r=0.578,P<0.01). 结论 pERK和MMP-9蛋白在PTC中均呈高表达,预示PTC的侵袭转移能力强和预后不良;在PTC浸润、转移等演进过程中,MMP9的作用方式可能与ERK信号途径存在一定关系.

  4. Expression of MMP-9 and VEGF in Human Cervical Cancer Cell Line CaSki after Carbon Dioxide Treatment%CO2气腹对人宫颈癌CaSki细胞MMP-9和VEGF表达的影响

    Institute of Scientific and Technical Information of China (English)

    苏东方; 李莉

    2014-01-01

    目的 探讨腹腔镜二氧化碳(CO2)气腹对人宫颈癌CaSki细胞株基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响.方法 建立腹腔镜CO2气腹体外模型,将CaSki细胞株分别置于0、7和14mmHg的CO2气腹环境下培养1、2、4和8h.采用RT-PCR和Western blot法分别检测处理后各组CaSki细胞株中MMP-9和VEGF表达情况.结果 RT-PCR和Western blot结果显示,与0 mmHg CO2气腹组相比,7和14 mmHg CO2气腹组CaSki细胞株MMP-9和VEGF的mRNA和蛋白表达显著增加(P<0.05),且随着处理时间的延长MMP-9和VEGF的表达呈上升趋势(P<0.05),处理4h时MMP-9和VEGF的表达量达到高峰;在同一时间点时,7mmHg CO2气腹组的MMP-9和VEGF表达量最高(P<0.05).结论 在一定压力和作用时间范围内,CO2气腹可能是通过上调MMP-9和VEGF的表达,进而促进肿瘤生长.

  5. Indacaterol inhibits tumor cell invasiveness and MMP-9 expression by suppressing IKK/NF-κB activation.

    Science.gov (United States)

    Lee, Su Ui; Ahn, Kyung-Seop; Sung, Min Hee; Park, Ji-Won; Ryu, Hyung Won; Lee, Hyun-Jun; Hong, Sung-Tae; Oh, Sei-Ryang

    2014-08-01

    The β2 adrenergic receptor (ADRB2) is a G protein-coupled transmembrane receptor expressed in the human respiratory tract and widely recognized as a pharmacological target for treatments of asthma and chronic obstructive pulmonary disorder (COPD). Although a number of ADRB2 agonists have been developed for use in asthma therapy, indacaterol is the only ultra-long-acting inhaled β2-agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients. The precise molecular mechanism underlying the pharmacological effect of indacaterol, however, remains unclear. Here, we show that β-arrestin-2 mediates the internalization of ADRB2 following indacaterol treatment. Moreover, we demonstrate that indacaterol significantly inhibits tumor necrosis factor-α (TNF-α)-induced NF-κB activity by reducing levels of both phosphorylated-IKK and -IκBα, thereby decreasing NF-κB nuclear translocation and the expression of MMP-9, an NF-κB target gene. Subsequently, we show that indacaterol significantly inhibits TNF-α/NF-κB-induced cell invasiveness and migration in a human cancer cell line. In conclusion, we propose that indacaterol may inhibit NF-κB activity in a β-arrestin2-dependent manner, preventing further lung damage and improving lung function in COPD patients.

  6. Activity of MMP-9 after repair of abdominal wall defects with acellular and crosslinked bovine pericardium in rabbit.

    Science.gov (United States)

    Singh, Himani; Kumar, Naveen; Sharma, A K; Kataria, Meena; Munjal, Ashok; Kumar, Amit; Dewangan, Rukmani; Kumar, Vineet; Devarathnam, J; Kumar, Sachin

    2014-02-01

    This study was undertaken for the identification of matrix metalloproteinases (MMPs) in extracts obtained from native, acellular and crosslinked bovine pericardium (in vitro), as well as in the plasma after implantation of these biomaterials in rabbits (in vivo). Native pericardium (NP) expressed a 72 kDa (MMP-2) band; whereas, in acellular pericardium (AP) two bands (10 kDa and 92 kDa) of MMPs were observed of which, 92 kDa band was very faint. AP crosslinked with glutaraldehyde did not show any gelatinase activity and thus reflects the creation of new additional chemical bonds between the collagen molecules which has been effectively removed. Gelatin zymography showed only one major band of 92 kDa in all the implanted and untreated rabbit plasma, but the relative amount of 92 kDa was 1-2 times higher in acellular bovine pericardium implanted rabbits as compared to crosslinked and native groups. In NP group, the 92 kDa band was the dullest among the three groups. This indicated that the level of MMP-9 corresponds to the degree of collagen degradation. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  7. Isoproterenol disperses distribution of NADPH oxidase, MMP-9, and pPKCε in the heart, which are mitigated by endothelin receptor antagonist CPU0213

    Institute of Scientific and Technical Information of China (English)

    Yusi CHENG; De-zai DAI; Yin DAI

    2009-01-01

    Aim: Spatial dispersion of bioactive substances in the myocardium could serve as pathological basis for arrhythmogenesis and cardiac impairment by β-adrenoceptor stimulation. We hypothesized that dispersed NADPH oxidase, protein kinase Cε (PKCε), early response gene (ERG), and matrix metalloproteinase 9 (MMP-9) across the heart by isoproterenol (ISO) medication might be mediated by the endothelin (ET) - ROS pathway. We aimed to verify if ISO induced spatially heterogeneous distribution of pPKCε, NAPDH oxidase, MMP-9 and ERG could be mitigated by either an ET receptor antagonist CPU0213 or iNOS inhibitor aminoguanidine.Methods: Rats were treated with ISO (1 mg/kg sc) for 10 days, and drug interventions (mg/kg) either CPU0213 (30 sc) or aminoguani-dine (100 ip) were administered on days 8-10. Expression of NADPH oxidase, MMP-9, ERG, and PKCε in the left and right ventricle (LV, RV) and septum (S) were measured separately.Results: Ventricular hypertrophy was found in the LV, S, and RV, in association with dispersed QTc and oxidative stress in ISO-treated rats. mRNA and protein expression of MMP-9, PKCε, NADPH oxidase and ERG in the LV, S, and RV were obviously dispersed, with aug-mented expression mainly in the LV and S. Dispersed parameters were re-harmonized by either CPU0213, or aminoguanidine. Conclusion: We found at the first time that ISO-induced dispersed distribution of pPKCε, NADPH oxidase, MMP-9, and ERG in the LV, S,and RV of the heart, which were suppressed by either CPU0213 or aminoguanidine. It indicates that the ET-ROS pathway plays a role in the dispersed distribution of bioactive substances following sustained β-receptor stimulation.

  8. Effects of Zhichuan decoction on MMP-9,TIMP-1 during airway remodeling in asthmatic rats%止喘汤对哮喘大鼠模型气道重构中MMP-9、TIMP-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    霍博雅; 张占锋

    2011-01-01

    Objective:To investigate the effects of Traditional Chinese Medicine(TCM) on airway remodeling and the expression of MM P-9 and TIMP-1 in asthmatic rats. Methods: Fifty Sprague-Dawley rats were randomly divided into five groups equally:normal control group,asthmatic group,budesonide aerosol group,scutellaria baicalensis group and Zhichuan decoction group. The model of asthma was established by OVA ( ovalbumin ) sensitizing and challenging; some lung tissues were sliced and stained with HE and morphological indicators of airway were measured by image analysis, the other lung tissues were sliced and stained with Immunohistochemistry and the expression of MMP-9 、TIMP-1 and collagen type IV was observed. Results: Compared with normal controls, the thickness of airway wall in asthmatic models was significantly increased,and the expression of MMP-9 and TIMP-1 was also increased significantly ( P < 0. 01). After intervention with TCM and budesonide aerosol, compared with asthmatic models, the thickness of airway became thinner significantly, meanwhile,the expression of MMP-9 and TIMP-1 was significantly decreased(P < 0. 01 ) ; then compared the two TCM, pulmonary fibrosis of intervention with compound medical herbs was lighter than intervention with the single ( P < 0. 05 ). Airway wall thickness and collagen type IV were associated with MMP-1、 TIMP-1 and MMP-9/TIMP-1. Conclusions: The TCM could decrease the deposition of collagen type IV and reduce the airway thickness by regulating MMP-9 and TIMP-1 levels and influencing the balance between MMP-9 and TIMP-1, the compound based on asthmatic basic pathogenesis of TCM is superior to single herbs.%目的:现察中药止喘汤对哮喘大鼠气道重构的干预,并探讨其对基质金属蛋白酶-9(MMP-9)及金属蛋白酶抑制剂-1(TIMP-1)表达的影响.方法:50只Sprague-Dawley(SD)大鼠随机分为正常组、哮喘组、布地奈德(BUD)组、黄芩组及止喘汤组5组.采用卵清白蛋白(OVA)致敏加激

  9. Association of TNF-α upregulation of MMP-9 activation in monocyte-derived macrophages with progression of joint damage in patients with rheumatoid arthritis%TNF-α上调单核巨噬细胞MMP-9的活性与类风湿关节炎关节破坏的关系

    Institute of Scientific and Technical Information of China (English)

    谢建民; 王好问; 陆才生

    2009-01-01

    目的:探讨TNF-α对单核巨噬细胞基质金属蛋白酶9(MMP-9)的表达与酶活性的影响以及与类风湿关节炎患者关节破坏的关系.方法:用双抗体夹心ELISA法检测类风湿关节炎患者组(RA)和对照组血清和关节滑液中TNF-α、MMP-9的含量,观察MMP-9与X线表现积分(Larsen)的关系.体外将佛波酯(TPA)和不同浓度(0、1、10、20 μg/L)TNF-α共同孵育THP-1细胞24 h后,运用Western blotting方法检测MMP-9蛋白的表达,明胶酶谱法检测MMP-9活性,侵蚀小室法观察分化前后THP-1细胞的侵蚀力.结果:RA患者组血清和关节滑液中TNF-α、MMP-9的水平明显高于对照组(P<0 05),且血清和滑液MMP-9与Larsen积分显著相关(r=0 37和r=0 32,P<0 01);体外细胞实验中,TNF-α上调分化的THP-1中MMP-9的表达和酶活性,并且增强分化的THP-1细胞的侵蚀性,并与TNF-α呈浓度依赖性.结论:TNF-α上调单核巨噬细胞MMP-9表达及活化,增强了炎症细胞的侵蚀力,可能在RA关节破坏机制中起着重要的作用.

  10. 苦参碱对体外培养人增生性瘢痕成纤维细胞 MMP-1、MMP-9表达的影响%Effects of Matrine on Expressions of MMP-1,MMP-9 in Human Hypertropic Scar Fibroblasts in vitro

    Institute of Scientific and Technical Information of China (English)

    陈小婷; 欧斌贤; 唐屈; 黄积荣; 刘达恩; 农庆文

    2014-01-01

    Objective To study the effects of matrine on the expressions of matrix metalloproteinase (MMP)-1, MMP-9 in human hypertropic scar fibroblasts ( HSFb) in vitro.Methods HSFb was cultured in vitro by being treated with different concentrations of matrine[0 mmol/L(control group),2.5 mmol/L,5.0 mmol/L,10.0 mmol/L].Enzyme-linked immunoadsorbent assay(ELISA) was used to detect the expressions of MMP-1,MMP-9 in the treated supernatants.Results The expression levels of MMP-1,MMP-9 in groups of different concentrations of matrine were higher than those in the control group 24 or 48 hours after matrine treatment(P<0.05),the expression levels of MMP-1,MMP-9 in the 5.0 mmol/L matrine group were higher than those in the 2.5,10.0 mmol/L matrine groups ( P<0.05).Conclusion Matrine can increase the expression of MMP-1,MMP-9.It can be applied to hyperplastic scar prevention and treatment .%目的:探讨苦参碱对体外培养人增生性瘢痕成纤维细胞( HSFb )基质金属蛋白酶( MMP-1、MMP-9)表达的影响。方法将浓度分别为0 mmol/L(对照组)、2.5 mmol/L、5.0 mmol/L、10.0 mmol/L苦参碱作用于体外培养人HSFb,采用酶联免疫吸附试验检测加药后上清液中MMP-1、MMP-9表达量。结果苦参碱作用24 h、48 h时各浓度组MMP-1、MMP-9的表达量均高于对照组(P<0.05),5.0 mmol/L组表达量明显高于2.5 mmol/L组、10.0 mmol/L组( P<0.05)。结论苦参碱可增加HSFb MMP-1、MMP-9的表达,抗瘢痕作用好,在增生性瘢痕防治上具有一定的应用前景。

  11. 蝎毒多肽提取物抑制DU-145细胞COX-2和 MMP-9表达的研究%Polypeptide extract from scorpion venom (PESV) downregulates the expression of COX-2 and MMP-9 in DU-145 cell lines

    Institute of Scientific and Technical Information of China (English)

    张月英; 张维东; 贾青; 王兆朋; 黄山英; 宋守琴; 王朝霞

    2006-01-01

    目的:研究蝎毒多肽提取物(peptide extract from scorpion venom, PESV)对雄激素非依赖性人前列腺癌细胞株DU-145COX-2和MMP-9表达的影响,进一步探讨其抗血管生成的分子机制,为抗前列腺癌骨转移提供有效的治疗手段.方法:采用免疫组只化学方法检测PESV对COX-2、MMP-9蛋白表达的影响,应用RT-PCR检测PESV对MMP-9在mRNA水平表达的影响.结果:蝎毒多肽提取物(40μg/mL)作用于前列腺癌细胞后,COX-2、MMP-9蛋白表达水平明显下调(P<0.05),进一步检测发现MMP-9在mRNA水平亦明显下降(P<0.05).结论:蝎毒多肽提取物(PESV)通过抑制前列腺癌细胞血管生成因子COX-2的表达而发挥其抗血管生成作用,具有临床应用价值.

  12. Clinical significance of TIMP-1, MMP-2 and MMP-9's expression in colorectal carcinoma%TIMP-1、MMP-2、MMP-9在大肠癌组织中表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    秦冰; 瞿峰

    2008-01-01

    目的 研究TIMP-1、MMP-2和MMP-9在大肠癌组织中表达的临床意义.方法 采用免疫组化SP法检测50例大肠癌、10例正常大肠黏膜组织中TIMP-1、MMP-2和MMP-9的表达.结果 TIMP-1、MMP-2、MMP-9在正常组织中的表达均较低,而它们在大肠癌组织中阳性率均较高(P<0.05).结论 TIMP-1、MMP-2、MMP-9与大肠癌临床病理参数有关系.TIMP-1、MMP-2和MMP-9可能是大肠癌侵袭转移的分子标记物.

  13. 胃癌MMP-2、MMP-9表达及对微血管生成和肿瘤转移的影响%The Effect of the Expressions of MMP-2,MMP-9 on MVD(microvessel density) and Metastasis in Gastric Adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    姜汉国; 唐慰萍; 李飞红; 蔡琼珍

    2003-01-01

    目的探讨胃腺癌基质金属蛋白酶2、9(MMP-2、MMP-9)表达及对微血管生成和转移的影响.方法应用免疫组织化学S-P法,检测87例胃腺癌组织中MMP-2、MMP-9的表达和微血管密度(MVD).结果胃腺癌组织MMP-2和MMP-9的阳性表达率分别为59.8%(52/87)和41.4%(36/87).MMP-2、MMP-9的表达、MVD与淋巴结转移显著相关(P<0.05,P<0.01).MMP-2的阳性表达与胃腺癌病理分期有关.结论MMP-2、MMP-9与肿瘤新生血管的形成及转移密切相关,是判断胃癌转移有价值的指标.

  14. An Explore of MMP-2, MMP-9, VEGF and Survivin in the Diagnosis and Significiace of Malignant Ascites%MMP-2、MMP-9、VEGF和Survivin在恶性腹水中的诊断意义探讨

    Institute of Scientific and Technical Information of China (English)

    张春玲

    2012-01-01

    目的 探讨MMP-2 、MMP-9 、VEGF 和Survivin 对恶性腹水的诊断价值.方法 收集各种类型腹水及腹腔液,采用ELISA 法检测MMP-2 、MMP-9 、VEGF 和Survivin 水平.结果 癌性腹水组MMP-2 、MMP-9 、VEGF 和Survivin 水平明显高于肝硬化腹水组和结核性腹水组(P 均<0.05),而后2 组间MMP-2 、MMP-9 、VEGF 和Survivin 水平比较则均无明显差别(P > 0.05).结论 MMP-2 、MMP-9 、VEGF 和Survivin 对良、恶性腹水的鉴别诊断有重要价值,它们可能在恶性腹水的形成过程中起着重要作用.

  15. Expression of MMP-2, MMP-9 and collagen type IV and their relationship in colorectal carcinomas%MMP-2、 MMP-9与Ⅳ型胶原在大肠癌中的表达及其相关性研究

    Institute of Scientific and Technical Information of China (English)

    吴畏; 何剪太; 阮景德; 王荣兵; 张阳德

    2008-01-01

    目的: 研究大肠癌中MMP-2、 MMP-9与IV型胶原的表达及其相关性.方法: 对30例Dukes'B、 C期大肠癌患者的癌组织和正常组织进行IV型胶原、 MMP-2、 MMP-9的免疫组织化学检测, 并进行相关性分析.结果: IV型胶原在大肠癌组织中的表达明显降低; MMP-2、 MMP-9在大部分正常大肠组织中均未见表达, 仅少数见到有阳性表达, 而在癌组织中表达明显增强.IV型胶原评分与MMP-9表达之间呈负相关.结论: 大肠癌组织中IV型胶原的表达明显降低, MMP-9对大肠癌中IV型胶原的降解起着重要作用.

  16. Expressions and clinical significance of Glypican3,MMP-9 and MMP-14 in primary hepatocellular carcinoma%Glypican3、MMP-9和MMP-14在原发性肝癌中的表达与临床意义

    Institute of Scientific and Technical Information of China (English)

    刘敏; 曾霞; 侯恩存; 王树声

    2014-01-01

    Objective To investigate the expression characteristics of Glypican3 ,MMP-9 and MMP-14 in primary hepatocellular carcinoma ,and to focus on their roles on the development ,progress and metastasis of tumor .Methods 102 cases of primary hepato-cellular carcinoma were taken as the observation group and 80 cases of normal liver tissues as the control group .The expressions of Glypican3 ,MMP-9 and MMP-14 were detected by the immunohistochemistry method and their expression difference in different clinicopathological characteristics and the correlation were investigated .Results The positive rates of Glypican3 ,MMP-9 and MMP-14 expressions in the observation group were significantly higher than those in the control group .The positive rates of Glypi-can3 ,MMP-9 and MMP-14 expressions were closely correlated with the tumor volume ,differentiation degree ,lymph node metasta-sis ,vessel infiltration ,membrane invasion and PCNA expression .The correlation analysis showed that the positive relationships were found between Glypican3 and MMP-9 ,between Glypican3 and MMP-14 and between MMP-9 and MMP-14 in the observation group(r=0 .48 ,P=0 .024 1 ;r=0 .46 ,P=0 .013 2;r=0 .43 .P=0 .031 3) .The survival analysis showed that expressions of Glypi-can3 ,MMP-9 and MMP-14 were correlated with the patient′s prognosis .Conclusion The higher-expressions of Glypican3 ,MMP-9 and MMP-14 may promote the occurrence and development of primary hepatocellular carcinoma .Detecting the postoperative expres-sions of Glypican3 ,MMP-9 and MMP-14 has certqain value to judge the prognosis in primary hepatocellular carcinoma .%目的:探讨原发性肝癌中磷脂酰肌醇蛋白聚糖(Glypican3)、基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶-14(MMP-14)的表达特征,关注其在肿瘤发生、发展和转移中的作用。方法本试验以102例原发性肝癌作为观察组,以80例正常肝组织作为对照组,采用免疫组织化学方法检测两组中Glypican3、MMP

  17. Expression of HIF-1α, TGF-β1, Muc1 and MMP-9 in placenta: preliminary pathophysiological study of preeclampsia

    Institute of Scientific and Technical Information of China (English)

    Lyu Yan-guan; Dai Xiao-nan; Liu Shan; Wei Hong; Gao Chao; Gao Li; Liu Jia-yin; Cui Yu-gui

    2012-01-01

    Objective: To investigate expressions of hypoxia-inducible factors-1α (HIF-1α),transforming growth factor-β1 (TGF-β1),mucinl (Mucl) and matrix metalloproteinase-9 (MMP-9) in the placenta collected from the preeclampsia patients and normal pregnant women,so as to explore the possible pathophysiological mechanism of preeclampsia.Methods: The placenta villus tissues were obtained from 35 preeclampsia women,including 16 mild preeclampsia and 19 severe preeclampsia,and 20 normal pregnant women,within 5 minutes after placental expulsion.Expressions of HIF-1α,TGF-β1,Mucl and MMP-9 were detected by Western blot.Cellular location was observed by immunohistochemistry.Results: (1) HIF-la was mainly located in cytoplasm and nucleus of placental villous syncytiotrophoblast.Expression level of HIF-1α in the severe preeclampsia group was significantly higher than that in the mild group or control group (P<0.01).(2) TGF-β1 was located in the trophoblast cell and exuviates membrane.Expression level of TGF-β1 in the severe and mild preeclampsia groups was significantly higher than that in control group (P<0.05).(3) Mucl was located in trophoblast cell and exuviates membrane.Expression level of MUC1 in the severe preeclampsia group was significantly higher than that in the mild preeclampsia group and control group (P<0.01).(4) MMP-9 was located in the trophoblast cell and villous stroma,exuviates membrane.Expression levels of MMP-9 in the two preeclampsia groups were lower than that in control group (P>0.05).Conclusion: Expressions of HIF-1a,TGF-β1 and Mucl increased in the placenta of preeclampsia group,while MMP-9 decreased.Mucl can be induced and regulated by HIF-1α and TGF-β1.Over-expression of Mucl in placenta can significantly suppress the activation of MMP-9,which may influence the infiltration of trophoblast cells.The increased expression of HIF-1α and TGF-β1 in placenta may induce higher level of Mucl.This study helped us to understand the

  18. Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1

    Directory of Open Access Journals (Sweden)

    Tang Hao

    2005-05-01

    Full Text Available Abstract Background During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process. Results By using PMA-differentiated human monocyte cells line THP-1, we found that CD147 mediated matrix metalloproteinases (MMPs expression of the leukemic THP-1 cells and thus enhanced the invasiveness of THP-1 cells. After 24 hours of PMA-induced monocyte differentiation, the mean fluorescence intensity of CD147 in differentiated THP-1 cells (289.61 ± 31.63 was higher than that of the undifferentiated THP-1 cells (205.1 ± 19.25. There was a significant increase of the levels of proMMP-2, proMMP-9 and their activated forms in the differentiated THP-1 cells. Invasion assays using reconstituted basement membrane showed a good correlation between the invasiveness of THP-1 cells and the production of MMP-2 and MMP-9. The difference in the MMPs expression and the invasive ability was significantly blocked by HAb18G/CD147 antagonistic peptide AP-9. The inhibitory rate of the secretion of proMMP-9 in the undifferentiated THP-1 cells was 45.07%. The inhibitory rate of the secretion of proMMP-9, the activated MMP-9 and proMMP-2 in the differentiated THP-1 cells was 52.90%, 53.79% and 47.80%, respectively. The inhibitory rate of invasive potential in the undifferentiated cells and the differentiated THP-1 cells was 41.82 % and 25.15%, respectively. Conclusion The results suggest that the expression of CD147 is upregulated during the differentiation of monocyte THP-1 cells to macrophage cells, and CD147 induces the secretion and activation of MMP-2 and MMP-9 and enhances the invasive ability of THP-1

  19. MMP8, MMP9 AND TIMP1 LEVELS IN GCF AND GINGIVAL TISSUE OF PATIENTS WITH GINGIVAL OVERGROWTH DURING ORTHODONTIC TREATMENT

    Directory of Open Access Journals (Sweden)

    Petra Surlin

    2012-03-01

    Full Text Available Aim. Periodontal remodellng produced during dental orthodontic treatment represents a series of biologicallyactive substances, part of them playing some role in the initiation and propagation of inflammatory processes. The present study aims at demonstrating the MMP8, MMP9 and TIMP1 levels intervening in tissular periodontal remodeling produced during orthodontic treatments, accompanied by gingival overgrowth, as a reaction of the marginal periodontium to mechanical stress. Materials and Method. Selected for the study were 21 patients – 13 females and 8 males – with ages between 13 and 32 years (17.6±1.3 years affected with dento-maxillary anomalies, who received orthodontic treatment with fixed apparatus. Sampling from the gingival fluid was performed 6 times, namely: 1 hour prior to the application of the orthodontic apparatus, 4 hours after its application, again after 8 and 24 hours and then 1 and, respectively, 2 weeks later. If gingival hypertrophy was installed (HTG, the hypertrophic gingiva was removed, and an immuno-histo-chemical examination was made. The patient was weekly monitorized in the first 6 weeks – during the initial orthodontic treatment, then monthly, samples being taken over from the gingival sulcus on each visit made in the first 6 weeks. Results. MMP-9 immuno-marking was positive both at corione level and in the deep structures of the covering epithelium. The positive cells at MMP-9 evidenced different intensities at the level of each structure forming the gingival mucous membrane. In four of the cases under analysis, disorganization of the normal layering/stratification of the epithelium was evidenced, along with the presence of numerous red cells in the chorione of the mucous membrane. In such cases, immuno-marking to MMP8 showed a normal intensity, even if few positive cells, dispersed among the extravasated red cells could be observed. Immunologically, MMP8 and MMP9 obey the same pattern, registering maximum

  20. Mycobacterium tuberculosis Upregulates TNF-α Expression via TLR2/ERK Signaling and Induces MMP-1 and MMP-9 Production in Human Pleural Mesothelial Cells.

    Directory of Open Access Journals (Sweden)

    Wei-Lin Chen

    Full Text Available Tumor necrosis factor (TNF-α and matrix metalloproteinases (MMPs are elevated in pleural fluids of tuberculous pleuritis (TBP where pleural mesothelial cells (PMCs conduct the first-line defense against Mycobacterium tuberculosis (MTB. However, the clinical implication of TNF-α and MMPs in TBP and the response of PMCs to MTB infection remain unclear.We measured pleural fluid levels of TNF-α and MMPs in patients with TBP (n = 18 or heart failure (n = 18 as controls. Radiological scores for initial effusion amount and residual pleural fibrosis at 6-month follow-up were assessed. In vitro human PMC experiments were performed to assess the effect of heat-killed M. tuberculosis H37Ra (MTBRa on the expression of TNF-α and MMPs.As compared with controls, the effusion levels of TNF-α, MMP-1 and MMP-9 were significantly higher and correlated positively with initial effusion amount in patients with TBP, while TNF-α and MMP-1, but not MMP-9, were positively associated with residual pleural fibrosis of TBP. Moreover, effusion levels of TNF-α had positive correlation with those of MMP-1 and MMP-9 in TBP. In cultured PMCs, MTBRa enhanced TLR2 and TLR4 expression, activated ERK signaling, and upregulated TNF-α mRNA and protein expression. Furthermore, knockdown of TLR2, but not TLR4, significantly inhibited ERK phosphorylation and TNF-α expression. Additionally, both MTBRa and TNF-α markedly induced MMP-1 and MMP-9 synthesis in human PMCs, and TNF-α neutralization substantially reduced the production of MMP-1, but not MMP-9, in response to MTBRa stimulation.MTBRa activates TLR2/ERK signalings to induce TNF-α and elicit MMP-1 and MMP-9 in human PMCs, which are associated with effusion volume and pleural fibrosis and may contribute to pathogenesis of TBP. Further investigation of manipulation of TNF-α and MMP expression in pleural mesothelium may provide new insights into the mechanisms and rational treatment strategies for TBP.

  1. The role of hypoxia inducible factor-1α in the increased MMP-2 and MMP-9 production by human monocytes exposed to nickel nanoparticles

    Science.gov (United States)

    WAN, RONG; MO, YIQUN; CHIEN, SUFAN; LI, YIHUA; LI, YIXIN; TOLLERUD, DAVID J.; ZHANG, QUNWEI

    2016-01-01

    Nickel is an important economic commodity, but it can cause skin sensitization and may cause lung diseases such as lung fibrosis, pneumonitis, bronchial asthma and lung cancer. With development of nanotechnology, nano-sized nickel (Nano-Ni) and nano-sized titanium dioxide (Nano-TiO2) particles have been developed and produced for many years with new formulations and surface properties to meet novel demands. Our previous studies have shown that Nano-Ni instilled into rat lungs caused a greater inflammatory response as compared with standard-sized nickel (5 μm) at equivalent mass concentrations. Nano-Ni caused a persistent high level of inflammation in lungs even at low doses. Recently, several studies have shown that nanoparticles can translocate from the lungs to the circulatory system. To evaluate the potential systemic effects of metal nanoparticles, we compared the effects of Nano-Ni and Nano-TiO2 on matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) gene expression and activity. Our results showed that exposure of human monocyte U937 to Nano-Ni caused dose- and time- dependent increase in MMP-2 and MMP-9 mRNA expression and pro-MMP-2 and pro-MMP-9 activity, but Nano-TiO2 did not. Nano-Ni also caused dose- and time- related increase in tissue inhibitor of metalloproteinases 1 (TIMP-1), but Nano-TiO2 did not. To determine the potential mechanisms involved, we measured the expression of hypoxia inducible factor 1α (HIF-1α) in U937 cells exposed to Nano-Ni and Nano-TiO2. Our results showed that exposure to Nano-Ni caused HIF-1α accumulation in the nucleus. Furthermore, pre-treatment of U937 cells with heat shock protein 90 (Hsp90) inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG), prior to exposure to Nano-Ni significantly abolished Nano-Ni-induced MMP-2 and MMP-9 mRNA upregulation and increased pro-MMP-2 and pro-MMP-9 activity. Our results suggest that HIF-1α accumulation may be involved in the increased MMP-2 and MMP-9 production in U937 cells

  2. MMP-2、MMP-3、MMP-9和 TIMP-1评价膝关节骨性关节炎的临床研究%The value of MMP-2,MMP-3,MMP-9 and TIMP-1 levels in the evaluation of knee joint osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    贺占坤; 沈杰威

    2013-01-01

    目的:研究膝关节骨性关节炎(OA)患者关节液中基质金属蛋白酶(MMP)-2、MMP-3、MMP-9和基质金属蛋白酶抑制剂-1(T IM P-1)4种蛋白水平,并探讨其与关节损伤程度及患者预后的关系。方法52例患者均给予关节镜下清理术联合玻璃酸钠、双醋瑞因的治疗方法,于治疗前后采用 ELISA 检测52例膝关节 OA 患者及10例症状轻、X线等影像阴性者关节液中MMP-2、MMP-3、MMP-9和TIMP-1的含量并进行相关分析,并在关节镜下对膝关节软骨损伤程度进行评价。结果膝关节OA患者关节液中MMP-2、MMP-3、MMP-9和TIMP-1的含量均明显高于对照组(P<0.01)。关节液中MMP-2、MMP-3、MMP-9和TIMP-1的含量与关节软骨损伤程度呈正相关,随着病情的好转,关节液中MMP-2、MMP-3、MMP-9和TIMP-1的含量也随之降低。结论检测关节液中MMP-2、MMP-3、MMP-9和TIMP-1水平对膝关节OA的早期诊断、病情程度判断、预后评价有一定的意义。%Objective To explore the relationship between the level of matrix metallo-proteinase(MMP)-2 ,MMP-3 ,MMP-9 and matrix metallo-proteinase inhibitor-1(TIMP-1) in the synovial fluid of the patients with knee joint osteoarthritis (OA) and the de-gree of articular cartilage injury and prognosis .Methods 52 patients(knee OA group) were given arthroscopic debridement com-bined with sodium hyaluronate ,diacerein .The levels of MMP-2 ,MMP-3 ,MMP-9 and TIMP-1 in synovial fluid were detected in 52 patients with knee OA and 10 normal controls(control group) by enzyme-linked immunosorbent assay .The degree of cartilage inju-ry was assessed with arthroscopy .Results The level of MMP-2 ,MMP-3 ,MMP-9 and TIMP-1 in knee OA group were significantly higher than those of the control group(all P<0 .01) .The levels of MMP-2 ,MMP-3 ,MMP-9 and TIMP-1 in the synovial fluid were positively correlated with the degree of articular cartilage injury ,and the levels of MMP-2 ,MMP-3 ,MMP-9

  3. Expression of MMP-2, MMP-9 and its tissue inhibitors in patients with endometriosis%子宫内膜异位症患者MMP-2、 MMP-9及其组织抑制因子的表达

    Institute of Scientific and Technical Information of China (English)

    潘孝勇; 刘倩如; 郭美丽; 曾松芳

    2016-01-01

    目的 探讨血清和腹腔液中基质金属蛋白酶MP-2、MMP-9及其组织抑制因子TIMP-1、TIMP-2水平与子宫内膜异位症(EMs)发病的关系.方法 收集2014年1月~2015年12月确诊的83例EMs患者和35例对照组血清和腹腔液,用酶联免疫吸附法(ELISA)检测MMP-2、MMP-9、TIMP-1和TIMP-2的浓度.结果 EMs组血清和腹水中MMP-2 和MMP-9度显著高于对照组,TIMP-1和TIMP-2显著低于对照组(P<0.05);Ⅲ-Ⅳ期患者组MMP-2和MMP-9水平显著高于Ⅰ-Ⅱ期组,TIMP-1和TIMP-2水平显著低于Ⅰ-Ⅱ期组(P<0.05).结论 EMs患者MMP-2和MMP-9高表达,TIMP-1和TIMP-2低表达,MMP-2/TIMP-2和MMP-9/TIMP-1的比值增高,使异位内膜组织具有更强的侵袭力,可能在子宫内膜异位症的发生发展中起重要作用.%Objective:To explore the expression and significance of matrix metallopmteinase-2,-9 (MMP-2,MMP-9) and tissue inhibitor metalloproteinase-1,-2 (TIMP-1,TIMP-2) in endometfiosis (EMs) in serum and peritonoeal fluid.Methods:The serum and peritoneal fluid was obtained from 83 cases EMs patients and 35 cases control group from Jan.2014 to Dec.2015.The concentration of MMP-2,MMP-9,TIMP-1 and TIMP-2 was detected by enzyme-linked immunosorbent assay (ELISA) method.Results:The concentration of MMP-2 and MMP-9 in Serum and peritoneal fluid of EMs group is significantly higher than that of the control group,the concentration of TIMP-1 and TIMP-2 in EMs group was significantly lower than that of the control group (P<0.05).The concentration ofMMP-2 and MMP-9 in]Ⅲ-Ⅳ stage of EMs group is significantly higher than that of Ⅰ-Ⅱ stage,the concentration of TIMP-1 and TIMP-2 in]Ⅲ-Ⅳ stage of EMs group is significantly lower than that of Ⅰ-Ⅱ stage (P<0.05).Conclusion:The increased expression of MMP-2,MMP-9 and the decreased expression of TIMP-1,TIMP-2 in EMs patients result the higher ratio of MMP-2/TIMP-2 and MMP-9/TIMP-1.It can make ectopic endometrial tissues have a greater capactity to

  4. Expression of MMP-9 and BAFF in the Labial Gland of Patients with Primary Sj(o)gren's Syndrome%MMP-9、BAFF在原发性干燥综合征患者唇腺组织中表达的相关研究

    Institute of Scientific and Technical Information of China (English)

    侯西倩; 王竺红

    2013-01-01

    目的 探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、B细胞激活因子(B cell activating factor of the tumor necrosis factor family,BAFF)在原发性干燥综合征(PSS)发病过程中的作用和意义.方法 采用免疫组化SP法检测50例PSS患者及30例正常对照组唇腺组织中MMP-9、BAFF的表达情况.结果 50例PSS患者唇腺组织中MMP-9均阳性高表达,其表达的面积(14382.38±657.39 )μm2、累积光密度(2705.46±868.76)均高于正常对照组(8445.10±361.84)μm2、(1114.26±570.82),且随着淋巴细胞浸润等级的增加,MMP-9表达增强,差异有统计学意义(P<0.05);50例PSS组患者唇腺组织中BAFF均阳性表达,其表达的面积(13586.72±1569.45)μm2、累积光密度(2073.57±850.73)均高于正常对照组(7116.83±338.19)μm2、(850.73±120.31),且随着淋巴细胞浸润等级的增加,BAFF表达增强(P<0.05);PSS组患者唇腺组织中MMP-9与BAFF的表达呈正相关(P<0.05).结论 MMP-9、BAFF的异常表达与原发性干燥综合征患者唇腺组织的破坏有关,二者参与了PSS的发病过程.%Objective To investigate the expression of matrix metalloproteinase - 9( MMP - 9 ) and B cell activating factor of the tumor necrosis factor family ( BAFF ) in the labial gland of patients with Primary Sjogren' s Syndrome ( PSS ) and to analyse their roles in the pathogenesis of PSS. Methods The expression of MMP -9and BAFF were detected by the Immunohistochemical method. The labial gland were obtained from 50 patients with PSS and 30 healthy controls. Results The MMP - 9 protein and BAFF protein were both over -expressed in the labial gland of patients with PSS. The mean over - expression level( 14382. 38 ± 657. 39 ) μm2, integrated optical density ( 2705. 46 ± 868. 76 )of MMP - 9 and the mean over - expression level ( 13586. 72 ± 1569.45) μm2 , integrated optical density( 2073. 57 ± 850. 73 )of BAFF in PPS patients'tissues were all significantly higher than those in normal

  5. 急性肺血栓栓塞大鼠血浆MMP-2和MMP-9的活性变化及意义%Change and significance of plasma MMP-2 and MMP-9 activity in acute pulmonary thromboembolism rat

    Institute of Scientific and Technical Information of China (English)

    靳建军; 郭军; 王晓芳; 施举红; 王静; 陆慰萱

    2012-01-01

    Objective To explore the change and significance of plasma MMP-2 and MMP-9 activity in acute pulmonary thromboembolism (PTE).Methods 72 male Sprague-Dawley rats were randomly divided into three groups:Sham group,PTE group and Statins group.Right ventricular systolic pressure and mean pulmonary arterial pressure were measured by right heart catheter at different time points following the induction of PTE.The enzymic activity of MMP-2 and MMP-9 in plasma were detected through gelatin zymography.Results Compared with Sham Group,the plasma MMP-9 activity at every time point in PTE Group increased significantly ( P < 0.05).Compared with PTE Group,the plasma MMP-9 activity at every time point in Statins Group decreased significantly ( P <0.05),but was still higher than that of Sham Group ( P <0.05).No significant difference in MMP-2 activity at every time point was observed among three groups ( P >0.05).Conclusions The plasma MMP-9 activity was increased in the PTE rats,pretreatment with simavastatin attenuated acute PTE-induced pulmonary.hypertension through attenuationing of MMP-9 activity.%目的 探讨基质金属蛋白酶2(MMP-2)和MMP-9在急性肺血栓栓塞(PTE)中的变化及意义.方法 将72只Sprague-Dawley大鼠随机分为假手术组(Sham组),肺血栓栓塞模型组(PTE组)和辛伐他汀干预组(Statins组),每组24只.在造模后2h、6h、24 h分别测定各组大鼠的右心室收缩压和肺动脉平均压.应用明胶酶谱法测定各组大鼠血浆MMP-2和MMP-9的活性.结果 PTE组大鼠各时间点的血浆MMP-9活性明显升高,与Sham组大鼠比较差异有统计学意义(P<0.05); Statins组大鼠各时间点的血浆MMP-9活性与PTE组大鼠比较明显降低,差异有统计学意义(P<0.05),但仍高于Sham组大鼠,差异有统计学意义(P<0.05).PTE组大鼠各时间点的血浆MMP-2活性有升高的趋势,但与Sham组大鼠和Statins组大鼠比较,差异无统计学意义.结论 急性PTE可引起血浆MMP-9

  6. Changes of Plasma MMP-9,NT-proBNP Levels in Children with Kawasaki Disease and Its Clinic Significance%川崎病患儿血浆MMP-9、NT-proBNP水平变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    吴镇宇; 姚丽萍

    2016-01-01

    Objective:To explore the changes and clinic significance of plasma matrix metalloproteinase-9(MMP-9) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in children with Kawasaki disease(KD).Method:Forty two children with KD in our hospital from January 2015 to January 2016 were collected and divided into two groups according to the results of echocardiography,the coronary artery lesion(CAL) group(n=18) and the non-coronary artery lesion(NCAL) group (n=24).Thirty febrile children with respiratory tract infection and twenty healthy children in the same period were chosen as the control group.The plasma MMP-9 and NT-proBNP protein levels were measured respectively.Result:The plasma MMP-9 and NT-proBNP levels in the acute phase of KD patients were all higher than those in the two control group(P<0.01),and which were significantly higher in the CAL group than in the NCAL group,the differences were statistically significant(P<0.05 ).The plasma MMP-9 and NT-proBNP levels in remission stages were siginificantly lower after treatment,and the protein level of NT-proBNP in the CAL group was still higher than that of the NCAL group,the differences were statistically significant(P<0.05).There was a positive correlation between plasma MMP-9 and NT-proBNP levels in the acute phase of KD(r=0.57,P<0.05).Conclusion:The plasma MMP-9 and NT-proBNP levels are closely related to KD cardiovascular damage,combined detection of them may have critical value for the early diagnosis of KD and the prediction of CAL.%目的:探讨基质金属蛋白酶-9(MMP-9)与N末端脑利钠肽(NT-proBNP)在川崎病(KD)患儿血浆中的变化及其意义。方法:选取2015年1月-2016年1月本院明确诊断的KD患儿42例为研究对象,根据心脏彩超分为冠状动脉损伤(CAL)组18例、无冠状动脉损伤(NCAL)组24例,另选取同期伴有发热的呼吸道感染患儿30例和门诊健康体检儿童20例作为对照组,分别测定各组MMP-9、NT-proBNP蛋白水平

  7. EFFECTS OF WATER SOLUBLE TOTAL SAPONINS OF DIOSCOREA NIPPONICA ON RSC-364 CELLS SECRETING MMP-2 AND MMP-9%穿山龙水溶性总皂苷对RSC-364细胞分泌MMP-2和MMP-9的影响

    Institute of Scientific and Technical Information of China (English)

    段一娜; 杨佳琪; 王晶; 高亚贤

    2014-01-01

    目的:观察穿山龙水溶性总皂苷对大鼠滑膜成纤维细胞系RSC-364细胞分泌基质金属蛋白酶-2(MMP-2)和MMP-9的影响。方法:应用肿瘤坏死因子-α(TNF-α)和白介素17(IL-17)刺激RSC-364细胞建立类风湿性关节炎细胞模型,并以不同剂量穿山龙水溶性总皂苷进行干预,ELISA法检测细胞培养液上清MMP-2和MMP-9的水平。结果:穿山龙水溶性总皂苷各剂量组(10、20、30mg/L)在不同时间点(24、48、72h)均可明显降低TNF-α和IL-17刺激的RSC-364细胞分泌MMP-2、MMP-9水平的升高,并呈剂量依赖性(P<0.05)。结论:穿山龙水溶性总皂苷可能通过抑制RSC-364细胞分泌MMP-2和MMP-9发挥抗类风湿性关节炎的作用。%Objective: To observe the inlfuence of water soluble total saponins of Dioscorea nipponica on rat synovial ifbroblast cell line RSC-364 cells secreting matrix metalloproteinases-2 (MMP-2) and MMP-9.Methods: Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were used to stimulate RSC-364 for establishing rheumatoid arthritis (RA) cell model, then the cell model was intervened by water soluble total saponins of Dioscorea nipponica in different dosage. ELISA was used to detect the MMP-2 and MMP-9 level in cultural supernatants of RSC-364 cells.Results:Water soluble total saponins of Dioscorea nipponica in different dosage at different time point could obviously reduce the level of RSC-364 cells secreting MMP-2 and MMP-9 stimulated by IL-17+ TNF-α, and showed dosage-dependent (P<0.05).Conclusions:Water soluble total saponins of Dioscorea nipponica may play a role in anti-RA by inhibiting RSC-364 cell secreting MMP-2 and MMP-9.

  8. 结直肠癌患者血清中MMP-2、MMP-9和MMP-14检测的临床意义%The clinical significance of MMP-2,MMP-9 and MMP-14 in patients with colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    万彦彬

    2010-01-01

    目的 探讨MMP-2、MMP-9及MMP-14在结直肠癌患者血清中的表达水平,并分析其与结直肠癌分化程度、Dukes分期及淋巴结转移等病理参数的关系,以更好的指导临床工作.方法 应用ELISA(酶联免疫吸附实验)分别检测200例结直肠癌患者(观察组)、60例健康成人(对照组)血清中MMP-2、MMP-9和MMP-14的含量.结果 观察组血清中MMP-2、MMP-9及MMP-14表达量显著高于对照组(P<0.01),观察组中不同临床特征患者血清MMP-2、MMP-9和MMP-14的表达与肿瘤分化程度、Dukes分期以及淋巴结转移有关(P<0.01),经相关性分析,MMP-2和MMP-9MMP-9和MMP-14的表达呈正相关(P均<0.05).结论 MMP-2、MMP-9和MMP-14在结直肠癌患者血清中高表达,三者可能在结直肠癌发生发展中起重要作用;早期联合检测MMP-2、MMP-9和MMP-14可能对判断患者的预后及指导临床治疗有重要价值.

  9. MMP-2、MMP-9在乳腺癌中的表达及其意义%The expression of MMP-2 and MMP-9 in breast cancer and their significance and long-term follow-up results

    Institute of Scientific and Technical Information of China (English)

    冯悦年

    2008-01-01

    目的 检测基质金属蛋白酶(MMP-2和MMP-9)与乳腺癌的淋巴结转移、病理分级、患者年龄及肿瘤大小之间的可能关系,及对术后的影响.方法 65例乳腺癌蜡块,采用免疫组化S-P法染色,以细胞浆中有棕色颗粒计数分为:阴性;弱阳性;中度阳性及强阳性.结合随访材料进行统计分析.结果 MMP-2和 MMP-9的表达与乳腺癌患者的年龄及肿瘤大小无关;MMP-2与淋巴结转移有关,无淋巴结转移者,MMP-2表达较低;有淋巴结转移者,MMP-2表达较高.MMP-9的表达与淋巴结转移情况则无关.MMP-2和MMP-9的表达与病理分级相关.二者均影响预后,MMP-2低表达组术后10年生存率为100%,MMP-2高表达组术后1、3、5及10年生存率分别为100%、86.11%、75.0%、66.67%,两组间有显著性差异(P《0.01);MMP-9低表达组术后10年生存率为100%,MMP-9高表达组术后1、3、5及10年生存率分别为100%、86.49%、72.97%、64.86%,两组间有显著性差异(P《0.01).结论 MMP-2和MMP-9的表达与乳腺癌病理学分级有关;MMP-2与淋巴结转移有关,而MMP-9与淋巴结转移无关.二者高表达生存率均降低,影响预后.

  10. Influence of Curcumin on Matrix Metalloproteinase(MMP)-2 and MMP-9 Expressions in Spinal Cord of Experimental Allergic Encephalomyelitis%姜黄素对EAE大鼠脊髓中MMP-2、MMP-9表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨学志; 王赵伟; 李剑敏; 王贤亲; 张正学; 朱洁瑾

    2013-01-01

    Objective: To investigate the influence of curcumin on matrix metalloproteinase ( MMP ) -2 and MMP -9 expressions in spinal cord of experimental allergic encephalomyelitis (EAE) . Methods: The animal model was established in SD rats by injecting guinea pig spinal cord homogenate in complete Freund's adjuvant (CFA)and bordetella pertussis vaccine. Experimental group was given curcumin, and the changes of clinical symptoms were observed every day. Pathological changes of brain were observed by Hematoxylin and Eosin ( HE) staining. Real - time PCR was performed to test the transcriptional levels of MMP - 2 and MMP - 9 in cervical cord. Result: Compared with EAE group, the clinical scores and disease course were obviously reduced in curcumin group, furthermore the rats were recuperated quickly. The infiltration of inflammatory cells in central nerval system were obviously lessened. The transcriptional level of MMP - 9 was descend, the discrepancy of EAE and curcumins groups was significant, but the transcriptional level of MMP -2 in the two groups had no difference. Conclusion: Curcumin has therapeutic action on EAE, concerned with the inhibition of inflammatory cell infiltration and reducing the transcriptional level of MMP -9.%目的:探讨姜黄素对EAE大鼠脊髓中MMP-2、MMP-9活性的影响.方法:采用豚鼠脊髓匀浆诱导EAE模型,治疗组给予姜黄素进行干预,观察行为学变化,HE染色观察脑组织病理改变,real-time PCR检测颈髓组织MMP-2、MMP-9mRNA表达.结果:与EAE组相比,姜黄素治疗组临床评分明显下降,病程缩短,而且恢复较快;中枢炎性细胞浸润明显减少;MMP-9的转录水平明显下降,两组之间差异具有显著性,而MMP-2的水平两者无明显差异.结论:姜黄素对EAE具有一定的治疗作用,可能与抑制炎症细胞浸润及降低MMP-9的水平有关.

  11. CD147/MMP-9通路上调改善自发性高血压大鼠早期心室重构%Upregulation of CD147/MMP-9 pathway attenuates early left ventricular remodeling in rats with spontaneous hypertension

    Institute of Scientific and Technical Information of China (English)

    周万兴; 李博维; 杨小蓉; 周玉良; 谭永锦; 袁丛聪; 宋玉兰; 陈骁; 张卫

    2015-01-01

    目的:探讨CD147/MMP-9通路对自发性高血压大鼠(SHR)早期心室重构的影响。方法:8周龄雄性 SHR 随机分成 SHR、CD147和 CD147+ DOX 组(n =10/组),8周龄雄性 WKY 大鼠为对照组(WKY组,n =10)。 CD147及CD147+ DOX 组予人重组CD147(600 ng/kg 1.5 mL)、SHR 及WKY 组予等量生理盐水,静注,每周1次。 CD147+ DOX组加多西环素(DOX,30 mg/kg,1.5 mL),其他组加生理盐水灌胃每天1次。第56天超声心动图检查、测左心室重量指数(LVWI)、切片(HE、VG染色)观察心肌细胞和胶原增殖、western blot 测心肌 MMP-9、TIMP-1、CD147、Ⅰ和Ⅲ型胶原水平。结果:与 WKY 组比,SHR 组心肌 CD147、MMP-9MMP-9/TIMP-1明显低(P <0.05);心肌细胞肥大、部分纤维断裂、胞浆溶解坏死,胶原容积分数(CVF)Ⅰ、Ⅲ型胶原显著增高(P <0.05)。而与SHR 组比,CD147组CD147、MMP-9MMP-9/TIMP-1明显增高,心肌细胞形态和排列改善,LVWI、CVF、Ⅰ、Ⅲ型胶原明显降低。但CD147+DOX 组尽管CD147、MMP-9MMP-9/TIMP-1比CD147组无明显降低,CVF与Ⅰ、Ⅲ型胶原却明显增高,心肌细胞肥大及纤维断裂现象再次出现。结论:SHR早期心室重构可能与CD147/MMP-9通路受抑制有关,输入CD147上调该通路可以改善该心室重构。%Objective To investigate the effects of CD147/MMP-9 pathway on early left ventricular remodeling Methods 30 healthy eight-week male SHR were divided into 3 groups (n = 10 for each group). SHR group received tail vein injections of normal saline weekly; CD147 group received CD147 of 600 ng·kg-1 weekly; and CD147+DOX group received CD147 of 600 ng/kg weekly and intragastric administration of DOX ( doxycycline ) of 30 mg/kg daily . 10 healthy eight-week male Wistar-Kyoto rats (WKY group) were treated as SHR group. Echocardiography, myocardial sections microscopy examination (HE and VG

  12. Plasma LP-PLA2 and MMP-9 in patients with acute coronary syndrome and its clinical significance%急性冠脉综合征患者LP-PLA2与MMP-9血浆水平及临床意义

    Institute of Scientific and Technical Information of China (English)

    陈锦峰; 徐新; 马绍椿; 唐良秋; 张社兵; 江志平; 范文茂; 尹建国

    2011-01-01

    Objective To investigate diagnostic value of plasma lipoprotein - associated phospholipase A2 ( LP -PLA2 ) and matrix metalloproteinases - 9 ( MMP - 9 ) for acute coronary syndrome, as well as effects of the percutaneous transluminal coronary intervention ( PCI ) on them. Methods Proved with coronal artery angiography , 28 controls without coronary artery stenosis, 27 patients with acute cornary syndrome. ( ACS ) and 28 patients with stable angina pectoris ( SAP ) were enrolled in for comparison. Blood samples were collected for assessment of plasma LP - PLA2 and MMP - 9 expression with ELISA at hospitalization form all subjects and 1 month after PCI from patients with ACS. Results Significantly higher plasma expression levels of LP - PLA2 and MMP - 9 ( 706. 00 ± 149. 91 ng/mL and 7. 06 ± 6. 22 ng/mL )were observed in ACS group than those in SAP group ( 427. 75 ±44. 58 ng/mL vs 2. 45 ± 1. 23 ng/mL, P < 0. 001 ) and health controls ( 267. 69 ±92. 67 ng/mL vs 1. 84 ±0. 46 ng/mL, P <0. 001 ). Furthermore, comparing with baseline levels, significant reduction of plasma LP - PLA2 and MMP -9 was observed 1 month after PCI in ACS group ( 520. 00 ±30.36 ng/ml vs 706. 00 ± 149. 91 ng/mL, 2. 52 ± 1. 54 ng/mL vs 7. 06 ±6. 22 ng/mL, P < 0. 001 ). Meanwhile , significant positive correlation was revealed between the plasma LP - PLA2 and MMP -9 in ACS group ( r = 0. 018, F = 6. 032, P <0. 05 ). Conclusion Up - regulation of LP - PLA2 and MMP - 9 in ACS patients suggests their participating in pathogenesis in ACS as inflammatory factors. Combined diagnosis using LP - PLA2 and MMP - 9 is available due to their positive correlation in ACS group. PCI lower the plasma level of LP - PLA2 and MMP - 9 in ACS patients, cueing that PCI stahilizes coronary atherosclerosis lesion.%目的 探索脂蛋白相关磷脂酶A2(LP-PLA2)与基质金属蛋白酶-9(MMP-9)的血浆水平在预测急性冠脉综合征(acute coronary syndrome,ACS)高危人群的临床价值,以及冠

  13. 消癌平注射液下调MMP-9基因表达抑制卵巢癌细胞Caov-3迁移机制的研究%Xiaoaiping Injection Inhibits Cell Migration by Reducing MMP-9 Gene Expression in Human Ovarian Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    王淳; 董秀; 王梅; 王晓波

    2012-01-01

    目的:研究中药消癌平注射液下调MMP-9基因表达,抑制卵巢癌细胞Caov-3迁移的机制.方法:利用消癌平注射液干预体外培养的卵巢癌Caov-3细胞,分别应用:细胞划痕实验观察细胞的迁移水平;肿瘤细胞侵袭实验(Transwell小室法)观察细胞侵袭能力;RT-PCR实验检测卵巢癌细胞中金属蛋白酶MMP-9基因表达水平.以金属蛋白酶MMPs特异性抑制剂-Doxycyclin作为阳性对照,同时应用PBS作空白对照.结果:消癌平可有效抑制Caov-3细胞迁移,与空白对照组相比差异有统计学意义(P0.05);消癌平还可部分抑制血清诱导的Caov-3细胞穿过Transwell小室,其抑制效果与Doxycyclin相似;此外,消癌平还能够下调MMP-9基因表达水平.结论:消癌平下调MMP-9基因表达,抑制卵巢癌Caov-3细胞迁移.%Objective: To study the inhibitory mechanism of an injection of the Chinese medicine Xiaoaiping ( XAP ) on the migration of human ovarian cancer Caov-3 cells via reduced matrix metalloproteinase-9 ( MMP-9 ) gene expression Methods: The ovarian cancer Caov-3 cells were treated with XAP in vitro. The inhibitor doxycyclin was also applied to the MMPs as the positive control, whereas phosphate-buffered saline served as the blank control. Wound healing and cell invasion assays using Transwell chambers were used to investigate the antimetastatic activities of XAP. The MMP-9 expression was detected via real-time polymerase chain reaction and Western blot analysis. Results: XAP effectively inhibited Caov-3 cell migration and invasion and decreased the MMP-9 gene and protein expression levels (P 0.05 ). Conclusion: XAP inhibits Caov-3 cell migration by decreasing the MMP-9 expression.

  14. Changes of MMP-9 and IL-1β in serum and cerebrospinal-fluid in children with central nervous system infection

    Institute of Scientific and Technical Information of China (English)

    Shu-Qin Jiao

    2016-01-01

    Objective:To provide a new basis for the detection of the central nervous system infection cases, we explored and compared the role of cerebrospinal-fluid (CSF), matrix metalloproteinases 9 (MMP-9) and interleukin 1 (the level of IL -1β) in the central nervous system (CNS).Methods:Sixty cases of children acute central nervous system infection were selected, including 30 cases of viral encephalitis children (VE) and 30 cases of purulent meningitis children (PM). Forty cases of non-central nervous system infection children were control group. The serum albumin (SA1b) of each group was detected by full-automatic analysis instrument, and the CSF albumin (CA1b) was detected by immunoephelometry and the albumin index (AQ) was accounted. ELISE was used to detect the levels of MMP-9 and IL-1β in serum and cerebrospinal-fluid.Results:The level of MMP-9 in the serum of groups of VE, PM and control were (267.84 ± 91.88) μg/L, (488.98 ± 159.07) μg/L and (133.04 ± 31.68) μg/L, while in the CSF were (37.18 ± 17.78) μg/L, (117.9 ± 42.87) μg/L and (10.36 ± 5.43) μg/L; The level of IL-1β in serum of groups of PM, VE and control were (19.69 ± 11.12) ng/L, (24.37 ± 4.13) ng/L and (15.01 ± 3.89) ng/L, while in the CSF were (66.94 ± 10.65) ng/L, (106.27 ± 12.79) ng/L and (49.98 ± 12.59) ng/L; The level of CAlb were (0.53 ± 0.15) g/L, (1.05 ± 0.27) g/L and (0.17 ± 0.07) g/L and AQ were (13.75 ± 3.44), (26.99 ± 7.28) and (4.63 ± 2.04). The PM, VE were respectively compared with the control, the levels of IL-1β and MMP-9 in serum and CSF all increased, with statistically significant difference.The VE, compared to the PM, the level of IL-1β in serum and CSF all decreased, with statistically significant difference; The level of MMP-9 in serum and CSF all decreased, with statistically significant difference. The level of CA1b and AQ in the VE and PM all increased, with a statistically significant difference. The level of MMP-9 and IL-1β in serum and CSF of the

  15. Detection of the matrix metalloproteinases MMP-2 and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 in llama (Lama glama) oviduct.

    Science.gov (United States)

    Zampini, R; Argañaraz, M E; Miceli, D C; Apichela, S A

    2014-06-01

    Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are involved in several reproductive events like oocyte-spermatozoa interaction and semen liquefaction. In order to study their role in the llama oviductal reproductive process, MMP activity in oviductal fluid (OF) was assayed. Considering that llama genome sequences are partially known, a strategy to procure cDNA sequences of MMP-2, MMP-9, TIMP-1 and TIMP-2 was designed. Afterwards, their expression patterns in the different llama oviductal segments were assayed. Gelatine zymograms detected 62 and 94 kDa protease activities that matched MMP-2 and pro-MMP-9, respectively. Expression pattern analysis showed that MMP and TIMP mRNAs were present in ampulla, isthmus, utero-tubal junction (UTJ) and papilla. Altogether, these findings support the argument that MMPs/TIMPs are produced in the oviduct and secreted into the oviductal lumen. Our results encourage further studies to elucidate the role of these proteins in reproductive oviductal events.

  16. THE ASSOCIATION BETWEEN MATRIX METALLOPROTEINASE-9 (MMP-9 WITH HIGH SENSITIVE TROPONIN T (hs-TnT IN PATIENT WITH ACUTE MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    I Putu Gede Eka Ariawan Suyasa

    2015-10-01

    Full Text Available Mechanism of acute myocardial infarction (AMI is previously due to atherosclerotic plaque rupturewith occurs because extra-cellular matrix of plaque fibrous cap destruction or degradation by proteaseenzyme matrix metalloproteinase-9  (MMP-9, which released by macrophage cell.Increased plasmaMMP-9  is  predisposition  factor  of  atherosclerotic  plaque  rupture  in AMI  and  followed  by  acutethrombosis inside coronary artery lumen which caused myocardial ischemic and clinical sign of AMI. Ifthe ischemic process continuous and ongoing that can caused myocardial necrosis which can increasedplasma troponin. High sensitive troponin T (hs-TnT newly and more sensitive detection of plasmacTn-T  than conventional.The aim of  this study was  to determined  the association between plasmaMMP-9 with hs-TnT in AMI patients.This study was a cross-sectional observational which performedin 62 patients with AMI which enrolled by consecutive sampling at Sanglah Hospital Denpasar fromDecember 2011 until December 2012. MMP-9 and hs-TnT plasma level were measured 48 hours afteronset IMA. Sixty two patients AMI were involved in this study consist of 35 STEMI patients (56.5%and 27 NSTEMI patients (43.5%, the mean plasma MMP-9 was 23.9 (SD 0.42 ng/mL and hs-TnT was464.7 (SD 39.3 ng/mL.The results of this study were positive correlation between MMP-9 and hs-TnTAMI  patients  (r=  0.507; Y=  -  650.6 +  46.7(X1; P<0.0001;  plasma MMP-9  and  onset  of AMI wereinfluenced to plasma hs-TnT with formulationY = - 815.0 + 46.5(X1+ 20.7(X2; (â MMP-9=46.5(95%CI: 24.7 to 68.4; P<0.0001; â onset AMI=20.7(95%CI : 2.1 to 39.4; P=0.030 and there was more strongercorrelation betweenMMP-9 and hs-TnT in STEMI group than NSTEMI. [MEDICINA 2015;46:22-27].Mekanisme terjadinya infark miokard akut (IMA didahului oleh proses ruptur plak aterosklerosisdan diawali dengan destruksi atau degradasi matriks ekstraseluler fibrus cap plak oleh enzim proteaseyang

  17. Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-kB/MMP-9 Pathway

    Directory of Open Access Journals (Sweden)

    Chun-Tang Chiu

    2015-06-01

    Full Text Available Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9. The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt/NF-kB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-kB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.

  18. Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice.

    Science.gov (United States)

    Wu, Bin-Nan; Kuo, Kung-Kai; Chen, Yu-Hsun; Chang, Chain-Ting; Huang, Hung-Tu; Chai, Chee-Yin; Dai, Zen-Kong; Chen, Ing-Jun

    2016-08-17

    KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) has been reported to cause hepatic fat loss. However, the action mechanisms of KMUP-1 in obesity-induced steatohepatitis remains unclear. This study elucidated the steatohepatitis via matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor α (TNFα), and related lipolysis via hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) by KMUP-1. KMUP-1 on steatohepatitis-associated HSL/p-HSL/ATGL/MMP-9/TNFα/interleukin-10 (IL-10) and infiltration of M1/M2 macrophages in obese mice were examined. KMUP-1 was administered by oral gavage from weeks 1-14 in high-fat diet (HFD)-supplemented C57BL/6J male mice (protection group) and from weeks 8-14, for 6 weeks, in HFD-induced obese mice (treatment group). Immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining of tissues, oil globules number and size, infiltration and switching of M1/M2 macrophages were measured to determine the effects on livers. IL-10 and MMP-9 proteins were explored to determine the effects of KMUP-1 on M1/M2 macrophage polarization in HFD-induced steatohepatitis. Long-term administration of KMUP-1 reversed HFD-fed mice increased in body weight, sGOT/sGPT, triglyceride (TG) and glucose. Additionally, KMUP-1 decreased MMP-9 and reactive oxygen species (ROS), and increased HSL/p-HSL and IL-10 in HFD mice livers. In conclusion, KMUP-1, a phosphodiesterase inhibitor (PDEI), was shown to reduce lipid accumulation in liver tissues, suggesting that it could be able to prevent or treat steatohepatitis induced by HFD.

  19. Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice

    Directory of Open Access Journals (Sweden)

    Bin-Nan Wu

    2016-08-01

    Full Text Available KMUP-1 (7-[2-[4-(2-chlorobenzenepiperazinyl]ethyl]-1,3-dimethylxanthine has been reported to cause hepatic fat loss. However, the action mechanisms of KMUP-1 in obesity-induced steatohepatitis remains unclear. This study elucidated the steatohepatitis via matrix metallopeptidase 9 (MMP-9 and tumor necrosis factor α (TNFα, and related lipolysis via hormone sensitive lipase (HSL and adipose triglyceride lipase (ATGL by KMUP-1. KMUP-1 on steatohepatitis-associated HSL/p-HSL/ATGL/MMP-9/TNFα/interleukin-10 (IL-10 and infiltration of M1/M2 macrophages in obese mice were examined. KMUP-1 was administered by oral gavage from weeks 1–14 in high-fat diet (HFD-supplemented C57BL/6J male mice (protection group and from weeks 8–14, for 6 weeks, in HFD-induced obese mice (treatment group. Immunohistochemistry (IHC and hematoxylin and eosin (H&E staining of tissues, oil globules number and size, infiltration and switching of M1/M2 macrophages were measured to determine the effects on livers. IL-10 and MMP-9 proteins were explored to determine the effects of KMUP-1 on M1/M2 macrophage polarization in HFD-induced steatohepatitis. Long-term administration of KMUP-1 reversed HFD-fed mice increased in body weight, sGOT/sGPT, triglyceride (TG and glucose. Additionally, KMUP-1 decreased MMP-9 and reactive oxygen species (ROS, and increased HSL/p-HSL and IL-10 in HFD mice livers. In conclusion, KMUP-1, a phosphodiesterase inhibitor (PDEI, was shown to reduce lipid accumulation in liver tissues, suggesting that it could be able to prevent or treat steatohepatitis induced by HFD.

  20. Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice

    Science.gov (United States)

    Wu, Bin-Nan; Kuo, Kung-Kai; Chen, Yu-Hsun; Chang, Chain-Ting; Huang, Hung-Tu; Chai, Chee-Yin; Dai, Zen-Kong; Chen, Ing-Jun

    2016-01-01

    KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) has been reported to cause hepatic fat loss. However, the action mechanisms of KMUP-1 in obesity-induced steatohepatitis remains unclear. This study elucidated the steatohepatitis via matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor α (TNFα), and related lipolysis via hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) by KMUP-1. KMUP-1 on steatohepatitis-associated HSL/p-HSL/ATGL/MMP-9/TNFα/interleukin-10 (IL-10) and infiltration of M1/M2 macrophages in obese mice were examined. KMUP-1 was administered by oral gavage from weeks 1–14 in high-fat diet (HFD)-supplemented C57BL/6J male mice (protection group) and from weeks 8–14, for 6 weeks, in HFD-induced obese mice (treatment group). Immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining of tissues, oil globules number and size, infiltration and switching of M1/M2 macrophages were measured to determine the effects on livers. IL-10 and MMP-9 proteins were explored to determine the effects of KMUP-1 on M1/M2 macrophage polarization in HFD-induced steatohepatitis. Long-term administration of KMUP-1 reversed HFD-fed mice increased in body weight, sGOT/sGPT, triglyceride (TG) and glucose. Additionally, KMUP-1 decreased MMP-9 and reactive oxygen species (ROS), and increased HSL/p-HSL and IL-10 in HFD mice livers. In conclusion, KMUP-1, a phosphodiesterase inhibitor (PDEI), was shown to reduce lipid accumulation in liver tissues, suggesting that it could be able to prevent or treat steatohepatitis induced by HFD. PMID:27548140

  1. Differential expression of MMP-2, MMP-9 and TIMP proteins in thoracic aortic aneurysm - comparison with and without bicuspid aortic valve: a meta-analysis.

    Science.gov (United States)

    Rabkin, Simon W

    2014-11-01

    Hintergrund: Es wird angenommen, dass das Gleichgewicht der Matrix- Metalloproteasen (MMPs) und der Gewebeinhibitoren von Metalloproteinasen (TIMPs ) in der Aorta eine entscheidende Rolle bei der Ausbildung von Aneurysmen spielt. Das Ziel dieser Studie war es, eine Meta-Analyse von Studien durchzuführen, die die Protein-Expression von MMPs und TIMPs bei Aneurysmen der Aorta ascendens (TAA) untersuchten. Dabei sollte zwischen trikuspiden (TAV) und bikuspiden Aortenklappen (BAV) unterschieden werden. Methoden: Medline und Embase OvidSP wurden systematisch nach Studien abgefragt, die MMPs oder TIMPs aus TAAs und Kontrollen untersuchten. Eine entsprechende Suche erfolgte zum Vergleich zwischen BAV und TAV. Ergebnisse: Acht Studien erfüllten die Einschlusskriterien. Es gab einen signifikanten Anstieg der MMP-9 und keine Veränderung in MMP-2 in der Aorta von Personen mit TAA (N = 106 ) im Vergleich zur Kontrolle (n = 30). Zudem gab es eine hochsignifikante Verringerung der TIMP-1 und TIMP-2 in TAA (N = 93) im Vergleich zur Kontrolle (n = 24 ), was zu einem MMP-9 zu TIMP-1 oder TIMP-2-Verhältnis von mehr als 3,5 im Vergleich zu Kontrollen führte. Es fand sich eine hochsignifikante Erhöhung der MMP-2, aber nicht der MMP-9 in TAAs mit BAV (N = 112 ) im Vergleich zu TAV (N = 53). Es gab eine signifikante Reduktion von TIMP-1 bei BAV im Vergleich zu TAV, aber keine Änderung von TIMP-2, TIMP-3 oder TIMP-4 . Schlussfolgerungen: Diese Daten deuten darauf hin, dass MMP eine Rolle in der Pathogenese von TAA spielt. Es gibt eine unterschiedliche Expression mit erhöhtem MMP-9 und verminderten TIMP-1 und -2 bei den häufigsten Formen des TAA. MMP-2 ist erhöht und nur TIMP-1 vermindert bei TAA mit BAV im Vergleich zu TAV.

  2. Levels of plasma RANTES and MMP-9 and their correlation to coronary artery stenosis in patients with coronary heart disease%冠心病患者血浆RANTES及MMP-9水平及与冠状动脉狭窄的相关性研究

    Institute of Scientific and Technical Information of China (English)

    徐娅楠; 赵亚珍; 浦奎

    2011-01-01

    Objective To investigate the levels of plasma regulated on activation normal T cell expressed and secreted ( RANTES ) and matrix metalloproteinase-9 ( MMP-9 ) and their correlation to coronary artery stenosis in patients with coronary heart disease ( CHD ). Methods The hospitalized patients with CHD ( n =64) were chosen, a-mong them 26 with unstable angina ( UA group ),16 with acute myocardial infarction ( AMI group ),and 22 with stable angina ( SA group ). At the same time 20 cases with normal coronary angiography ( CAG ) were chosen as the control group. The levels of plasma MMP-9 and RANTES were detected, compared and analyzed by using enzyme-linked immu-nosorbent assay ( ELISA ). Results The levels of plasma MMP-9 and RANTES were significantly higher in UA group and AMI group than those in SA group and control group ( P <0. 01 ),higher in AMI group than those in UA group ( P <0. 05 ) ,and higher in SA group than those in control group without statistical significance ( P >0. 05 ). The concentration of plasma RANTES was greatly correlated to MMP-9 among UA group, AMI group and SA group ( r =0.794,P < 0.01 ),plasma RANTES concentration was greatly correlated to Gensini score ( r =0. 874,P <0.01 ),and Gensini score was greatly correlated to plasma MMP-9 concentration ( r =0.716,P <0. 01 ). Conclusion The expressions of RANTES and MMP-9 increase in the plasma of patients with acute coronary syndrome and are correlated to the degree of coronary artery stenosis.%目的 探讨冠心病患者血浆调节正常T细胞表达和分泌的细胞因子(RANTES)及基质金属蛋白酶-9(MMP-9)的水平及与冠状动脉狭窄的相关性.方法 选取住院的冠心病患者64例,其中不稳定性心绞痛患者26例(UA组)及急性心肌梗死患者16例(AMI组),稳定性心绞痛患者22例(SA组),同期冠状动脉造影正常的20例患者作为对照组.采用酶联免疫吸附法测定各组血浆MMP-9及RANTES含量,并进行对比分析.结果 血浆MMP-9

  3. Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP-9.

    Science.gov (United States)

    Yan, Shuangquan; Wang, Yiran; Liu, Panpan; Chen, Ali; Chen, Mayun; Yao, Dan; Xu, Xiaomei; Wang, Liangxing; Huang, Xiaoying

    2016-01-01

    Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.

  4. Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP-9

    Directory of Open Access Journals (Sweden)

    Shuangquan Yan

    2016-01-01

    Full Text Available Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP- 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.

  5. Sinomenine influences capacity for invasion and migration in activated human monocytic THP-1 cells by inhibiting the expression of MMP-2, MMP-9, and CD147

    Institute of Scientific and Technical Information of China (English)

    Yang-qiong OU; Li-hua CHEN; Xue-jun LI; Zhi-bin LIN; Wei-dong LI

    2009-01-01

    Aim: The aim of this study was to investigate the mechanism of the effects of Sinomenine (SIN) on the invasion and migration ability of activated human monocytic THP-1 cells (A-THP-1). Sinomenine is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum.Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-ac-etate (PMA). Cells were treated with different concentrations of SIN. The invasion and migration ability of cells was tested by in vitro transwell assays. The levels of CD147 and MMPs were evaluated by flow cytometric analysis and zymographic analysis, respectively. The mRNA expression of CD147, MMP-2, and MMP-9 was measured by RT-PCR. Results: The invasion and migration ability of A-THP-1 cells was significantly inhibited by SIN in a concentration-depen-dent fashion; at the same time, the levels of CD147, MMP-2, and MMP-9 were markedly down-regulated. This inhibitory effect was most notable at concentrations of 0.25 mmol/L and 1.00 mmol/L (P<0.01). Conclusion: A possible mechanism of the inhibitory effect of SIN on cell invasion and migration ability is repression of the expression of MMP-2 and MMP-9, which strongly correlates with the inhibition of CD147 activity.

  6. High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression.

    Science.gov (United States)

    Sun, Xian-Fu; Shao, Ying-Bo; Liu, Ming-Ge; Chen, Qi; Liu, Zhao-Jun; Xu, Bin; Luo, Su-Xia; Liu, Hui

    2017-05-01

    Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.

  7. High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China

    Directory of Open Access Journals (Sweden)

    Han Ju

    2012-02-01

    Full Text Available Abstract Background Osteosarcoma is a malignant tumor with high ability to form invasion and metastasis. Identifying prognostic factor in osteosarcoma is helpful to select those patients for more aggressive management. Our study evaluated serum alkaline phosphatase (ALP cooperating with matrix metalloproteinase-9 (MMP-9 as an important prognostic predictor for local recurrence and distant metastasis of osteosarcoma. Methods 177 cases were included from the osteosarcoma patients treated at 1st Affiliated Hospital of Sun Yat-sen University (1999-2008. Pre-chemotherapy serum ALP (pre-ALP were studied and correlated with tumor recurrence, lung metastasis and patient survival. MMP-9 protein in tumor tissues was detected by immunohistochemistry and correlated with pre-ALP level. Results Pre-ALP were partitioned into normal, high, and very high groups, in each group the incidence of metastases was 12.2%, 21.2% and 34.6%, respectively (p = 0.007. In the three groups the mean disease-free survival (DFS was 57 ± 3.15, 28 ± 3.57 and 14 ± 3.35 months, respectively (p Conclusions Pre-ALP was an independent prognostic factor for the survival of osteosarcoma patients in south China, and correlated with MMP-9 expression and lung metastasis. ALP can also serve as a prognostic marker for treatment, and merit large-scale validation studies.

  8. High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China.

    Science.gov (United States)

    Han, Ju; Yong, Bicheng; Luo, Canqiao; Tan, Pingxian; Peng, Tingsheng; Shen, Jingnan

    2012-02-15

    Osteosarcoma is a malignant tumor with high ability to form invasion and metastasis. Identifying prognostic factor in osteosarcoma is helpful to select those patients for more aggressive management. Our study evaluated serum alkaline phosphatase (ALP) cooperating with matrix metalloproteinase-9 (MMP-9) as an important prognostic predictor for local recurrence and distant metastasis of osteosarcoma. 177 cases were included from the osteosarcoma patients treated at 1st Affiliated Hospital of Sun Yat-sen University (1999-2008). Pre-chemotherapy serum ALP (pre-ALP) were studied and correlated with tumor recurrence, lung metastasis and patient survival. MMP-9 protein in tumor tissues was detected by immunohistochemistry and correlated with pre-ALP level. Pre-ALP were partitioned into normal, high, and very high groups, in each group the incidence of metastases was 12.2%, 21.2% and 34.6%, respectively (p = 0.007). In the three groups the mean disease-free survival (DFS) was 57 ± 3.15, 28 ± 3.57 and 14 ±