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Sample records for camp-induced mmp-2 expression

  1. Expressions of MMP-2-PEX and MMP-2 in invasive pituitary adenomas and its significance%MMP-2-PEX与MMP-2在侵袭性垂体腺瘤中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    屈洪涛; 杨伊林; 王穗暖; 刘运生; 王强; 董博; 毛宇敏

    2013-01-01

    Objective To investigate the expressions of matrix metalloproteinase-2 hemopexin domain (MMP-2-PEX) and matrix metalloproteinase-2 (MMP-2) in invasive pituitary adenomas and non-invasive pituitary adenomas, and to evaluate the relationship between the expressions of MMP-2-PEX and MMP-2 and the invasion of pituitary adenomas. Methods The expressions of MMP-2-PEX and MMP-2 mRNA were examined by reverse transcription-polymerse chain reaction assay. The relation between MMP-2-PEX and MMP-2, and the correlation between expression of MMP-2-PEX, MMP-2 and invasiveness of pituitary adenomas were studied. Results The expression of MMP-2-PEX mRNA in invasive pituitary adenomas was significantly lower than that of non-invasive pituitary adenomas (P < 0.01). The expression of MMP-2 mRNA in invasive pituitary adenomas was significantly higher than that of non-invasive pituitary adenomas (P<0.01). mRNA level of MMP-2-PEX was negatively related with mRNA of MMP-2 , and there was no correlation between them in non-invasive pituitary adenomas. Conclusion Low level of MMP-2-PEX is closely related with high level of MMP-2, so MMP-2-PEX and MMP-2 can be used as an important index for the evaluation of invasiveness of pituitary adenoma.%目的 研究基质金属蛋白酶-2在C端的血红素样结构域(MMP-2-PEX)和基质金属蛋白酶-2(MMP-2)在侵袭性垂体腺瘤中的表达及其意义.方法 用逆转录酶-聚合酶链反应(RT-PCR)法检测116例垂体腺瘤标本的MMP-2-PEX及MMP-2的表达,分析其与侵袭性垂体腺瘤的关系及两者之间的相关性.结果 侵袭性垂体腺瘤组MMP-2-PEX mRNA表达较非侵袭性垂体腺瘤组显著降低(P<0.01).侵袭性垂体腺瘤组的MMP-2 mRNA表达明显高于非侵袭性垂体腺瘤组(P<0.01).侵袭性垂体腺瘤组中MMP-2-PEX mRNA表达与MMP-2 mRNA表达呈负相关(r=-0.66,P<0.05),而非侵袭性腺垂体腺瘤组中无相关性(r =-0.22,P>0.05).结论 MMP-2-PEX低表达及MMP-2高表达与垂体腺瘤的侵袭性密切相关,MMP

  2. CD44 and MMP-2 expression in urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Gülgün ERDOĞAN

    2008-09-01

    Full Text Available Aim: CD44, one of the adhesion molecules, is thought to play an important role in cell-cell and cell-matrix interactions. Matrix metalloproteinases are degradative enzymes that remodel extracellular components. In this study the relation of MMP-2 and CD44 expressions with the histologic classification and the pathologic stage of urothelial carcinoma was revealed using immunohistochemistry.Material and Methods: Thirty-nine patients with urothelial carcinoma of the bladder were studied. The histological classification was performed according to WHO criteria. Patients were grouped as infiltrating urothelial carcinoma, low grade non-invasive papillary urothelial carcinoma, and high grade non-invasive papillary urothelial carcinoma. The pathological staging was done according to the TNM classification. Immunohistochemical staining using CD44 and MMP-2 antibodies was performed on tissue blocks.Results: CD44 immunoreactivity was detected in 77% (30/39 of the tumours which was significantly higher in non-invasive papillary urothelial carcinomas, low grade non-invasive papillary urothelial carcinomas, high grade infiltrating urothelial carcinomas (p≥0.05. MMP-2 expression was observed in 69% (27 of 39 of the tumours. There were no significant differences in MMP-2 expression between various histologic subtypes and noninvasive and infiltrative tumours.Conclusion: In conclusion, higher expression of CD44 is inversely correlated with infiltrative potential of urothelial carcinoma. These results should be supported by further studies.

  3. Immunohistochemical expression of MMP-14 and MMP-2, and MMP-2 activity during human ovarian follicular development

    OpenAIRE

    2014-01-01

    BACKGROUND: The aim of this study was to investigate the presence of MMP-14 and MMP-2 during human ovarian follicular development using immunohistochemistry, and the activity of MMP-2 in follicular fluid using zymography. METHODS: Ovarian tissue collected from the archives of the Department of Pathology was examined and medical records and histopathology were reviewed. Follicular fluids were collected at the IVF-department and analyzed using zymography. RESULTS: MMP-14 and MMP-2 were increasi...

  4. Immunohistochemical expression of MMP-14 and MMP-2, and MMP-2 activity during human ovarian follicular development

    NARCIS (Netherlands)

    Vos, M.C.; Wurff, A.A. van der; Last, J.T.; Boed, E.A. de; Smeenk, J.M.J.; Kuppevelt, T.H. van; Massuger, L.F.A.G.

    2014-01-01

    BACKGROUND: The aim of this study was to investigate the presence of MMP-14 and MMP-2 during human ovarian follicular development using immunohistochemistry, and the activity of MMP-2 in follicular fluid using zymography. METHODS: Ovarian tissue collected from the archives of the Department of Patho

  5. 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.

  6. Lymph node micrometastasis and its correlation with MMP-2 expression in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ze-Yu Wu; Jing-Hua Li; Wen-Hua Zhan; Yu-Long He

    2006-01-01

    AIM: To examine matrix metalloproteinase-2 (MMP-2)expression in gastric cancer tissues and to evaluate its relationship with lymph node micrometastasis.MATERIALS: The authors studied 850 lymph nodes resected from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenetomy using reverse transcription polymerase chain reaction (RT-PCR)assay in addition to H-E staining. MMP-2 expression of the tumor tissues was detected by immunohistochemical technique (EliVisionTM plus).RESULTS: MMP-2 expression was positive in 21 (70%)cases and negative in 9 (30%) cases. No significant correlations were found between MMP-2 expression and other variables such as age, gender, tumor location,tumor diameter, Lauren classification and lymphatic invasion. In contrast, MMP-2 expression correlated significantly with depth of tumor infiltration (P =0.022), lymph node metastasis (P = 0.030) and tumor differentiation (P = 0.043). Lymph node micrometastases were detected in 77 (12.5%) lymph nodes of 14 (46.7%)gastric carcinoma patients. MMP-2 expression was positive in 12 (85.7%) of the 14 patients with lymph node micrometastasis, and in 9 (56.3%) of the 16patients without lymph node micrometastasis (P = 0.118).CONCLUSIONS: Our results demonstrate that MMP-2 expression has significant correlation with tumor invasion, tumor differentiation and lymph node metastases. MMP-2 expression may be an important biological characteristics and significant prognostic parameter of gastric carcinoma. We also conclude that MMP-2 may participate in the development of lymph node micrometastasis of gastric carcinoma. Further investigations are needed to draw a conclusion.

  7. Expression of MMP-2,TIMP-2 protein and the ratio of MMP-2/TIMP-2 in gallbladder carcinoma and their significance

    Institute of Scientific and Technical Information of China (English)

    Yue-Zu Fan; Jing-Tao Zhang; Hu-Chuan Yang; Yao-Qin Yang

    2002-01-01

    AIM: To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinicalpathological parameters of patients with gallbladder carcinoma.METHODS: Carcinomas (n=45) and polypoid lesions (n=15) of the gallbladder were studied for the expression of MMP-2 and TIMP-2 protein by immunohistochemical avidin-biotin-complex method and image analysis. Clinicalpathological data of patients with gallbladder carcinoma such as histological type, grade of differentiation, level of infiltration, liver invasion and lymph node involvement, etc, were recorded.RESULTS: There was significant difference between the average level (1.123±0.108 VS 1.030±0.054, P=0.002) of MMP-2, the ratio (1.050±0.013 VS0.937±0.078, P=0.003) of MMP-2/TIMP-2 in gallbladder carcinomas and in polypoid lesions of the gallbladder. Significant difference was found between the expression of MMP-2 in early stage and advanced tumors, but there was no correlation between MMP-2 protein expression and histological type, differentiation degree, infiltration level, lymph node involvement or liver invasion. Although no difference was observed between TIMP-2 expression and histological type or differentiation degree, signific ant difference was found between TIMP-2 expression and different Nevin stage, infiltration level, local lymph node involvement or liver invasion (1.168±0.067 VS1.048±0.075, 1.170±0.062 vs 1.039±0.06g, 1.039±0.076 VS1.147±0.083, 1.048±0.074 vs 1.103±0.095, P<0.05). MMP-2/TIMP-2 ratio did not correlate with histological type, grade of differentiation and liver invasion, but significant differences were found between MMP-2/TIMP-2 ratio and different Nevin stage, infiltration level and lymph node involvement in patients with carcinoma of gallbladder.CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio could reflect more accurately biological characteristic of gallbladder carcinoma and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis, in

  8. Correlation between MMP-2 and NF-κB expression of intracranial aneurysm

    Institute of Scientific and Technical Information of China (English)

    Wei-Tao Cheng; Ning Wang

    2013-01-01

    Objective: To investigate the correlation between expressions of MMP-2 and NF-κB in the intracranial aneurysm wall, and explore their role in the mechanism of the occurrence, growth and rupture of intracranial aneurysms. Methods: RT-PCR was used to detect the expression of MMP-2 and NF-毷B mRNA of 30 cases of intracranial aneurysm tissue and 10 cases of normal intracranial arterial tissue; Immunohistochemical method was used to detect the expression of MMP-2 and NF-κB protein. Results: The semi-quantitative analysis of MMP-2 and NF-κB in aneurysms tissues and normal tissues were statistically significant different from each other (P<0 05). Immunohistochemical staining results showed NF-κB was expressed in different layers. The expression of them were positive in intimal and medial, and the expression sites were located in the nucleus. MMP-2 were expressed in different layers of the aneurysm wall, and the expressions were positive in media and extima. The MMP-2 and NF-κB-positive expression of aneurysm wall were significantly higher than in normal cerebral arteries (P <0.05). MMP-2 and NF-κB mRNA expression showed positive correlation in the aneurysm wall tissue (r = 0.689, P = 0.005). Conclusions: The expressions of MMP-2 and NF-κB in the intracranial aneurysm wall tissue were significantly higher than in the normal intracranial arterial tissues. They have a synergistic effect on the formation of intracranial aneurysms.

  9. The expressions and significance of MMP-2 and TIMP-2 in human pancreatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    Dong Bo; Ma Qingyong; Li Ming

    2007-01-01

    Objective To study the expressions of MMP-2 and TIMP-2 in pancreatic carcinoma and their relationship with tumor invasion, local metastasis and prognosis of the carcinoma. Methods The expressions of MMP-2 and TIMP-2 were examined in 32 patients with pancreatic carcinomas by S-P immunohistochemical technique and the correlation with pathological tumor parameters were analyzed. Survival analysis was made by using the Kaplan-Meier method. Results The positive rates of MMP-2, TIMP-2 in 32 patients with pancreatic carcinoma were 56.25% and 75.00%, which were significantly higher than those of the controls(P<0.05). Expressions of MMP-2 and TIMP-2 were independent of sex, age, histological grading and type, but well correlated with the lymph node metastasis and TNM clinical staging(Ⅰ and Ⅲ, Ⅱ and Ⅲ). There was a significant association between MMP-2, TIMP-2 and prognosis in pancreatic carcinoma. Conclusion MMP-2 and TIMP-2 might be useful markers for biological aggressiveness of this malignancy and might contribute to the invasive properties of pancreatic carcinoma, which can be used to evaluate the prognosis of patients.

  10. Expression and clinical significance of MMP-2, MVD, MEK-2 in endometriosis

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Qian-Qian Hu; Lu Wang; Meng Shen; Sheng Li

    2016-01-01

    Objective:To investigate the expression and clinical significance of MMP-2, MVD, MEK-2in the endometriosis.Methods:A total of 42 endometrial endometriosis patients with surgery were selected in our hospital obstetrics and gynecology from September 1, 2008 to December 18, 2014. Endometriosis were removed during surgery and served as ectopic group. A total of 42 examples of the above-described patients with endometriosis eutopic were taken out as the eutopic group. Another 34 patients with uterine fibroids were selected in our hospital obstetrics and gynecology during the same period. Normal endometrium were taken as the normal endometrium group. Clinical expression of MMP-2, MVD, MEK-2 of three groups were analyzed.Results:MVD in ectopic endometrium group were significantly higher than those in eutopic and normal endometrium (P<0.05). MEK-2 expression in normal endometrial tissue mainly was negative and weakly positive. The expression was positive in ectopic endometrium and eutopic. The expression of ectopic endometrium MEK-2and MMP-2 were the highest, followed by the reign of endometrium, and the expression of normal endometrium were the lowest.Conclusions: MMP-2, MVD, MEK-2 in ectopic endometrium show high expression, detection of MMP-2, MVD, MEK-2-clinical expression in endometriosis can help in pathogenesis, clinical diagnosis and treatment.

  11. EXPRESSIONS OF STAT3 AND MMP-2 IN CERVICAL CANCER%宫颈癌组织STAT3和MMP-2表达及意义

    Institute of Scientific and Technical Information of China (English)

    李晓蕾; 王霞; 周军红; 赵爱琳

    2011-01-01

    目的 探讨信号转导和转录激活因子3(STAT3)与基质金属蛋白酶-2(MMP-2)在宫颈癌组织表达及意义.方法 采用免疫组织化学SP法分别检测16例正常组织、50例宫颈上皮内瘤变(CIN)、50例宫颈癌组织中STAT3与MMP-2的表达水平.结果 正常宫颈、CIN及宫颈癌组织中STAT3、MMP-2表达水平逐渐增高,各组间差异均有统计学意义(x2=6.417~27.097,P<0.05).STAT3异常表达与宫颈癌的病理分级和临床分期及淋巴结转移有关(x2=4.778~13.651,P<0.05);MMP-2的异常表达与临床分期及淋巴结转移有关(x2=9.039、5.003,P<0.05),而与病理分级无关;两者与病人年龄、肿瘤大小及肿瘤类型均无相关性.宫颈癌组织STAT3与MMP-2的表达呈正相关(r=0.398,P<0.05).结论 宫颈癌组织STAT3与MMP-2表达密切相关,两者表达水平可能与宫颈癌浸润转移有关,STAT3可能通过调控其下游靶基因MMP-2的表达影响宫颈癌的浸润转移.%Objective To investigate the expressions of signal transduction and activators of transcription-3 (STAT3)and matrix metalloproteinase-2 (MMP-2) in cervical cancer and their significance. Methods Immunohistochemical technique was used to detect expressions of STAT3 and MMP-2 in samples of 16 normal cervical tissue, 50 cervical intraepithelial neoplasia (CIN)and 50 cervical cancer. Results The expressions of STAT3 and MMP-2 gradually increased in the order of normal cervical tissue, CIN, and cervical cancer, the differences between the three groups being statistically significant (x2 = 6.417-27.097, P<0.05). The expression of STAT3 was related to clinical stage and pathological grade and lymph node metastasis (x2 = 4.778-13.651,P<0.05) ; and that of MMP-2 was related to clinical stage and lymph node metastasis (x2 = 9.039,5. 003; P<0.05),while no relation to pathological grade. STAT3 and MMP-2 were positively correlated (r=0.398,P<0.05), but these two items were no correlation with patient's age

  12. 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.

  13. 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-expression

  14. 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

  15. MMP-2 Is Mainly Expressed in Arterioles and Contributes to Cerebral Vascular Remodeling Associated with TGF-β1 Signaling.

    Science.gov (United States)

    Hua, Ye; Zhang, Weifeng; Xie, Zhenying; Xu, Nanfei; Lu, Yunnan

    2016-07-01

    There is increasing evidence to suggest that matrix metalloproteinases (MMPs) play a crucial role in vascular remodeling. It has been reported that hypoxia stimulated MMP-9 expression in brain endothelial cells and MMP-9 plays an important role in cerebral vascular remodeling. However, little is known about MMP-2 in the cerebral vessels remodeling. Herein, the aim of this study is to examine the class of vessel and cell type expressing MMP-2 in cerebral vessels and to investigate its potential role in vascular remodeling. In the present study, dual-immunofluorescence assay showed that MMP-2 was mainly expressed in arterioles. In addition, we found that MMP-2 expression in cerebral vessels was derived from endothelial cells, not astrocyte cells. Notably, in the normoxic central nervous system (CNS), there was no effect on vascular development, integrity, or endothelial proliferation when MMP-2 was knocked out, but lack of MMP-2 led to defective arteriolar remodeling and associated with transforming growth factor β1 (TGF-β1) signaling in CNS. Moreover, blocking TGF-β with SB431542, a specific TGF-β inhibitor, significantly reduced the messenger RNA (mRNA) and protein expression levels of MMP-2 in human umbilical vein endothelial cells (HUVECs). Our findings reveal that the level of MMP-2 is high in arteriolar endothelial cells and demonstrate a novel connection between MMP-2 and TGF-β1 signaling in cerebral vascular remodeling.

  16. Prenatal nicotine increases matrix metalloproteinase 2 (MMP-2) expression in fetal guinea pig hearts.

    Science.gov (United States)

    Thompson, Loren P; Liu, Hongshan; Evans, LaShauna; Mong, Jessica A

    2011-11-01

    This study tested the hypothesis that maternal nicotine ingestion increases matrix metalloproteinase (MMP) expression in fetal hearts, which is mediated by the generation of reactive oxygen species. Timed pregnant guinea pigs were administered either water alone, nicotine (200 μg/mL), N-acetylcysteine (NAC), or nicotine plus NAC in their drinking water for 10 days at 52-day gestation (term = 65 days). Near-term (62 days), anesthetized fetuses were extracted, hearts were excised, and left cardiac ventricles snap frozen for analysis of MMP-2/-9/-13 protein and activity levels. Interstitial collagens were identified by Picrosirius red stain to assess changes in the extracellular matrix. Prenatal nicotine increased active MMP-2 forms and interstitial collagen but had no effect on either pro- or active MMP-9 or MMP-13 forms. In the presence of nicotine, NAC decreased active MMP-2 protein levels and reversed the nicotine-induced increase in collagen staining. We conclude that prenatal nicotine alters MMP-2 expression in fetal hearts that may be mediated by reactive oxygen species generation.

  17. 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....

  18. EXPRESSION AND SIGNIFICANCE OF CD 147 AND MMP-2 IN OSTEOSARCOMA%骨肉瘤中CD147、MMP-2的表达和意义

    Institute of Scientific and Technical Information of China (English)

    崔阳; 崔丽嵘; 张涛; 徐志涛; 田跃

    2013-01-01

    目的:探讨骨肉瘤组织CD147、MMP-2蛋白的表达及意义。方法:应用免疫组织化学染色SP法检测37例骨肉瘤及10例骨软骨瘤CD147和MMP-2的表达。结果:骨肉瘤中CD147、MMP-2的阳性表达率均明显高于骨软骨瘤;骨肉瘤中CD147、MMP-2的阳性表达与Enneking分期和肺转移有关,且二者的表达呈正相关(P<0.01)。结论:CD147和MMP-2在骨肉瘤的浸润和转移方面起重要作用,联合检测CD147和MMP-2有望成为判断骨肉瘤预后的新指标。%Objective:To investigate the expression and significance of CD147 and MMP-2 in osteosarcoma. Methods:SP immunohistochemical staining was used to detect the expression of CD147 and MMP-2 in 30 cases osteosarcoma and 10 cases osteochondroma. Results:The positive rate of CD147 and MMP-2 in osteosarcoma were obviously higher than that in osteochondroma. In osteosarcoma, the positive expression of CD147 and MMP-2 had relations with Enneking stage and pulmonary metastasis;moreover, in osteosarcoma, expression of CD147 was positively related with MMP-2. Conclusions:CD147 and MMP-2 play important role in inifltration and metastasis of osteosarcoma. Joint detection of CD147 and MMP-2 is expected to become a new index for judging the prognosis of osteosarcoma.

  19. WISP-1 overexpression upregulates cell proliferation in human salivary gland carcinomas via regulating MMP-2 expression

    Science.gov (United States)

    Li, Fu-Jun; Wang, Xin-Juan; Zhou, Xiao-Li

    2016-01-01

    Background WISP-1 is a member of the CCN family of growth factors and has been reported to play an important role in tumorigenesis by triggering downstream events via integrin signaling. However, little is known about the role of WISP-1 in proliferation of salivary gland carcinoma (SGC) cells. Methods In this study, we investigated the WISP-1 expression in SGC tissues via immunohistochemical staining, Western blotting assay, and real-time quantitative polymerase chain reaction method, and then evaluated the regulatory role of WISP-1 in the growth of SGC A-253 cells. In addition, the role of MMP-2 in the WISP-1-mediated growth regulation was also investigated. Results It was demonstrated that the WISP-1 expression was upregulated at both mRNA and protein levels in 15 of 21 SGC tumor tissues, compared to the non-tumor tissues (five of 21), associated with the lymph node dissection and bone invasion. The in vitro CCK-8 assay and colony-forming assay demonstrated that the exogenous WISP-1 treatment or the WISP-1 overexpression promoted the growth of A-253 cells. In addition, we confirmed that the WISP-1 overexpression upregulated the MMP-2 expression in A-253 cells with the gain-of-function and loss-of-function strategies, and that the MMP-2 knockdown attenuated the WISP-1-mediated growth promotion of A-253 cells. Conclusion We found that WISP-1 was overexpressed in the human SGCs, and the WISP-1 overexpression promoted the salivary gland cell proliferation via upregulating MMP-2 expression. Our study recognized the oncogenic role of WISP-1 in human SGCs, which could serve as a potential target for anticancer therapy. PMID:27799801

  20. Matrix metalloproteinase 2 fused to GFP, expressed in E. coli, successfully tracked MMP-2 distribution in vivo.

    Science.gov (United States)

    Azevedo, A; Prado, A F; Issa, J P M; Gerlach, R F

    2016-08-01

    Matrix Metalloproteinases (MMPs) participate in many physiological and pathological processes. One major limitation to a better understanding of the role MMPs play in these processes is the lack of well-characterized chimeric proteins and characterization of their fluorescence. The specialized literature has reported on few constructs bearing MMPs fused to the sequence of the green fluorescent protein (GFP), but none of the described constructs have been intended for expression in bacteria or for purification and use in vivo. This work has tested a recombinant reporter protein containing the MMP-2 catalytic domain fused to GFP in terms of purification efficiency, degradation of substrates in solution and in zymograms, kinetic activity, GFP fluorescence, and GFP fluorescence in whole animals after injection of the purified and lyophilized fluorescent protein. This work has also characterized rhMMP-2 (recombinant human MMP-2) and inactive clones and used them as negative controls in experiments employing catMMP-2/GFP and rhMMP-2. To our knowledge, this is the first study that has fully characterized a chimeric protein with the MMP-2 catalytic domain fused to GFP, that has efficiently purified such protein from bacteria in a single-step, and that has obtained an adequate chimeric protein for injection in animals and tracking of MMP-2 fate and activity in vivo.

  1. Presence of myofibroblasts and expression of matrix metalloproteinase-2 (MMP-2) in ameloblastomas correlate with rupture of the osseous cortical.

    Science.gov (United States)

    Fregnani, Eduardo Rodrigues; Sobral, Lays M; Alves, Fabio Abreu; Soares, Fernando Augusto; Kowalski, Luis Paulo; Coletta, Ricardo D

    2009-06-01

    Myofibroblasts are frequent in the stroma of neoplasm and by the expression of proteinases they can influence tumor infiltration and progression. In the present study, presence of myofibroblasts and expression of matrix metalloproteinase-2 (MMP-2) and urokinase plasminogen activator (uPA) were examined in intra-osseous solid multicystic ameloblastomas to determine their roles in the clinicopathological features of the tumors. Fifty seven ameloblastomas were analyzed immunohistochemically with antibodies against the isoform alpha of the smooth muscle actin (alpha-SMA), a specific marker of myofibroblasts, MMP-2 and uPA. Myofibroblasts were found in the stroma, in close contact with neoplastic cell islands, of approximately 58% (n = 33) of the ameloblastomas. MMP-2 and uPA were found in the cytoplasm of both neoplastic and stromal cells. A significant correlation between presence of myofibroblasts and MMP-2 expression was observed. Abundant presence of myofibroblast in the stroma of the tumors and expression of MMP-2 in the neoplastic or stromal cells were significantly correlated with rupture of the osseous cortical, which has been considered an important prognostic marker of ameloblastoma aggressiveness. Ours results suggest that abundant presence of myofibroblasts and expression of MMP-2 in solid ameloblastomas may be associated with a more aggressive infiltrative behavior.

  2. 非小细胞肺癌中CD147和MMP2的表达及意义%Expressions of CD 147 and MMP2 in None Small Cell Lung Cancer and its Significance

    Institute of Scientific and Technical Information of China (English)

    王莉; 高爱平

    2012-01-01

    Objective To investigate expressions of CDI47 and MMP2 in none small eell lung eaner and its significance. Method The expressions of CD 147 and MMP2 in 80 eases with none small eelllung eaner and 20 eases with paraneoplastie of the none small cell lung eaner were detected by immimohistoehemieal SP method. Results In 20 specimens with paraneoplastie of the none small cell lung ca ner, the expressions of CDI47 and MMP2 were 20% and 15% ( all P <0. 01 ), The expressions of CDI47 and MMP2 in none small eell lirng eaner were 66. 3% and 70. 0%( all P < 0. 05 ). The expressions of CD147 and MMP2 in none small cell lung caneer were related to elinieal stage and lymph node metastases and not related to tirmor histologieal type and tirmor differentiation. Expression of CD147 was pos itively correlated to MMP2 ( r = 0. 738 ). Conclusion CD147 and MMP2 expressions were high in none small cell lung caner, and they play important roles in caroinogenesis of none small cell lung eaner.%目的 探讨CD147和MMP2在非小细胞肺癌(NSCLC)中的表达及意义.方法 应用免疫组织化学方法SP法检测80例NSCLC及20例癌旁组织中CD147和MMP2的表达情况.结果 CD147和MMP2在20例癌旁组织中阳性表达率分别为20%、15%;CD147、MMP2在NSCLC中的阳性表达率分别为66.3%、70.0%(P均<0.01).CD147和MMP2的表达均与NSCLC患者的临床分期及淋巴结转移相关(P均<0.05),与组织学分型及肿瘤分化程度无关(P均﹥0.05).结论 CD147和MMP2在NSCLC中高表达,两者在NSCLC的发生发展中可能发挥着重要作用.

  3. Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Han-Bin Lin

    2014-01-01

    Full Text Available Matrix metalloproteinases (MMPs significantly contribute to ischemia reperfusion (I/R injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2 in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury.

  4. 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.

  5. 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.

  6. Expression of CD44 and MMP-2: Possible Association with Histopathological Features of Pleuro-Pulmonary Solitary Fibrous Tumors

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    Funda DEMİRAĞ

    2011-05-01

    Full Text Available Objective: Recent studies have shown that tumor cell adhesion molecules CD44 and matrix metalloproteinases (MMP-2 are expressed strongly in many tumors and associated closely with invasion and metastasis of these tumors. Although solitary fibrous tumors (SFT have a good prognosis, a minority behave malignantly. The aim of this study was to analyze the correlation between CD44 and MMP-2 expression with histopathological parameters in SFT.Material and Method: Haemotaxylin-Eosin stained sections of 10 patients with SFT were reexamined for evaluation of histopathological parameters. Immunostaining of CD44 and MMP-2 was performed by using the streptavidin-biotin method with mouse monoclonal antibody.Results: Our cases consisted of three male and seven female patients with a mean age of 54.5 years. Three patients had a history of asbest exposure. Complete resection was performed in 2 malignant (multiple masses and 8 benign SFT cases. One intrapulmonary tumor was treated with pneumonectomy. 3 cases originated from the right and 7 from the left hemithorax. Tumor size ranged from 5 to 27cm. All cases expressed strong CD44. Only 2 malignant SFT and intrapulmonary SFT expressed focal MMP-2.Conclusion: Although MMP-2 positivity was observed in 2 malignant cases, CD44 positivity was not associated with malignancy criteria in solitary fibrous tumors.

  7. Expression of MMP-2,MMP-14 and TIMP-2 in Gastric Cancer and Its Clinical Significance%MMP-2、MMP-14、TIMP-2在胃癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    张金玲; 费雁; 陈伟; 冯刚

    2013-01-01

    Objective To examine the expression of MMP-2, MMP-14 and TIMP-2 in gastric cancer and its clinical significance. Methods The expression of MMP-2,MMP-14 and TIMP-2 was immunohistochemically detected in 80 samples of gastric cancer tissues and 30 adjacent normal gastric tissues. Results The positive expression rate of MMP-2 and MMP-14 was 75.00% and 82. 50% respectively,in gastric cancer tissues,significantly higher than that in normal gastric tissues(36. 67% and 33. 33% ,respectively) (P<0. 01). The positive expression rate of TIMP-2 was 45. 00% and 40. 00% in gastric cancer tissues and normal gastric tissues with no significant difference being found. The expression of MMP-2 and MMP-14 in gastric cancer tissues was closely correlated to the cell differentiation,invasion,lymph node metastasis and TNM stages(P<0. 01). But the expression of TIMP-2 in gastric cancer tissues was only related to the lymph node metastasis (P<0. 05). The expression levels of MMP-2 and MMP-14 were significantly higher in survival time <2 years group than in survival time ≥2 years group(P<0. 01). Conclusion MMP-2 and MMP-14 are over-expressed in gastric cancer. Combined detection for MMP-2/MMP-14 or MMP-2/MMP-14/TIMP-2 may help evaluate the malignancy of gastric cancer and predict the prognosis of patients with gastric cancer.%目的 探讨基质金属蛋白酶(matrix metalloproteinase,MMP)-2、14及基质金属蛋白酶组织抑制因子-2(tissue inhibitor of metalloproteinase,TIMP-2)在胃癌中的表达及其意义.方法 用免疫组织化学方法 (SP法)检测80例胃癌手术患者胃癌组织及30例同期癌旁≥5 cm正常组织中MMP-2、MMP-14及TIMP-2的表达.结果 ①在胃癌、正常胃组织中,MMP-2阳性表达率分别为75.00%和36.67%,MMP-14阳性表达率分别为82.50%和33.33%,差异有统计学意义(均P<0.01);TIMP-2阳性表达率分别为45.00%和40.00%,差异无统计学意义.②癌组织中,MMP-2、MMP-14的表达与肿瘤分化程度、浸润深度、

  8. 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

  9. Regulated Expressions of MMP-2, -9 by Diterpenoids from Euphorbia formosana Hayata

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    Hwa-Wen Yin

    2012-02-01

    Full Text Available Two new abietane type diterpenoids, namely seco-helioscopinolide (1 and 3b,7b-dihydroxy-ent-abieta-8,13-diene-12,16-olide (2 were isolated from the aerial parts of Euphorbia formosana Hayata together with helioscopinolide A (3, helioscopinolide B (4, helioscopinolide C (5 and ent-(5b,8a,9b,10a,12a-12-hydroxyatis-16-ene-3,14-dione (6. The structures of compounds 1−6 were elucidated by analyzing their spectroscopic data and comparison with the literature. Further biological tests by gelatin zymographic analysis revealed that 3−5 significantly up-regulated the expressions and activation of MMP-2 and -9 in human fibrosarcoma cell line HT1080.

  10. 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.

  11. HER2、MMP2、Leptin在结直肠癌组织中的表达及临床意义%Expression and significance of HER2,MMP2 and Leptin intissues of colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    姜友; 刘弋; 葛尔树

    2012-01-01

    Objective To investigate the expression and clinicopathological significance of HER2, MMP2 and Leptin in tissues of colorec-tal carcinoma. Methods The experimental group consisted of 85 cases of colorectal cancer specimens pathologically confirmed. Meanwhile , 85 cases of normal tissues taken from the corresponding area around the cancer were treated as the control group. The immunohisto-chemical SP method was used to detect the expression of HER2, MMP2 and Leptin in carcinomatous tissue and adjacent normal tissue. Results HER2, MMP2 and Leptin positive stained were detected more or less in all of the 85 cases. Positive expression of HER2, MMP2 and Leptin were found 29. 4%( 25/85 ) ,72. 9 %( 62/85 ) and 78. 8%( 67/85 ) in colorectal carcinoma,significantly higher than 7. 1% ( 6/85 ), 16. 5%( 14/85 ) and 20. 0%( 17/85 ) in 85 cases adjacent normal tissues evidently( P <0. 01 ). The expression of HER2, MMP2 and Leptin is positively associated with the depth of tumor invasion, lymph node metastasis and Dukes stage( P < 0.05 ). The postoperative 1 - ,3 - ,5 - year overall survival for positive groups of HER2, MMP2 and Leptin significantly lower than negative groups ( P < 0.05 ). Conclusion MMP2,HER2 and Leptin are significantly expressed in the tissues of colorectal carcinoma ,and closely associated with the growth, invasion and metastasis of tumors. The positive groups of MMP2, HER2 and Leptin have a worse prognosis than the negative groups.%目的 探讨HER2、MMP2和Leptin在结直肠癌组织中的表达及临床意义.方法 选取手术切除并经病理证实的结直肠癌标本85例作为实验组,另取85例相应癌旁正常组织作为对照组.采用免疫组化S-P法测定癌组织、癌旁正常组织中HER2、MMP2和Leptin的表达水平.结果 (1)HER2、MMP2和Leptin在85例结直肠癌组织中均有不同程度的表达:HER2阳性率为29.4%(25/85),MMP2阳性率为72.9 %(62/85),Leptin阳性率为78.8%(67/85)均明显高于85

  12. Expressions and Significances of CD147,OPN and MMP-2 in Oral Squamous Cell Carcinoma%CD147、OPN和MMP-2在口腔鳞状细胞癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    张弛; 满大鹏; 马术明; 曹树文; 李东文

    2012-01-01

    Objective To evaluate the expressions and significances of CD147, OPN and MMP-2 in oral squamous cell carcinoma (OSCC). Methods The expressions of CD147,OPN and MMP-2 were detected by immunohistochemical method (SP) in 35 cases of OSCC. The relationships between the expressions of CD147.OPN and MMP-2 and clinic histopathologic parameters of OSCC were analyzed. Results The expression rates of CD147, OPN and MMP-2 in OSCC tissues were 65. 71%, 71. 43% and 68. 57% respectively. The expressions of CD147, OPN and MMP-2 were positively correlated with tumor histopathologic type, clinical stage and lymph node metastasis (P0. 05). The positive correlations were found among the expressions of CD147,OPN and MMP-2 (MMP-2 and CD147,r=0. 653;MMP-2 and OPN,r=0. 540;CD147 and OPIN,r=0. 381;P<0. 05). Conclusion The expressions of CD147,OPN and MMP-2 increase in OSCC and may be the potential predictor of the malignant degree of OSCC.%目的 研究口腔鳞状细胞癌( OSCC)中基质金属蛋白酶诱导因子(CD147)、骨桥蛋白(OPN)和基质金属蛋白酶-2 (MMP 2)的表达和意义.方法 采用免疫组化SP法对35例OSCC组织中CD147、OPN和MMP-2的表达进行检测,并分析这3个指标间的相关性.结果 CD147、OPN和MMP 2在OSCC组织中高表达,阳性表达率分别为65.71%、71.43%、68.57%;三者的表达均与OSCC病理分级、临床分期和淋巴结转移有关(P<0.05),而与性别、年龄、生长部位无明显相关性(P>0.05);随着病理分级的降低、临床分期的增高和淋巴结转移,三者的阳性表达率均升高;三者之间的表达互呈正相关(MMP-2和CD147,r=0.653;MMP-2和OPN,r=0.540;CD147和OPN,r=0.381;P均<0.05).结论 CD147、OPN和MMP-2的表达与OSCC的病理分级及侵袭转移密切相关.

  13. Survivin和MMP-2在宫颈鳞癌患者中的表达及其临床意义%Expressions and clinical significances of Survivin and MMP-2 in patients with cervical squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    王爱平

    2011-01-01

    目的:探讨Survivin和MMP-2在宫颈鳞癌中的表达及其临床意义.方法:对45例宫颈CINⅠ-Ⅱ、18例宫颈GINⅢ和33例宫颈浸润性鳞癌患者分别进行Survivin和MMP-2检查,比较各组患者的阳性表达,并分析其与宫颈病变级别的相关性.结果:Survivin和MMP-2的阳性表达与宫颈病变的级别呈正相关,不同宫颈病变级别的阳性率比较差异均有统计学意义(P<0.05,P<0.01).结论:临床宫颈病变患者活检后应行Survivin和MMP-2检查,可提示其预后并指导临床治疗.%Objective: To explore the expressions and clinical significances of Survivin and MMP - 2 in patients with cervical squa-mous cell carcinoma Methods: The expression levels of Survivin and MMP -2 in 45 cases with cervical intraepithelial neoplasia (CIN) I ~ II , 18 cases with CINM and 33 cases with invasive cervical squamous cell carcinoma were detected, the positive expression levels of Survivin and MMP - 2 in different groups were compared, its correlation with the degree of cervical lesions was analyzed. Results: There was a positive correlation between the positive expression levels of Survivin and MMP - 2 and the degree of cervical lesions, there was significant difference in the positive expression levels of Survivin and MMP - 2 among cervical lesions of different degrees ( P < 0. 05, P <0. 01) . Conclusion; For the patients with cervical lesions, Survivin and MMP -2 detection should be carried out after biopsy, which can indicate prognosis and direct clinical treatment

  14. 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.

  15. EGF/EGFR 调控 MMP-2在腺样囊性癌中的表达%The Study of EGF/EGFR Induced MMP-2 Expression in Adenoid Cystic Carcinoma

    Institute of Scientific and Technical Information of China (English)

    高杨; 张明; 宫春梅

    2015-01-01

    [ ABSTRACT] Objective To research the regulation of matrix metalloproteinases-2( MMP-2) in adenoid cystic carcinoma which in-duced by EGF/EGFR,and to further explore the mechanisms of the MMP-2 in occurrence,development and metastasis of the adenoid cystic carcinoma.Methods First of all immunohistochemistry was used to observe the expression and distribute of EGFR and MMP-2 in the normal salivary gland and adenoid cystic carcinoma;the real time RT-PCR was used to observe the expression of MMP-2 mRNA in adenoid cystic carcinoma induced by different doses of EGF,then we analysized the expression of MMP-2 mRNA induced by EGF which acted by EGFR in-hibitor;at the last we observed that EGF induced the expression of MMP-2 protein in adenoid cystic carcinoma by western blot.Results Im-munohistochemistry showed that EGFR and MMP-2 have the positive expressions in adenoid cystic carcinoma,while have the negative expres-sions in normal salivary gland;the real time RT-PCR showed that EGF can increase the expression of MMP-2 in adenoid cystic carcinoma,es-pecially in 20μg/L.It also was found that EGFR inhibitor can suppress the increased expression of MMP-2 induced by EGF.The western blot was used to verify that the expression of MMP-2 protein in adenoid cystic carcinoma was induced by EGF.Conclusion The expression of MMP-2 in adenoid cystic carcinoma was induced by EGF,the new theoretical guidance was taken to the clinical treatment of adenoid cystic carcinoma.%目的:通过研究表皮生长因子及其受体(EGF/EGFR)调控基质金属蛋白酶-2(MMP-2)在腺样囊性癌细胞中的表达,为进一步探讨MMP-2在腺样囊性癌发生、发展、转移过程的机制奠定基础。方法应用免疫组织化学SP法检测正常涎腺及腺样囊性癌组织中EGFR和MMP-2的表达分布情况;利用定时定量RT-PCR法检测不同剂量的EGF调控MMP-2 mRNA在腺样囊性癌细胞中的表达水平,分析EGFR阻断剂作用下EGF调控MMP-2 mRNA的表

  16. 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...

  17. 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发展;EMMPRIN可能通过促进MMP

  18. 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

  19. 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.

  20. Changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Lin-Bo Wang; Zhi-Nong Jiang; Miao-Ying Fan; Chao-Yang Xu; Wen-Jun Chen; Jian-Guo Shen

    2008-01-01

    AIM:To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer.METHODS:One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed.Differences in histology of the primary and metastatic gastric cancer were assessed.MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer.RESULTS:Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177)and primary gastric cancer in 75.7% (134/177) of the patients.The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%).MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer,while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer.CONCLUSION:Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer.This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.

  1. Supraglottic carcinoma CT and c-Met、the relationship of the expression of MMP-2%声门上型喉癌CT表现与c-Met、MMP-2表达的关系

    Institute of Scientific and Technical Information of China (English)

    王乐秋; 蔡胜艳; 张建波; 郝艳坤; 隋萍萍

    2012-01-01

      目的探讨c-Met和MMP-2在人声门上型喉癌组织中的表达与其CT的关系.方法收集48例声门上型喉癌患者的CT图像及癌组织标本,分别采用原位杂交方法检测其c-Met基因及用免疫组化法检测MMP-2基因,分析检测结果与CT图像的关系.结果声门上型喉癌原发灶不同范围的c-Met、MMP-2基因表达差异无显著意义(P>0.05).而CT显示有无侵袭会厌前间隙、会厌谷、梨状窝、喉咽侧壁、声带以及有无颈淋巴结转移各组中c-Met、MMP-2基因的表达差异有显著性(P0.05).But CT showed no invasion preepiglottic space, epiglottic val ecula, piriform fossa, hypopharyngeal side wal , vocal and without cervical lymph node metastasis in groups c-Met, MMP-2gene expression differences are significant (P<0.05). Conlusion C-Met, MMP-2 abnormal gene expression in laryngeal cancer cel proliferation, development and play an important role in metastasis, its expression and supraglottic carcinoma invasion and metastasis is closely related to carcinoma of the supraglottic larynx, can be a sign of a poor prognosis.

  2. Claudin-1和MMP-2在视网膜母细胞瘤中表达及其相关性%The expression and correlation of Claudin-1 and MMP-2 in retinoblastoma

    Institute of Scientific and Technical Information of China (English)

    杨洋; 邬黎青; 程波; 雷浪

    2013-01-01

    目的:探讨Claudin-1和MMP-2蛋白在视网膜母细胞瘤中的表达变化及其与视网膜母细胞瘤组织分化、视神经浸润和临床分期的相关性。方法采用免疫组化方法(MaxVisionTM)检测Claudin-1、MMP-2蛋白在45例视网膜母细胞瘤和15例正常视网膜组织石蜡标本的表达,运用卡方检验和Spearman等级相关检验分析Clandin-1和MMP-2在视网膜母细胞瘤组织中表达的相关性。结果(1)Claudin-1蛋白在视网膜母细胞瘤组织阳性表达明显低于在正常视网膜组织;在分化型组阳性表达显著高于未分化型组,P=0.015;在未侵犯视神经组阳性表达明显高于侵犯视神经组,P<0.001;在临床Ⅰ期、Ⅱ期、Ⅲ期组中各组间表达均具有统计学差异,P<0.01;不同性别组中Claudin-1表达没有统计学差异,P=0.661。(2)MMP-2蛋白在视网膜母细胞瘤中阳性表达明显高于正常视网膜组织细胞;在分化型组阳性表达中表达低于未分化型组,表达没有统计学差异,P=0.636;在侵犯视神经组阳性表达明显高于未侵犯视神经组,P=0.011;在临床Ⅰ期组、Ⅱ期和Ⅲ期各期之间中表达均具有统计学差异,P<0.05;在不同性别组中表达没有统计学差异,P=0.58。(3)在视网膜母细胞瘤中Claudin-1表达下降和MMP-2表达上升两者呈负相关(r=-0.537,P=0.023)。结论 Claudin-1表达水平与视网膜母细胞瘤细胞分化、视神经浸润和临床分期呈正相关;MMP-2表达水平与视网膜母细胞瘤视神经浸润和临床分期呈负相关。Clandin-1和MMP-2在视网膜母细胞瘤的视神经浸润与肿瘤发展起相反作用。%Objective To study the protein expression of Claudin-1 and MMP-2 protein in retinoblastoma and their correla-tion with retinoblastoma tissue differentiation,clinical optic nerve infiltration capacity and retinoblastoma staging. Methods Im-munohistochemistry was used to analyze the expression of

  3. 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.

  4. Limited independent prognostic value of MMP-14 and MMP-2 expression in ovarian cancer

    NARCIS (Netherlands)

    Vos, M.C.; Wurff, A.A. van der; Bulten, J.; Kruitwagen, R.; Feijen, H.; Kuppevelt, T.H. van; Hendriks, T.; Massuger, L.F.

    2016-01-01

    BACKGROUND: In cancer, various MMPs play a role in progression and metastasis and their overexpression generally indicates a poor prognosis. MMP-14 is the main activator of MMP-2 and both molecules play a role in normal ovarian follicular development. Earlier reports indicated a prognostic value for

  5. Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients.

    Science.gov (United States)

    Groblewska, Magdalena; Mroczko, Barbara; Gryko, Mariusz; Pryczynicz, Anna; Guzińska-Ustymowicz, Katarzyna; Kędra, Bogusław; Kemona, Andrzej; Szmitkowski, Maciej

    2014-04-01

    The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients' survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.

  6. 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

  7. 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

  8. 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.

  9. Expression of RECK gene in the osteosarcoma cell line and its correlation with MMP-2%RECK基因在骨肉瘤细胞中的表达及其与MMP-2的关系

    Institute of Scientific and Technical Information of China (English)

    Liang Xu; Shuhua Yang; Guanjun Liu; Junhong Guo

    2009-01-01

    Objective:To detect the expression of RECK gene in the highly and low metastatic cell sublines of human os-teosarcema cell HOS and explore its possible roles on the occurrence and metastasis of osteosarcoma. Methods:RT-PCR, gelatin zymography, and rnatrigel invasion assay were respectively used to evaluate the endogenous expression of RECK mRNA, MMP-2 activation ratio and invesive capacity in the two osteosarcoma cell sublines. Results:The highly metastatic cell group expressed significantly lower mRNA level of RECK than the low metastatic cell group (P < 0.05), but showed higher MMP-2 activation ratio and invasive capacity (P < 0.05 and P < 0.01, respectively). Conclusion:The abnormal low expression of RECK may participate in osteosarcoma invasion and metastasis, and may be a new therapeutic target for osteosarooma.

  10. Increased expression of matrix metalloproteinase-2 (MMP-2) predicts tumour recurrence and unfavourable outcome in non-small cell lung cancer.

    Science.gov (United States)

    Leinonen, Tero; Pirinen, Risto; Böhm, Jan; Johansson, Risto; Kosma, Veli-Matti

    2008-06-01

    The purpose of this study was to analyse the expression of matrix metalloproteinase-2 (MMP-2) and its extracellular matrix metalloproteinase inducer (EMMPRIN) in non-small cell lung cancer (NSCLC), and to evaluate their significance to predict tumour behaviour. The study consists of 212 patients treated by the resection of the tumour. Tumour samples were stained immunohistochemically, and the expression of MMP-2 and EMMPRIN was evaluated both in tumour cells and in peritumoural stromal tissue. The results were compared with clinicopathological factors and survival of the patients. High expression of MMP-2 in tumour cells was found in 83 out of 191 cases (44%). Adenocarcinomas showed more often high expression of MMP-2 as compared with squamous cell or large cell carcinomas (p=0.001). High cancer cell associated MMP-2 expression was associated with increased tumour recurrence (p=0.001). Tumour stroma showed positive staining in 162 (98%) cases and was considered highly stained in 120 (72%) cases. The high stromal MMP-2 expression was noticed more often among large cell carcinomas as compared with other histological types (p=0.007). High cancer cell associated EMMPRIN expression was found in 115 (61%) cases and was associated only with high MMP-2 expression in tumour cells (p=0.006). In overall survival (OS) and disease free survival (DFS) analyses, type of tumour (p=0.001 and p=0.0004), advanced stage (p=0.001 and p=0.013) and high MMP-2 expression in tumour cells (p=0.018 and p=0.001) were associated with poor survival. Also, high stromal MMP-2 expression was related to poor outcome in both OS and DFS analyses (p=0.010 and 0.045, respectively). In multivariate analysis, stromal MMP-2 expression retained its prognostic value to predict OS and DFS (p=0.028 and p=0.039, respectively), together with tumour type and stage (p=0.017, p=0.001 and p=0.021, p=0.008, respectively). The present study shows the significant prognostic value of MMP-2 in NSCLC suggesting that the

  11. 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.

  12. Expression and Clinical Significance of CD147 and MMP-2 
in Squamous Cell Carcinoma and Adenocarcinoma of the Lungs

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    Siwen WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that CD147 was an extracellular matrix metalloproteinase inducer reportedly involved in the invasion and metastasis of malignancies. The aim of this study is to investigate CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs and to analyze their clinical significance. Methods Tissue samples from 55 patients with squamous cell carcinoma and adenocarcinoma of the lungs and their corresponding non-cancerous tissues were examined for CD147 and MMP-2 expression using immunohistochemistry. Results The positive expression rates of CD147 and MMP-2 in the squamous cell carcinoma and adenocarcinoma among the lung tissues were significantly higher than those in the corresponding normal lung tissues. Moreover, the CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs were related to lymph node metastasis and TNM stages (P<0.05, but not to age, gender and histologic type (P>0.05. MMP-2 expression was highly correlated with CD147 expression. Conclusion CD147 and MMP-2 expression is correlated with the invasion and metastasis of squamous cell carcinoma and adenocarcinoma of the lungs and may be used as objective markers for predicting the behavior of squamous cell carcinoma and adenocarcinoma of the lungs.

  13. Dimerization of matrix metalloproteinase-2 (MMP-2): functional implication in MMP-2 activation.

    Science.gov (United States)

    Koo, Bon-Hun; Kim, Yeon Hyang; Han, Jung Ho; Kim, Doo-Sik

    2012-06-29

    Matrix metalloproteinase-2 (MMP-2) functions in diverse biological processes through the degradation of extracellular and non-extracellular matrix molecules. Because of its potential for tissue damage, there are several ways to regulate MMP-2 activity, including gene expression, compartmentalization, zymogen activation, and enzyme inactivation by extracellular inhibitors. Enzyme regulation through zymogen activation is important for the regulation of MMP-2 activity. In our previous studies, we showed that thrombin directly cleaved the propeptide of MMP-2 at specific sites for enzyme activation. We also demonstrated that heparan sulfate was required for thrombin-mediated activation of pro-MMP-2 by binding to thrombin, presumably through conformational changes at the active site of the enzyme. This suggests a regulatory mechanism for thrombin-mediated activation of pro-MMP-2. In this study, we found that MMP-2 formed a reduction-sensitive homodimer in a controlled manner and that Ca(2+) ion was essential for homodimerization of MMP-2. Homodimerization was not associated with protein kinase C-mediated phosphorylation of MMP-2. MMP-2 formed a homodimer through an intermolecular disulfide bond between Cys(102) and the neighboring Cys(102). Homodimerization of MMP-2 enhanced thrombin-mediated activation of pro-MMP-2. Moreover, the MMP-2 homodimer could cleave a small peptide substrate without removal of the propeptide. Taken together, our experimental data suggest a novel regulatory mechanism for pro-MMP-2 activation that is modulated through homodimerization of MMP-2.

  14. Histone deacetylase (HDAC) 10 suppresses cervical cancer metastasis through inhibition of matrix metalloproteinase (MMP) 2 and 9 expression.

    Science.gov (United States)

    Song, Chenlin; Zhu, Songcheng; Wu, Chuanyue; Kang, Jiuhong

    2013-09-27

    Aberrant expression of histone deacetylases (HDACs) is associated with carcinogenesis. Some HDAC inhibitors are widely considered as promising anticancer therapeutics. A major obstacle for development of HDAC inhibitors as highly safe and effective anticancer therapeutics is that our current knowledge on the contributions of different HDACs in various cancer types remains scant. Here we report that the expression level of HDAC10 was significantly lower in patients exhibiting lymph node metastasis compared with that in patients lacking lymph node metastasis in human cervical squamous cell carcinoma. Forced expression of HDAC10 in cervical cancer cells significantly inhibited cell motility and invasiveness in vitro and metastasis in vivo. Mechanistically, HDAC10 suppresses expression of matrix metalloproteinase (MMP) 2 and 9 genes, which are known to be critical for cancer cell invasion and metastasis. At the molecular level, HDAC10 binds to MMP2 and -9 promoter regions, reduces the histone acetylation level, and inhibits the binding of RNA polymerase II to these regions. Furthermore, an HDAC10 mutant lacking histone deacetylase activity failed to mimic the functions of full-length protein. These results identify a critical role of HDAC10 in suppression of cervical cancer metastasis, underscoring the importance of developing isoform-specific HDAC inhibitors for treatment of certain cancer types such as cervical squamous cell carcinoma.

  15. 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.

  16. 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.

  17. 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.

  18. Green tea polyphenol epigallocatechin-3-gallate suppresses rat hepatic stellate cell invasion by inhibition of MMP-2 expression and its activation

    Institute of Scientific and Technical Information of China (English)

    Mao-chuan ZHEN; Xiao-hui HUANG; Qian WANG; Kai SUN; Yun-jian LIU; Wen LI; Long-Juan ZHANG; Liang-qi CAO; Xi-ling CHEN

    2006-01-01

    Aim: Epigallocatechin-3-gallate (EGCG) is the major component of green tea polyphenols, whose wide range of biological properties includes anti-fibrogenic activity. Matrix metalloproteinases (MMP) that participate in extracellular matrix degradation are involved in the development of hepatic fibrosis. The present study investigates whether EGCG inhibits activation of the major gelatinase matrix metalloproteinase-2 (MMP-2) in rat hepatic stellate cells (HSC). Methods: The expression of MMP-2, tissue inhibitors of metalloproteinases-2 (TIMP-2), and membrane-type 1-MMP (MT1-MMP) was assessed by RT-PCR and Western blot analyses. MMP-2 activity was evaluated by zymography and MT1-MMP activity was assessed by an enzymatic assay. HSC migration was measured by a wound healing assay and cell invasion was performed using Transwell cell culture chambers. Results: The expression of MMP-2 mRNA and protein in HSC was substantially reduced by EGCG treatment. EGCG treatment also reduced con-canavalin A (ConA)-induced activation of secreted MMP-2 and reduced MT1-MMP activity in a dose-dependent manner. In addition, EGCG inhibited either HSC migration or invasion. Conclusion: The abilities of EGCG to suppress MMP-2 activation and HSC invasiveness suggest that EGCG may be useful in the treatment and prevention of hepatic fibrosis.

  19. Angiotensin II induces an increase in MMP-2 expression in idiopathic ascending aortic aneurysm via AT1 receptor and JNK pathway.

    Science.gov (United States)

    Wang, Chunmao; Chang, Qian; Qian, Xiangyang; Tian, Chuan; Sun, Xiaogang

    2015-07-01

    The cellular and molecular mechanisms responsible for human idiopathic ascending aortic aneurysm (IAAA) remain unknown. Matrix metalloproteinase-2 (MMP-2) is a key enzyme for the degradation of extracellular matrix in aneurysmal walls. The aim of this study was to elucidate the role of the angiotensin II (Ang II) pathway in MMP-2 induction in IAAA aortic walls. Quantitative polymerase chain reaction and western blot analysis were used to compare the MMP-2 mRNA and protein levels in ascending aortic specimens with those in IAAA patients (n = 10) and heart transplant donors (n = 5) without any aortopathy. It was found that MMP-2 expression was significantly increased, which was associated with elastic lamellae disruption in IAAA walls. Additionally, the expression levels of angiotensinogen (AGT) and Ang II in the ascending aortic tissues from individuals with and without IAAAs were detected by western blot analysis and radioimmunoassay, respectively. The results demonstrated that the expressions of AGT and Ang II protein were significantly increased in the ascending aortic tissues of IAAA patients. Furthermore, whether Ang II induces MMP-2 expression was investigated using human IAAA walls ex vivo culture. It was found that exogenous Ang II increased the MMP-2 expression in a dose-dependent manner, which was completely inhibited by the Ang II type 1 receptor (AT1R) inhibitor candesartan and was mediated by c-Jun N-terminal kinase (JNK) activation. Taken together, these results indicate that Ang II can induce an increase of MMP-2 expression via AT1R and JNK in ex vivo cultured IAAA aortic walls, and suggest that angiotensin receptor blocker (ARB) drugs and JNK inhibitors have the potential in the prevention or treatment of IAAAs.

  20. Expression and clinical significance of Shh,Gli-1 and MMP-2 in gastric cancer%SHH、Gli-1、MMP-2在胃癌组织中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    陈世豪; 唐源; 卞永生

    2016-01-01

    目的:探讨胃癌组织中刺猬信号通路(Hedgehog signaling pathway,Hh)中的音猬因子(Sonic hedgehog,Shh)和胶质瘤相关癌基因同源物-1(Glioma-associated oncogene homolog -1,Gli-1)与金属基质蛋白酶-2(Matrix metalloproteinase-2,MMP-2)的表达和临床意义。方法采用免疫组织化学方法检测40例人胃癌组织、人胃息肉组织和40例正常胃黏膜组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2蛋白的表达。结果胃癌组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2的阳性表达率分别为62.5%、67.5%、72.5%,高于胃息肉组织(阳性表达率分别为27.5%、37.5%、32.5%)和正常胃黏膜组织(阳性表达率分别为22.5%、17.5%、12.5%)(P<0.05);以上三者的表达与患者性别、年龄、组织学类型无关(P>0.05);而与分化程度、浸润深度、淋巴结转移相关(P<0.05);音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2表达呈正相关。结论刺猬信号通路可能通过某些机制可上调金属基质蛋白酶-2的表达,从而增强胃癌的侵袭性。联合检测胃癌组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2的表达水平在一定程度上可以作为胃癌预后的客观参考指标。%Objective To investigate the expression and clinical significance of Sonic hedgehog (Shh),Glioma-asso-ciated oncogene homolog-1 (Gli-1)and Matrix metalloproteinase-2 (MMP-2)in gastric cancer.Shh and Gli-1 are the molecules of Hedgehog (Hh)signaling pathway. MMP-2 is the member of matrix metalloproteinase family. Methods The expression of Shh,Gli-1 and MMP-2 proteins was examined by immunohistochemistry in the human gastric cancer tissues and the human gas-tric polyp and the normal gastric mucosa tissues of 40 cases. Results The positive expression rates of Shh,Gli-1 and MMP-2

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

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    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.

  2. The expression and clinical significance of the CD147 and MMP-2 mRNA in gastric carcinoma%CD147、MMP-2mRNA在胃癌组织中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    赖丽琴; 张红; 吴倩; 秦蓉

    2011-01-01

    Objective To investigate the significance of CD147 and matrix metalloproteinase -2 ( MMP-2 ) mRNA expression in human gastric carcinoma. Methods CD147 and MMP-2 mRNA expression was assessed in paraffinembedded specimens collected from 76 cases of gastric carcinoma and 20 cases of adjacent normal tissues by in situ hybridization methods. Results The positive rate of expression of CD147 and MMP-2 mRNA in gastric carcinoma was 69. 7%.75.0%, respectively. The expression of CD147 and MMP-2 mRNA was both strongly related to the tumor size,depth of invasion and lymph nodes metastasis of gastric carcinoma( P<0. 05 ). However.CD147 and MMP-2 mRNA had no significant difference with pathological grades, age and gender. There was a significant relationship between expressions of CD147 and MMP-2 mRNA ( P <0. 01 ). Conclusion CD147 and MMP-2 play an important role in the invasion and metastasis in gastric carcinoma. They might be good markers for development and prognosis of gastric carcinoma.%目的 探讨CD147及基质金属蛋白酶-2(MMP-2)mRNA在胃癌组织中的表达及其意义.方法 应用原位杂交方法检测76例石蜡包埋胃癌组织及20例癌旁正常胃黏膜中CD147和MMP-2 mRNA的表达情况.结果 CD147和MMP-2 mRNA在胃癌组织中的阳性表达率分别为69.7%、75.0%,与癌旁正常胃黏膜比较差异均有统计学意义(P<0.01).CD147和MMP-2 mRNA阳性表达与肿瘤的大小、浸润深度、淋巴结转移有关(P<0.05),与患者的性别、年龄、肿瘤的分化程度无关.CD147和MMP-2 mRNA在胃癌组织中的表达具有相关性(P<0.01).结论 CD147和MMP-2 mRNA的表达与胃癌的浸润和转移有关,可以作为胃癌进展和预后的指标.

  3. CD147和MMP-2、VEGF在原发性肝癌的表达及意义%Expression and significance of CD147 and MMP- 2、VEGF protein in primary hepatocarcinoma

    Institute of Scientific and Technical Information of China (English)

    王利霞; 楼善贤; 沈蔚

    2005-01-01

    目的探讨CD147和MMP-2、VEGF在原发性肝癌进展过程中的作用及其相互关系,为从免疫学范畴治疗肝癌提供依据.方法用免疫组化EnVision二步法检测40例原发性肝癌CD147和MMP-2、VEGF蛋白的表达情况,结合临床病理资料进行分析.结果 CD147和MMP-2、VEGF在原发性肝癌的阳性表达率分别为87.5%,77.5%,75.0%,MMP-2在转移组表达显著增高(P<O.05),CD147和MMP-2、VEGF的表达与肿瘤直径有关,当直径<3cm时表达显著降低(P<0.01),CD147和MMP-2、VEGF间的表达呈正相关.结论 CD147和MMP-2、VEGF可能是原发性肝癌恶性进展的重要因素,CD147刺激MMP-2进而产生VEGF,是原发性肝癌免疫治疗的潜在靶位.

  4. Salinomycin causes migration and invasion of human fibrosarcoma cells by inducing MMP-2 expression via PI3-kinase, ERK-1/2 and p38 kinase pathways.

    Science.gov (United States)

    Yu, Seon-Mi; Kim, Song Ja

    2016-06-01

    Salinomycin (SAL) is a polyether ionophore antibiotic that has recently been shown to regulate a variety of cellular responses in various human cancer cells. However, the effects of SAL on metastatic capacity of HT1080 human fibrosarcoma cells have not been elucidated. We investigated the effect of SAL on migration and invasion, with emphasis on the expression and activation of matrix metalloproteinase (MMP)-2 in HT1080 human fibrosarcoma cells. Treatment of SAL promoted the expression and activation of MMP-2 in a dose- and time-dependent manner, as detected by western blot analysis, gelatin zymography, and real-time polymerase chain reaction. SAL also increased metastatic capacities, as determined by an increase in the migration and invasion of cells using the wound healing assay and the invasion assay, respectively. To confirm the detailed molecular mechanisms of these effects, we measured the activation of phosphoinositide 3 kinase (PI3-kinase) and mitogen-activated protein kinase (MAPK)s (ERK-1/2 and p38 kinase), as detected by the phosphorylated proteins through western blot analysis. SAL treatment increased the phosphorylation of Akt and MAPKs. Inhibition of PI3-kinase, ERK-1/2, and p38 kinase with LY294002, PD98059, and SB203580, respectively, in the presence of SAL suppressed the metastatic capacity by reducing MMP-2 expression, as determined by gelatin zymography. Our results indicate that the PI3-kinase and MAPK signaling pathways are involved in migration and invasion of HT1080 through induction of MMP-2 expression and activation. In conclusion, SAL significantly increases the metastatic capacity of HT1080 cells by inducing MMP-2 expression via PI3-kinase and MAPK pathways. Our results suggest that SAL may be a potential agent for the study of cancer metastatic capacities.

  5. Pulsatile ex vivo perfusion of human saphenous vein grafts under controlled pressure conditions increases MMP-2 expression

    Directory of Open Access Journals (Sweden)

    Lange Rüdiger

    2011-07-01

    Full Text Available Abstract Background The use of human saphenous vein grafts (HSVGs as a bypass conduit is a standard procedure in the treatment of coronary artery disease while their early occlusion remains a major problem. Methods We have developed an ex vivo perfusion system, which uses standardized and strictly controlled hemodynamic parameters for the pulsatile and non-static perfusion of HSVGs to guarantee a reliable analysis of molecular parameters under different pressure conditions. Cell viability of HSVGs (n = 12 was determined by the metabolic conversion of 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT into a purple formazan dye. Results Under physiological flow rates (10 mmHg HSVGs remained viable for two weeks. Their exposure to arterial conditions (100 mmHg was possible for one week without important reduction in viability. Baseline expression of matrix metalloproteinase-2 (MMP-2 after venous perfusion (2.2 ± 0.5, n = 5 was strongly up-regulated after exposure to arterial conditions for three days (19.8 ± 4.3 or five days (23.9 ± 6.1, p Conclusion Therefore, our system might be helpful to more precisely understand the molecular mechanisms leading to an early failure of HSVGs.

  6. 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

  7. Expression of VEGF,MMP-2 and MVD in prostatic cancer and its relation to clinicopathology%前列腺癌VEGF与MMP-2表达和微血管密度的临床病理关系

    Institute of Scientific and Technical Information of China (English)

    吴健; 张昶

    2009-01-01

    目的:探讨血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)和微血管密度(MVD)与前列腺癌的相关性.方法:应用免疫组织化学方法检测48例前列腺癌组织和20例前列腺增生组织VEGF和MMP-2蛋白的表达并计数微血管密度.结果:前列腺癌组织中VEGF、MMP-2的阳性表达率和MVD值显著高于前列腺增生组织(P<0.01),VEGF、MMP-2的阳性表达率和MVD值与前列腺癌TNM分期和骨转移情况具有相关性(P<0.05),前列腺癌VEGF、MMP-2的阳性表达率和MVD值呈正相关(P<0.01).结论:VEGF、MMP-2的高表达和MVD增高在前列腺癌发生发展中具有重要作用,检测VEGF、MMP-2和MVD对判断前列腺癌的预后具有重要意义.

  8. CTGF对体外人晶状体上皮细胞表达MMP-2、TIMP-2的影响%Effect of CTGF on Expression of MMP-2 ,TIMP-2 of Human Lens Epithelial Cells Incubated in vitro

    Institute of Scientific and Technical Information of China (English)

    谢伟英; 徐国兴

    2013-01-01

    目的 研究结缔组织生长因子(CTGF)对体外培养人晶状体上皮细胞(HLECs)基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶抑制剂-2(TIMP-2)表达的影响.方法 采用免疫细胞化学染色法及反转录-聚合酶链反应(RT-PCR)法检测不同浓度CTGF对HLECs诱导MMP-2及TIMP-2的表达.结果 在无CTGF刺激的情况下,HLECs基本不表达MMP-2及TIMP-2;随着CTGF浓度增加,HLECs表达MMP-2增加,并且这种作用随浓度的增加而增强,每两组之间的比较差异均有统计学意义(P<0.01或P<0.05);对TIMP-2的表达无明显影响(P>0.05).结论 CTGF能诱导HLECs表达MMP-2,对HLECs表达TIMP-2无影响;MMP-2/TIMP-2的比例失调,引起ECM的代谢紊乱,可能是后发性白内障的发病机制之一.%Objective To investigate the effect of connective tissue growth factor( CTGF) on the expression of matrix metalloprotein-ases -2(MMP -2) and tissue inhibitor of matrix metalloproteinases -2(TIMP -2) of human lens epithelial cells(HLECs) in vitro,thus to evaluate the role of CTGF in the pathogenesis of post - cataract. Methods The expression of MMP - 2 and TIMP - 2 was detected by immunocytochemical stain and RT - PCR when HLECs were incubated for 24h. Results In a dose - dependent manner,CTGF increased MMP -2 mRNA and protein expression in HLECs(P 0. 05 ) . Conclusion CTGF can induce the expression of MMP - 2 in HLECs, but has no effect on TIMP - 2. This leads to in balance between MMP -2 and TIMP -2. This might be an important pathway leading to post - cataract.

  9. Sphingosine-1-phosphate induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in endothelial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Chi-hao CHANG; Yuan-li HUANG; Ming-kwang SHYU; Shee-uan CHEN; Chih-hsin LIN; Tsai-kai JU; JenHer LU

    2013-01-01

    Aim:To investigate whether sphingosine-1-phosphate (S1P),a potent angiogenic factor,induced vascular endothelial growth factor-C (VEGF-C) expression in endothelial cells in vitro and to examine its underlying mechanisms.Methods:Human umbilical vein endothelial cells (HUVECs) were examined.VEGF-C mRNA expression in the cells was assessed using real-time PCR.VEGF-C protein and FGFR-1 phosphorylation in the cells were measured with ELISA.RNA interference was used to downregulate the expression of matrix metalloproteinase-2 (MMP-2),fibroblast growth factor-1(FGF-1) and FGF receptor-1 (FGFR-1).Results:Incubation of HUVECs with S1P (1,5,and 10 μmol/L) significantly increased VEGF-C expression.The effect was blocked by pretreatment with the MMP inhibitor GM6001 or the FGFR inhibitor SU5402,but not the EGFR inhibitor AG1478.The effect was also blocked in HUVECs that were transfected with FGFR-1 or MMP-2 siRNA.Furthermore,incubation of HUVECs with S1P (5 μmol/L) significantly increased FGFR-1 phosphorylation,which was blocked by GM6001.Moreover,knockdown of FGF-1,not FGF-2,in HUVECs with siRNAs,blocked S1P-induced VEGF-C expression.Conclusion:S1P induces VEGF-C expression through a MMP-2/FGF-1/FGFR-1-dependent pathway in HUVECs.

  10. The Expression of CD147 and MMP-2 in Human Early Esophageal Carcinoma%CD147和MMP-2在早期食管癌中的表达

    Institute of Scientific and Technical Information of China (English)

    刘海明; 窦俊峰

    2010-01-01

    目的 探讨CD147和MMP-2在食管癌发生过程中的作用及其相关性.方法 应用免疫组织化学S-P法检测CD147和MMP-2在19例食管早期癌和20例正常食管黏膜标本中的表述.结果 CD147和MMP-2在早期癌中的表达均高于正常食管黏膜(P<0.05)CD147和MMP-2可能与食管癌的发生有关,他们的变化可能是食管癌发生中的早期事件.

  11. 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.

  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. MMP-2及MMP-7在食管癌及癌旁组织中的表达%Expressions of MMP-7 and MMP-2 in esophageal cancer patients

    Institute of Scientific and Technical Information of China (English)

    孙晓宏; 庞作良; 罗洞波

    2010-01-01

    目的 探讨MMP-7和MMP-2在食管癌中的表达及其相互关联.方法 采用RT-PCR方法检测MMP-7和MMP-2在60例食管癌组织及其相应癌旁组织中的表达.结果 MMP-7和MMP-2在癌组织中阳性率分别为90.0%(54/60)和91.7%(55/60),在其对应癌旁组织中的阳性率为48.3%(29/60)和65.0%(39/60).通过RT-PCR半定量分析癌组织及其相应的癌旁组织中MMP-7和MMP-2的表达量,差异有统计学意义(P<0.05).MMP-7的表达与肿瘤浸润深度及淋巴结转移有关(P<0.05).MMP-2与MMP-7表达呈正相关.结论 MMP-7和MMP-2的表达可能与食管癌的早期进展和程度有关.

  14. 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

  15. Temporal and spatial expression of MMP-2, -9, -14 and their inhibitors TIMP-1, -2, -3 in the corpus luteum of the cycling rhesus monkey

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The corpus luteum (CL) is a transient endocrine organ that secretes progesterone to support early pregnancy. If implantation is unsuccessful, luteolysis is initiated. Extensive tissue remodeling occurs during CL formation and luteolysis. In this study, we have studied the possible involvement of MMP-2, -9, -14, and their inhibitors, TIMP-1, -2, -3 in the CL of cycling rhesus monkey at various stages by in situ hybridization, immunohistochemistry and microscopic assessment. The results showed that the MMP-2 mRNA and protein were mainly expressed in the endothelial cells at the early and middle stages of the CL development, while their expressions were observed in the luteal cells at the late stage during luteal regression. MMP-9 protein was detected in the CL at the early and middle stages, and obviously increased at the late stage. The expressions of MMP-14 and TIMP-1 mRNA were high at the early and late stages, and low at the middle stage. TIMP-2 mRNA was high throughout all the stages, the highest level could be observed at the late stage. The TIMP-3 production was detected throughout all the stages, but obviously declined during CL regression. MMP-9, -14 and TIMP-1, -2, -3 were mainly localized in the cytoplasm of the steroidogenic cells. The results suggest that the MMP/TIMP system is involved in regulation of CL development in the primate, and the coordinated expression of MMP-2, -14 and TIMP-1, -3 may have a potential role in the CL formation and the functional maintaining, while the interaction of MMP-2, -9, -14 and TIMP-1, -2, -3 might also play a role in CL regression at the late stage of CL development in the primate.

  16. Genistein Suppression of Matrix Metalloproteinase 2 (MMP-2) and Vascular Endothelial Growth Factor (VEGF) Expression in Mesenchymal Stem Cell Like Cells Isolated from High and Low Grade Gliomas

    Science.gov (United States)

    Yazdani, Yasaman; Sharifi Rad, Mohammad Reza; Taghipour, Mousa; Chenari, Nooshafarin; Ghaderi, Abbas; Razmkhah, Mahboobeh

    2016-12-01

    Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted.

  17. Annexin A2、MMP-2在宫颈浸润癌组织中的表达及意义%Expressions of Annexin A2 and MMP-2 protein in invasive cervical cancer

    Institute of Scientific and Technical Information of China (English)

    杜文升

    2011-01-01

    目的:探讨钙磷脂结合蛋白A2(Annexin A2)、基质金属蛋白酶2(matrix metalloproteinases 2,MMP-2)蛋白在宫颈浸润癌(invasive cervical carcinoma,ICC)、宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及慢性宫颈炎(chronic cervicitis,CCS)组织中的表达及意义.方法:采用免疫组织化学SP法检测34例ICC、20例CIN及20例CCS组织中Annexin A2、MMP-2蛋白的表达情况,并分析其与临床病理特征的关系.结果:(1)Annexin A2、MMP-2在ICC组的阳性表达率显著高于CIN、CCS组;Annexin A2、MMP-2在CIN组的表达明显高于CCS组;(2)Annexin A2的表达与病理分级及淋巴结转移呈正相关(P<0.05);MMP-2与病理分级显著相关(P<0.05);(3)Annexin A2、MMP-2在ICC中的表达二者呈正相关(r=0.610,P<0.01).结论:Annexin A2、MMP-2在宫颈癌的发生发展中可能起重要作用,并为宫颈癌的早期诊断提供可能的理论依据.

  18. IL-21 R、MMP-2在非小细胞肺癌中的表达及相关性研究%Correlation study of expression of IL-21 R and MMP-2 in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    戚胜波; 于奇

    2014-01-01

    目的:检测白介素-21受体(interleukin-21R,IL-21R)、基质金属蛋白酶-2(matrix metalloprotein-ases-2,MMP-2)在非小细胞肺癌( Non-small-cell lung cancer,NSCLC)癌组织中的表达,并探讨IL-21R、MMP-2的表达在NSCLC发生、发展及浸润转移的影响。方法采用免疫组化法检测50例NSCLC组织及20例正常肺组织对照组中IL-21R、MMP-2的表达,分析其阳性表达率与NSCLC患者临床病理特征的关系,并探讨其相关性。结果 NSCLC癌组织中IL-21R、MMP-2的阳性表达率均显著高于正常肺组织,且两者表达呈负相关(P<0.05);IL-21R和MMP-2的表达与淋巴结转移、临床分期及组织分化程度相关。结论 NSCLC中MMP-2的表达与其浸润转移正相关,其表达增加表示NSCLC有较高恶性生物学行为;IL-21R的表达与NSCLC浸润转移的呈负相关,且IL-21R、MMP-2在NSCLC发生及浸润过程中具有相关性。%Objective To investigate the expression of interleukin-21 receptor (IL-2R) and matrix metallo-proteinase-2 (MMP-2) in patients with non-small cell lung cancer (NSCLC), and to discuss the influence of the ex-pression of IL-21R and MMP-2 to the disease. Methods The expression of IL-21R and MMP-2 was detected by im-munohistochemical method in 50 patients with non-small cell lung cancer and 20 people with normal lung tissue. The correlation of the positive expression rate of IL-21R and MMP-2 to pathological characteristics was analyzed. Results The positive rate of IL-2R and MMP-2 in NSCLC patients was significantly higher than in the control group, and they were negatively correlated (P<0. 05). The expression of IL-21R and MMP-2 was related to clinical stages, lymph node metastasis status and tissue differentiation degree. Conclusion The expression of MMP-2 in NSCLC pa-tients is positively related with metastasis, which the increased expression shows higher malignant biological behavior in NSCLC patients. The expression of IL-21 R shows a negative correlation

  19. Expression of MMP-2 and TIMP-2 in malignant peripheral nerve sheath tumors%恶性外周神经鞘膜瘤中MMP-2和TIMP-2的表达

    Institute of Scientific and Technical Information of China (English)

    鲁华东; 吕长虹

    2005-01-01

    目的探讨恶性外周神经鞘膜瘤(malignant peripheral nerve sheath tumors,MPNST)中基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及其相应的组织金属蛋白酶抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)蛋白表达与病理分级、转移及预后的关系.方法采用免疫组化S-P法检测MPNST中MMP-2及TIMP-2表达,并行回顾性随访.结果 58例MPNST中MMP-2阳性表达51例,阳性表达率是87.9%,TIMP-2阳性表达36例,阳性表达率是62.1%. MMP-2蛋白表达与病理学分级、远处转移率呈正相关,与术后生存率呈负相关;而TIMP-2则相反.结论 MMP-2、TIMP-2与MPNST病理学分级、远处转移及术后生存期有关,可作为判断肿瘤恶性程度及预后的有用的参考指标.

  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. MMP-2、MMP-7蛋白在胃癌组织中表达的意义%The significance of MMP-2 and MMP-7 protein expression in human gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    潘留兰; 鲍晓蕾; 陈永胜; 王艳芬; 娄燕

    2007-01-01

    目的 探讨基质金属蛋白酶MMP-2、MMP-7在胃癌组织中的表达、侵袭及转移的关系.方法 应用免疫组化SP法检测87例胃癌组织、癌旁组织及正常胃组织中MMP-2、MMP-7的表达情况.结果 MMP-2、MMP-7在正常胃组织表达率为阴性,在癌旁组织中有低表达,分别为18.4%、21.8%,在胃癌组织中表达率明显增高,且表达率的高低与淋巴结转移、分化程度、浸润程度呈密切相关性(P<0.05).且MMP-2、MMP-7在胃癌组织中表达具有相关性.结论 MMP-2、MMP-7在胃癌组织中的高表达且两者呈正相关,并对胃癌的预后判定有一定意义.

  2. 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.

  3. CD147、MMP-2在人脑胶质瘤中的表达及其与预后的关系%Expression of CD147 and MMP-2 in Human Gliomas and Its Correlations with Prognosis

    Institute of Scientific and Technical Information of China (English)

    李浩; 陈兢; 贺民; 惠旭辉; 蔡博文; 李杨

    2007-01-01

    目的 探讨CD147和基质金属蛋白酶2(matrix metalloproteinases-2,MMP-2)在胶质瘤中的表达,及其与胶质瘤预后的关系.方法 采用免疫组化SP法检测50例胶质瘤标本中CD147和MMP-2蛋白的表达,采用RT-PCR对各级别胶质瘤中CD147的mRNA进行半定量分析,并结合随访资料进行分析.结果 胶质瘤标本中CD147蛋白阳性表达率为72.0%,MMP-2蛋白阳性表达率为78.0%,二者联合表达率70.0%,CD147蛋白的表达与MMP-2蛋白的表达之间存在正相关(r=0.737,P<0.01),RT-PCR检测到各级别胶质瘤标本中均有CD147 mRNA的表达;且随着胶质瘤级别增高,CD147和MMP-2蛋白的表达强度增高,CD147 mRNA表达水平也增高.预后分析证实CD147的表达越高,患者生存期越短.结论 CD147和MMP-2的表达与胶质瘤的恶性程度及预后关系密切,二者可作为胶质瘤患者判断临床预后和制定诊疗计划有意义的参考指标.

  4. 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.

  5. 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.

  6. Time-dependent Expression of MMP-2 and TIMP-2 after Rats Skeletal Muscle Contusion and Their Application to Determine Wound Age.

    Science.gov (United States)

    Yu, Tian-shui; Li, Zhuang; Zhao, Rui; Zhang, Yan; Zhang, Zhen-hua; Guan, Da-wei

    2016-03-01

    The ability to determine vitality and estimate the survival period after a wound is critical in routine forensic practice. The mRNA levels of MMP-2 and TIMP-2 were examined using quantitative real-time RT-PCR to determine the age of a wound. Furthermore, the colocalization of them with Macrophage Marker, respectively, was detected by double immunofluorescence, and a standardized rat model of skeletal muscle contusion was established. In the antemortem contused groups, a large number of macrophages showed positive staining for MMP-2 and TIMP-2, and the expression of MMP-2 and TIMP-2 mRNA increased sharply at 3 days postinjury, with relative quantities of 5.75 and 2.98. No samples in the other groups showed relative quantities of >5.75 and 2.98; therefore, relative quantities exceeding 5.75 and 2.98 were strongly indicated 3 days after contusion. In addition, there was a significant decrease in the relative quantity in the postmortem contused groups, indicating that they were useful for diagnosing vitality.

  7. MMP-2在去势牙周炎大鼠牙周组织中的表达%Expression of MMP-2 in periodondal tissue of ovariectomized rats with periodontitis

    Institute of Scientific and Technical Information of China (English)

    郭蕊欣; 马莉; 李金源

    2010-01-01

    目的 探讨雌激素水平降低与牙周炎之间的关系.方法 30只雌性Wister大鼠随机分为对照组、假手术组和去势组.利用丝线结扎牙齿的方法对去势组和假手术组大鼠构建牙周炎动物模型,免疫组化方法观察MMP-2在各组大鼠牙周组织中的不同表达.结果 去势组MMP-2呈强阳性表达,假手术组MMP-2的表达弱于去势组,对照组几乎不表达.同对照组比较,假手术组和去势组的平均光密度值均有统计学意义(P<0.05).去势组和假手术组平均光密度值的差异也有统计学意义(P<0.05).结论 MMP-2在雌激素低的大鼠牙周组织中的表达比雌激素正常的大鼠高,说明雌激素水平降低加重牙周组织的破坏.

  8. 儿童正畸牙移动龈沟液中MMP-2和TIMP-2的表达%Expressions of MMP-2 and TIMP-2 in gingival crevicular fluid of children during orthodontic tooth movement

    Institute of Scientific and Technical Information of China (English)

    苏哲君; 王鹏; 张艳波

    2013-01-01

    目的:探讨龈沟液中MMP-2和TIMP-2在正畸牙移动过程中可能发挥的作用.方法:选择24例拔除4颗第1双尖牙矫治青少年患者,牙列排齐整平后用弹性橡皮链150g正畸力拉尖牙向远中,上颌左侧尖牙为实验组加力150 g,右侧上颌尖牙为对照组不加力,分别在加力前、加力后1、4、7、t4、28天收集实验牙和对照牙远中临面处的龈沟液,用酶联免疫方法测定龈沟液中MMP-2和TIMP-2的含量.结果:实验组尖牙受力后龈沟液中MMP-2和TIMP-2在加力后1、4、7天时均增高,7天时达到高峰,后开始下降,28天恢复至加力前水平.对照组龈沟液中MMP-2和TIMP-2基本维持在基线水平.两组在加力后第4、7、14天MMP-2和TIMP-2的浓度差异有统计学意义(P<0.05).结论:正畸牙受力后龈沟液内MMP-2、TIMP-2表达水平发生动态规律性变化,MMP-2、TIMP-2参与了早期正畸牙移动牙周组织改建.

  9. Expression ind significance of MMP2 and type IV collagen in gastric cancer%基质金属蛋白酶及Ⅳ型胶原在胃癌中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    封国生; 谭毓铨

    2000-01-01

    目的探讨基质金属蛋白酶(MMP2)及Ⅳ型胶原与胃癌浸润转移的关系。方法对27例胃癌患者采用临床观察及免疫组化方法观察MMP2及Ⅳ型胶原在癌组织中的表达。结果MMP2在低分化腺癌、管状腺癌的癌细胞和癌间质中表达率分别为85.7%、77.7%,同时有Ⅳ型胶原的破坏;在血管淋巴管癌栓及淋巴结转移癌病例中表达率分别为83.3%、86.7%。结论 MMP2的高表达与胃癌浸润和转移有关,主要是破坏细胞外间质,尤其是Ⅳ型胶原。MMP2监测可做为判断患者预后的指标。%Objective To evaluate the relationship between the expression of MMP2, type IV callagen, and invasion and metastasis of gastric cancer. Mothods The expression of MMP2 and Type IV collagen was observed by using immunohistochemistry technique. Results The MMP2 expression clearly appeared in the poordifferentiated adenocarcinoma and tubular adenocarcinoma(85.7 %, 77.7 % ). Type IV collagen destruction was observed simultaneously. MMP2 was highly expressed in patients with cancer embolus in blood vessel and lymphatic vessel or with lymph node metastasis (83.3 %, 86.7 % ). Conclutions The high expression of MMP2 was significantly associated with infiltration and metastasis of gartric cancer. The extracellular matrix, especially type IV collagen was destructed in the cases of high expression of MMP2. These rusults suggest that monitoring the level of MMP2 expression may be an index for evaluation of prognosis.

  10. MMP-2和PTEN蛋白在膀胱癌组织中的表达及临床意义%Expressions of MMP-2 and PTEN proteins in bladder transitional cell carcinoma and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    邱道显; 王有昌; 王洪海; 郭来成; 郝丽娟

    2007-01-01

    目的:探讨基质金属蛋白酶-2(matrix metaloproteinase-2,MMp-2)和PTEN蛋白在膀胱癌组织中的表达及临床意义.方法:应用免疫组织化学PV-6000通用型二步法检测65例膀胱癌及10例正常膀胱组织中MMP-2和PTEN蛋白的表达.结果:MMP-2在正常膀胱组织中不表达,在65例膀胱癌组织中的阳性表达率为56.9%;随着肿瘤细胞病理分级、临床分期的增加,MMP-2阳性表达率逐渐增高,各组间比较差异有统计学意义,P<0.05.PTEN蛋白在正常膀胱组织中均呈阳性表达,在65例膀胱癌组织中的阳性表达率为46.2%;随着癌细胞病理分级、临床分期的增加,PTEN蛋白阳性表达率逐渐减低,各组间比较差异有统计学意义,P<0.05.结论:MMP-2和PTEN蛋白异常表达与膀胱癌的发生发展关系密切,检测两者在膀胱癌组织中的表达,可作为判断膀胱癌发生发展的有用指标.

  11. 哈萨克族食管癌中MMP-1、MMP-2、MMP-7、TIMP-1和MTA1的表达及其临床病理意义%The expression and significance of MMP.1, MMP.2, MMP.7,TIMP-1 and MTA1 in esophageal cancer of Kazaks

    Institute of Scientific and Technical Information of China (English)

    李秀梅; 陈艳; 王洪江; 庞作良; 李卉; 姜孝芳; 古丽努尔·木哈依; 谌宏鸣; 李惠武

    2011-01-01

    目的:探讨在新疆哈萨克族食管癌组织中基质金属蛋白酶1、2、7 (MMP-1、MMP-2、MMP-7)、基质金属蛋白酶抑制因子1(TIMP-1)和肿瘤转移相关基因1(MTA1)mRNA的表达及其临床意义.方法:采用RT-PCR方法检测75例哈萨克族食管癌标本中MMP-1、MMP-2、MMP-7、TIMP-1和MTA1 mRNA的表达水平,分析其表达与临床病理特征的关系.结果:MMP-1、MMP-2、MMP-7、TIMP-1和MTA1 mRNA在哈萨克族食管癌组织中的表达较正常组织增高,差异均具有统计学意义(P均<0.05);且MMP-2、MMP-7、MTA1 mRNA的表达与淋巴结转移有关(P<0.05),MMP-1、MMP-7 mRNA的表达与临床分期有关(P<0.05);TIMP-1与MMP-1、MMP-7、MTA1的表达呈正相关(r=0.446、0.458、0.333,P均<0.01).结论:MMP-1、MMP-2、MMP-7、TIMP-1和MTA1 mRNA表达上调共同参与了哈萨克族食管癌的发生发展过程;MMP-2、MMP-7和MTA1可能是哈萨克族食管癌发生侵袭、转移的主导因素.%OBJECTIVE:To study expressions of matrix metalloproteinasel, 2, 7 ( MMP-1, MMP-2, MMP-7), tissue inhibitor of matrix metallo proteinase 1(TIMP-1) and metastasis associated gene 1 (MTA1)in esophageal cancer tissue and normal tissue among Kazaks and to investigate the relationship between their expressions and clinical pathological features. METHODS: Using RT-PCR to detect the expressions of MMP-1, MMP-2, MMP-7, TIMP-1 and MTA1 in 75 esophageal cancer specimens. RESULTS: The mRNA expressions of MMP-1, MMP-2, MMP-7 , TIMP-1 and MTA1 in cancer tissue were higher than those of normal tissues(P<0.05). While the expression levels of MMP-2, MMP-7 and MTA1 mRNA were significantly related to the lymph node metastasis. The expression levels of MMP-1, MMP-7 mRNA were significantly related to the TNM stages(P < 0.05). The expression of TIMP-1 in the Kazak's esophageal cancer was positively related to the expressions of MMP-1, MMP-7, MTA1 (r=0.446、 0.458、 0.333, respectively, P<0.01). CONCLUSION: The overexpressions of MMP

  12. Effect of antisense TIMP-1 cDNA on the expression of TIMP-1 and MMP-2 in lung tissue with pulmonary fibrosis induced by bleomycin.

    Science.gov (United States)

    Tang, Haiying; Mao, Jingwei; Gao, Lili; Liu, Jia; Wu, Taihua

    2013-01-01

    The aim of this study was to observe the effect of antisense tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) cDNA on the concentration of hydroxyproline (HYP) and the expression of TIMP-1 and matrix metalloproteinase-2 (MMP-2) in the lung tissue of rats with bleomycin (BLM)‑induced pulmonary fibrosis. Sprague-Dawley rats were randomly divided into 5 groups: the control, pulmonary fibrosis model, sense TIMP-1 transfection, antisense TIMP-1 transfection and empty vector transfection groups. For the transfection groups, following the intratracheal injection of BLM on days 1, 3, 7, 14, 28 and 60, the rats were treated with retroviral vectors and sacrificed on day 28. The control and pulmonary fibrosis groups were treated with normal saline at the same time‑points. The concentration of HYP and the expression levels of TIMP-1 and MMP-2 in the lung tissue were detected. The HYP concentration and lung tissue TIMP-1 expression levels of the antisense TIMP-1 group decreased significantly on days 1 and 3 compared with those of the empty vector and pulmonary fibrosis groups at the same time-points (Ppulmonary fibrosis groups on days 7, 14, 28 and 60. The lung expression levels of MMP-2 in all groups, with the exception of the control group, had no significant differences at all time-points (P>0.05). Antisense TIMP-1 cDNA retroviral vectors are able to suppress the development of pulmonary fibrosis in the early stages.

  13. MMP-2 Alters VEGF Expression via αVβ3 Integrin-Mediated PI3K/AKT Signaling in A549 Lung Cancer Cells

    OpenAIRE

    2010-01-01

    Vascular endothelial growth factor (VEGF) is one of the most important angiogenic growth factors for tumor angiogenesis. Here, we sought to explore whether RNA interference (RNAi) targeting Matrix metalloproteinase-2 (MMP-2) could disrupt VEGF mediated angiogenesis in lung cancer. MMP-2 siRNA inhibited lung cancer cell-induced tube formation of endothelial cells in vitro; addition of recombinant human-MMP-2 restored angiogenesis. MMP-2 transcriptional suppression decreased VEGF, PI3K protein ...

  14. p38α MAPK mediates 17β-estradiol inhibition of MMP-2 and -9 expression and cell migration in human lovo colon cancer cells.

    Science.gov (United States)

    Hsu, Hsi-Hsien; Liu, Chung-Jung; Shen, Chia-Yao; Chen, Yi-Jyun; Chen, Li-Mien; Kuo, Wu-Hsien; Lin, Yueh-Min; Chen, Ray-Jade; Tsai, Chang-Hai; Tsai, Fuu-Jen; Huang, Chih-Yang

    2012-11-01

    Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17β-estradiol (E(2)) treatment is sufficient to inhibit cell proliferation and cell migration in human colon cancer cells. Up-regulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and matrix metallopeptidases (MMPs) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. In the present study, we treated human LoVo colon cancer cells with E(2) to explore whether E(2) down-regulates cell proliferation and migration, and to identify the precise molecular and cellular mechanisms behind the down-regulatory responses. Here, we found that E(2) treatment decreased cell proliferation and cell cycle-regulating factors such as cyclin A, cyclin D1 and cyclin E. At the same time, E(2) significantly inhibited cell migration and migration-related factors such as uPA, tPA, MMP-2, and MMP-9. However, E(2) treatment showed no effects on upregulating expression of plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1, -2, -3, and -4 (TIMP-1, -2, -3, and -4). After administration of inhibitors including QNZ (NFκB inhibitor), LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor) or SP600125 (JNK1/2 inhibitor), E(2) -downregulated cell migration and expression of MMP-2 and MMP-9 in LoVo cells is markedly inhibited only by p38 MAPK inhibitors, SB203580. Application of specific target gene siRNA (ERα, ERβ, p38α, and p38β) to LoVo cells further confirmed that p38 MAPK mediates E(2) /ERs inhibition of MMP-2 and -9 expression and cell motility in LoVo cells. Collectively, these results suggest that E(2) treatment down-regulates cell proliferation by modulating the expression of cyclin A, cyclin D1 and cyclin E. E(2) treatment simultaneously impaired cell migration by

  15. Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for proMMP-2 generates active MMP-2.

    Science.gov (United States)

    Nishida, Yuki; Miyamori, Hisashi; Thompson, Erik W; Takino, Takahisa; Endo, Yoshio; Sato, Hiroshi

    2008-11-01

    The suggested model for pro-matrix metalloproteinase-2 (proMMP-2) activation by membrane type 1 MMP (MT1-MMP) implicates the complex between MT1-MMP and tissue inhibitor of MMP-2 (TIMP-2) as a receptor for proMMP-2. To dissect this model and assess the pathologic significance of MMP-2 activation, an artificial receptor for proMMP-2 was created by replacing the signal sequence of TIMP-2 with cytoplasmic/transmembrane domain of type II transmembrane mosaic serine protease (MSP-T2). Unlike TIMP-2, MSP-T2 served as a receptor for proMMP-2 without inhibiting MT1-MMP, and generated TIMP-2-free active MMP-2 even at a low level of MT1-MMP. Thus, MSP-T2 did not affect direct cleavage of the substrate testican-1 by MT1-MMP, whereas TIMP-2 inhibited it even at the level that stimulates proMMP-2 processing. Expression of MSP-T2 in HT1080 cells enhanced MMP-2 activation by endogenous MT1-MMP and caused intensive hydrolysis of collagen gel. Expression of MSP-T2 in U87 glioma cells, which express a trace level of endogenous MT1-MMP, induced MMP-2 activation and enhanced cell-associated protease activity, activation of extracellular signal-regulated kinase, and metastatic ability into chick embryonic liver and lung. MT1-MMP can exert both maximum MMP-2 activation and direct cleavage of substrates with MSP-T2, which cannot be achieved with TIMP-2. These results suggest that MMP-2 activation by MT1-MMP potentially amplifies protease activity, and combination with direct cleavage of substrate causes effective tissue degradation and enhances tumor invasion and metastasis, which highlights the complex role of TIMP-2. MSP-T2 is a unique tool to analyze physiologic and pathologic roles of MMP-2 and MT1-MMP in comparison with TIMP-2.

  16. Osthole ameliorates acute myocardial infarction in rats by decreasing the expression of inflammatory-related cytokines, diminishing MMP-2 expression and activating p-ERK.

    Science.gov (United States)

    Duan, Juan; Yang, Yu; Liu, Hong; Dou, Peng-Cheng; Tan, Sheng-Yu

    2016-01-01

    Osthole, the active constituent of Cnidium monnieri extracts, has been shown to have a diverse range of pharmacological properties. In the present study, we aimed to evaluate the cardioprotective effects of osthole in a rat model of acute myocardial infarction (AMI). The rats with AMI were treated with 1, 3 and 10 mg/kg of osthole or the vehicle for 4 weeks. The infarct size of the rats with AMI was measured, and casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) activities in the rats with AMI were analyzed using commercially available kits. The nuclear factor-κB (NF-κB), tumor necrosis factor‑α (TNF-α), interleukin (IL)-1β and IL-6 levels in whole blood from rats with AMI were also detected using commercially available kits. The levels of Toll-like receptors 2/4 (TLR2/4) and nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) were also detected by RT-qPCR. Moreover, the protein expression levels of endothelial nitric oxide synthase (eNOS) and mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, cyclooxygenase-2 (COX-2), as well as matrix metalloproteinase-2 (MMP-2) were all assayed by western blot analysis. Our results revealed that osthole markedly reduced the infarct size, and the levels of CK, CK-MB, LDH and cTnT in the rats with AMI, and that these cardioprotective effects may be associated with the inhibition of inflammatory reactions, the reduction in MMP-2 activity and the activation of MAPK cascades.

  17. The relationship between oral squamous cell carcinoma of MMP-1, MMP-2, UPA's expression of tumor invasion and metastasis%口腔鳞癌中MMP-1、MMP-2、uPA的表达与肿瘤侵袭和转移的关系

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

      目的探讨基质金属蛋白酶-1、2(MMP-1、MMP-2)及尿激酶型纤溶酶原激活物(uPA)的表达与口腔鳞癌侵袭和转移的关系。方法选取我院收治的60例口腔鳞癌患者,用免疫组化检测癌旁正常组织和癌组织中MMP-1、MM P-2、uPA的含量并进行比较。结果口腔鳞癌患者肿瘤组织与口腔癌旁正常组织MMP-1、MMP-2、uPA的含量有统计学差异(P <0.05)。结论口腔鳞癌中MMP-1、MMP-2、uPA的表达与肿瘤的侵袭、转移有着密切的关系,有可能成为评价肿瘤侵袭、转移程度的指标。%Objective To investigate the relationship between MMP-1, MMP-2, UPA's expression in oral squamous cell carcinoma invasion and metastasis, to provide experimental evidence for tumor treatment and prognosis. Methods 60 patients with oral squamous cell carcinoma patients in our hospitalwere for the study, immunohistochemical detection of adjacent normal tissue and cancer tissue in MMP-1, the MM P -2, UPA's content. Results Patients with oral squamous cell carcinoma tumor cavity adjacent normal tissue MMP-1, MMP-2, the UPA's content difference were significant(P <0.05). Conclusion Oral squamous cell carcinoma of MMP-1, MMP-2, UPA's expression in tumor invasion and metastasis are closely related, it is possible to become the evaluation of invasion, metastasis indicators.

  18. Low-dose decitabine induces MAGE-A expression and inhibits invasion via suppression of NF-κB2 and MMP2 in Eca109 cells.

    Science.gov (United States)

    Liu, Wei-hua; Sang, Mei-xiang; Hou, Shu-yun; Zhang, Chao; Shan, Bao-en

    2014-07-01

    Decitabine, a demethylating drug, is the first-line treatment for myelodysplastic syndromes and gains better overall survival, which is based on epigenetic mechanism. Activated by promoter demethylation, melanoma-associated antigens-A (MAGE-A), cancer-testis antigens are attractive targets for immunotherapy. Our purpose was to investigate whether decitabine could show anti-tumor effects for esophageal cancer and explore its mechanism. In addition, we aimed to examine its modulation for most MAGE-A members. The results showed the baseline expression were MAGE-A2, -3,-9, and -10 in Eca109 cells and decitabine (0.5 μM) could induce MAGE-A8 and -A4 whereas reduce MAGE-A9 and -A10. Moreover, decitabine (0.5 μM) inhibited cell proliferation, migration and invasive ability by 15%, 34% and 47.2%, respectively and decreased expressions of NF-κB2 and MMP2. Our results demonstrated that low-dose decitabine induced the expression of MAGE-A8 and -A4, and inhibited cell invasion through decreasing expression of MMP2 and NF-κB2, which provides possibilities for combing decitabine with immunotherapy targeting MAGE-A to treat advanced esophageal squamous cell carcinoma.

  19. 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.

  20. DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway.

    Science.gov (United States)

    Poudel, Barun; Lee, Young-Mi; Kim, Dae-Ki

    2015-04-01

    Metastatic melanoma is one of the most deadly and evasive cancers. Collagen I in the extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP) 2 and 9. Discoidin domain receptor (DDR) 2 is a collagen receptor that is implicated in several cancer types including breast and prostate cancers. However, the role of DDR2 in the migration and invasion of murine melanoma cells is less studied. In the present study, we investigated the effects and underlying mechanisms of DDR2 in migration and invasion of B16BL6 melanoma cells in response to collagen I. Results demonstrated that DDR2 is expressed and is phosphorylated by collagen I in the cells. Upon down-regulation of DDR2 using small-interfering RNA (siRNA) approach, both of the cell migratory and invasive phenotypes were significantly attenuated when compared with the control cells. This effect was mediated via suppression of MMP2/9 upon DDR2 inhibition. Furthermore, inhibition of DDR2 by specific siRNA markedly reduced the activation of extracellular regulated kinase (ERK) 1 and 2 and nuclear factor of kappa B (NF-κB) in the cells when compared with the control cells. Overall, these data demonstrated that DDR2 siRNA-mediated suppression of ERK1/2 and NF-κB could down-regulate the expressions of MMP2/9 in response to collagen I to reduce the migratory and invasive phenotypes of the cells.

  1. Expression and effect of matrix metalloproteinase 2 in human fetal scleral fibroblasts treated with an extremely low frequency electromagnetic field%极低频电磁辐射下HFSF中MMP-2的表达及作用

    Institute of Scientific and Technical Information of China (English)

    田甜; 朱煌

    2015-01-01

    Objective To observe the matrix metalloproteinase 2 (MMP-2) activity and protein expression in human fetal scleral fibroblasts (HFSFs) exposed to an extremely low frequency electromagnetic field (ELF-EMF) and its impact on collagen Ⅰ synthesis.Methods This was an experimental study.HFSFs were cultured and divided into a control group,radiation group and inhibitor group according to their exposure to 50 Hz,0.2 mT electromagnetic field or joint MMP-2 specific inhibitors (sc-204092).MMP-2 activity was measured by gelatin enzymography.MMP-2 and collagen Ⅰ protein expression were detected by Western Blot.A single factor analysis of variance was used to determine whether there was a difference among these groups.Results There were significant differences between the three groups (F=14.96,139.88,63.46,P<0.01).Compared to the control group,MMP-2 activity and protein expression increased in the radiation group (P<0.05) and collagen Ⅰ protein expression decreased (P<0.01).Compared to the radiation group,MMP-2 activity and protein expression decreased in the inhibitor group (P<0.01) and collagen Ⅰ protein expression increased (P<0.05).Conclusion ELF-EMF may regulate the synthesis of collagen Ⅰ by affecting the activity and protein expression of MMP-2.%目的 研究极低频电磁场(ELF-EMF)作用下人胚胎眼巩膜成纤维细胞(HFSF)中基质金属蛋白酶-2(MMP-2)活性与蛋白表达的变化以及ELF-EMF对Ⅰ型胶原(Collagen Ⅰ)合成的影响.方法 实验研究.根据是否暴露于50 Hz、0.2 mT电磁场或加入MMP-2特异性抑制剂(sc-204092),将实验细胞分为对照组、辐照组和抑制剂组.明胶酶谱法检测各组HFSF中MMP-2酶活性的变化;Western Blot法检测各组HFSF中MMP-2、Collagen Ⅰ蛋白水平的变化.采用单因素方差分析进行数据分析.结果 3组HFSF细胞中MMP-2酶活性、MMP-2、Collagen Ⅰ蛋白表达比较差异均具有统计学意义(F=14.96、139.88、63.46,P均<0.01);辐照组较对照组MMP

  2. The expression and clinical significance of MMP-2 and MMP-7 in colorectal carcinomas%基质金属蛋白酶-2、7在结直肠癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    郭德智; 张宝良; 郑永强; 李晓军

    2009-01-01

    Objective To investigate the expression of MMP-2 and MMP-7 and their elinieopathologieal significance in eoloreetal carcinomas. Methods The expression of MMP-2 mRNA, MMP-7 mRNA and MMP-2, MMP-7 in 42 samples of eoloreetal carcinomas and its adjacent normal eoloreetal mueosa were examined using fluo-rescence quantitative RT-PCR (FQ-RT-PCR) and immunohistoehemistry. The relationship of their expression with some elinieopathologieal characteristics was analyzed. Results MMP-2 mRNA, MMP-7 mRNA and MMP-2, MMP-7 were significantly over-expressed in eoloreetal carcinomas compared with its adjacent normal eoloreetal mueosa( P < 0.05 ) , and they were positively associated with bowel wall invasion, the regional lymph node metastasis and Dukes stage. The expression of MMP-2 mRNA and MMP-7 mRNA was positively correlated with MMP-2 and MMP-7 in eoloreetal eareinornas. Conclusions MMP-2 and MMP-7 may play a key role in eoloreetal carcinogenesis,tumor in-vasion and metastasis. Examination of combined MMP-2 and MMP-7 expression may have an important significance to judge the malignant degree and biological behavior of human eoloreetal carcinoma and for evaluating the progno-sis.%目的 探讨结直肠癌中基质金属蛋白酶-2、7(MMP-2、MMP-7)的表达及其临床意义.方法 采用荧光定量逆转录PCR(FQ-RT-PCR)法和免疫组化法检测42例结直肠癌组织及其邻近正常黏膜组织中MMP-2 mRNA和MMP-7 mRNA及其蛋白,并分析其与结直肠癌临床病理特征的关系.结果 结直肠癌组织MMP-2 mRNA、MMP-7 mRNA的转录水平和MMP-2、MMP-7的表达水平均显著高于邻近正常黏膜组织(P均<0.05),且均与浸润深度、淋巴结转移、Dukes分期正相关.结直肠癌组织MMP-2 mRNA转录水平和MMP-7 mRNA转录水平、MMP-2表达水平和MMP-7表达水平均呈正相关(rs=0.454,P=0.003;rs=0.343,P=0.026).结论 MMP-2和MMP-7在结直肠癌发生发展中起重要作用,联合检测二者有助于结直肠癌的恶性程度及生物

  3. Effect of Lutein and Antioxidant Supplementation on VEGF Expression, MMP-2 Activity, and Ultrastructural Alterations in Apolipoprotein E-Deficient Mouse

    Directory of Open Access Journals (Sweden)

    Patricia Fernández-Robredo

    2013-01-01

    Full Text Available Oxidative stress is involved in the pathogenesis of several diseases such as atherosclerosis and age-related macular degeneration (AMD. ApoE-deficient mice (apoE−/− are a well-established model of genetic hypercholesterolemia and develop retinal alterations similar to those found in humans with AMD. Thus supplementation with lutein or multivitamin plus lutein and glutathione complex (MV could prevent the onset of these alterations. ApoE−/− mice (n=40, 3 months old were treated daily for 3 months with lutein (AE-LUT or MV (two doses: AE-MV15 (15 mg/kg/day and AE-MV50 (50 mg/kg/day and were compared to controls with vehicle (AE-C. Wild-type mice (n=10 were also used as control (WT-C. ApoE−/− mice showed higher retinal lipid peroxidation and increased VEGF expression and MMP-2 activity, associated with ultrastructural alterations such as basal laminar deposits, vacuoles, and an increase in Bruch's membrane thickness. While lutein alone partially prevented the alterations observed in apoE−/− mice, MV treatment substantially reduced VEGF levels and MMP-2 activity and ameliorated the retinal morphological alterations. These results suggest that oxidative stress in addition to an increased expression and activity of proangiogenic factors could participate in the onset or development of retinal alterations of apoE−/− mice. Moreover, these changes could be prevented by efficient antioxidant treatments.

  4. 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

  5. A novel cell line derived from pleomorphic adenoma expresses MMP2, MMP9, TIMP1, TIMP2, and shows numeric chromosomal anomalies.

    Directory of Open Access Journals (Sweden)

    Aline Semblano Carreira Falcão

    Full Text Available Pleomorphic adenoma is the most common salivary gland neoplasm, and it can be locally invasive, despite its slow growth. This study aimed to establish a novel cell line (AP-1 derived from a human pleomorphic adenoma sample to better understand local invasiveness of this tumor. AP-1 cell line was characterized by cell growth analysis, expression of epithelial and myoepithelial markers by immunofluorescence, electron microscopy, 3D cell culture assays, cytogenetic features and transcriptomic study. Expression of matrix metalloproteinases (MMPs and their tissue inhibitors (TIMPs was also analyzed by immunofluorescence and zymography. Furthermore, epithelial and myoepithelial markers, MMPs and TIMPs were studied in the tumor that originated the cell line. AP-1 cells showed neoplastic epithelial and myoepithelial markers, such as cytokeratins, vimentin, S100 protein and smooth-muscle actin. These molecules were also found in vivo, in the tumor that originated the cell line. MMPs and TIMPs were observed in vivo and in AP-1 cells. Growth curve showed that AP-1 exhibited a doubling time of 3.342 days. AP-1 cells grown inside Matrigel recapitulated tumor architecture. Different numerical and structural chromosomal anomalies were visualized in cytogenetic analysis. Transcriptomic analysis addressed expression of 7 target genes (VIM, TIMP2, MMP2, MMP9, TIMP1, ACTA2 e PLAG1. Results were compared to transcriptomic profile of non-neoplastic salivary gland cells (HSG. Only MMP9 was not expressed in both libraries, and VIM was expressed solely in AP-1 library. The major difference regarding gene expression level between AP-1 and HSG samples occurred for MMP2. This gene was 184 times more expressed in AP-1 cells. Our findings suggest that AP-1 cell line could be a useful model for further studies on pleomorphic adenoma biology.

  6. A novel cell line derived from pleomorphic adenoma expresses MMP2, MMP9, TIMP1, TIMP2, and shows numeric chromosomal anomalies.

    Science.gov (United States)

    Falcão, Aline Semblano Carreira; Kataoka, Maria Sueli da Silva; Ribeiro, Nélson Antonio Bailão; Diniz, José Antonio Picanço; Alves, Sérgio Melo; Ribeiro, André L Ribeiro; de Siqueira, Adriane Sousa; da Silva, Artur Luiz; Ramos, Rommel Thiago Jucá; Freitas, Vanessa M; Jaeger, Ruy G; Pinheiro, João J V

    2014-01-01

    Pleomorphic adenoma is the most common salivary gland neoplasm, and it can be locally invasive, despite its slow growth. This study aimed to establish a novel cell line (AP-1) derived from a human pleomorphic adenoma sample to better understand local invasiveness of this tumor. AP-1 cell line was characterized by cell growth analysis, expression of epithelial and myoepithelial markers by immunofluorescence, electron microscopy, 3D cell culture assays, cytogenetic features and transcriptomic study. Expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) was also analyzed by immunofluorescence and zymography. Furthermore, epithelial and myoepithelial markers, MMPs and TIMPs were studied in the tumor that originated the cell line. AP-1 cells showed neoplastic epithelial and myoepithelial markers, such as cytokeratins, vimentin, S100 protein and smooth-muscle actin. These molecules were also found in vivo, in the tumor that originated the cell line. MMPs and TIMPs were observed in vivo and in AP-1 cells. Growth curve showed that AP-1 exhibited a doubling time of 3.342 days. AP-1 cells grown inside Matrigel recapitulated tumor architecture. Different numerical and structural chromosomal anomalies were visualized in cytogenetic analysis. Transcriptomic analysis addressed expression of 7 target genes (VIM, TIMP2, MMP2, MMP9, TIMP1, ACTA2 e PLAG1). Results were compared to transcriptomic profile of non-neoplastic salivary gland cells (HSG). Only MMP9 was not expressed in both libraries, and VIM was expressed solely in AP-1 library. The major difference regarding gene expression level between AP-1 and HSG samples occurred for MMP2. This gene was 184 times more expressed in AP-1 cells. Our findings suggest that AP-1 cell line could be a useful model for further studies on pleomorphic adenoma biology.

  7. The Expression of MMP-2 Following Immobilization and High-Intensity Running in Plantaris Muscle Fiber in Rats

    Directory of Open Access Journals (Sweden)

    Eli Carmeli

    2006-01-01

    Full Text Available The effect of 2-week, high-intensity running and a 2-week immobilization on muscle fiber type composition of the plantaris muscle from 18 female, 6-month-old Wistar rats (running, n = 6; immobilization, n = 6; sedentary control, n = 6 was bio- and histochemically investigated. The high-intensity treadmill running began with 20 min (32 m/min, 0% gradient, 75% VO2 max, up to 50 min/day. Right hind limbs were immobilized by an external fixation procedure for 13 days. Muscle mass of the plantaris muscle in the immobilized groups was reduced by 16% in comparison with the sedentary control group. High-intensity running and immobilization increased both mRNA and protein levels of matrix metalloproteinase type 2 (MMP-2 in plantaris. Running and immobilization decreased the percentages of transverse sectional area of fast-twitch glycolytic (FG type IIb fibers, running increased relative cross-sectional area of fast-twitch oxidative glycolytic (FOG type IIa muscle fibers, whereas immobilization increased relative cross-sectional area of slow-twitch oxidative (SO muscle fibers (type I. Our results suggest that both high-intensity running and immobilization are enough to induce overwhelming changes in plantaris.

  8. Taiwanin E inhibits cell migration in human LoVo colon cancer cells by suppressing MMP-2/9 expression via p38 MAPK pathway.

    Science.gov (United States)

    Hsu, Hsi-Hsien; Kuo, Wei-Wen; Day, Cecilia Hsuan; Shibu, Marthandam Asokan; Li, Shin-Yi; Chang, Sheng-Huang; Shih, Hui-Nung; Chen, Ray-Jade; Viswanadha, Vijaya Padma; Kuo, Yueh-Hsiung; Huang, Chih-Yang

    2016-11-03

    Taiwanin E is a natural compound which is structurally analogous to estrogen II and is abundantly found in Taiwania cryptomerioides. It has been previously reported for its anticancer effects; however, the pharmaceutical effect of Taiwanin E on Human LoVo colon cancer cells is not clear. In this study, we investigated the effects of Taiwanin E on metastasis and the associated mechanism of action on Human LoVo colon cancer cells with respect to the modulations in their cell migration and signaling pathways associated with migration. The results showed that Taiwanin E inhibited cell migration ability correlated with reduced expression and activity of MMP-2 and MMP-9. In addition, Taiwanin E induced activation of p38 through phosphorylation. Inhibition of p38α/β significantly abolished the effect of Taiwanin E on cell migration and MMP-2/-9 activity. Our results conclude that Taiwanin E inhibited cell migration chiefly via p38α MAPK pathway and in a lesser extend via p38β MAPK. The results elucidate the potential of the phytoestrogen natural compound Taiwanin E as a cancer therapeutic agent in inhibiting the cell migration. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.

  9. 胃癌中SDF-1、CXCR4、MMP-2和MMP-9的表达及意义%Expression of SDF-1,CXCR4,MMP-2 and MMP-9 in tissues of gastric carcinoma and their significances

    Institute of Scientific and Technical Information of China (English)

    陈友权; 于燕妮

    2012-01-01

    Purpose To study the expression of stromal cell derived factor l( SDF-1 ), CXCR4, MMP-2 and MMP-9 and their association with clinic pathological features and lymph node metastasis in gastric carcinoma. Methods The expression of SDF-1, CXCR4, MMP-2 and MMP-9 was detected by immunohistochemistry in 109 cases of the gastric carcinoma. The correlation with various clinico-pathologic parameters was analyzed. Results The positive rates of SDF-1, CXCR4, MMP-2 and MMP-9 were 87. 9% , 56. 9% , 77. 6% and 81. 0% in gastric carcinoma, respectively, which were much higher than those 47. 8% , 30. 4% , 47. 8% and 43. 4% in cutting edge of the control group. There existed significant different between two groups( P <0. 05 ). SDF-1 and CXCR4 expression in lymph node-metastasis group was higher than that without lymph node metastasis( P <0. 05 ). The expression of SDF-1 and CXCR4 was correlated positively to lymph node metastasis,clinic tumor stage,histologic grade,and serosal invasion( P <0. 05 ). The expression of CXCR4 and MMP-2 was positively correlated to lymph node metastasis, serosal invasion and clinical stage( P <0. 05 ). The expression of SDF-1 was significantly correlated with CXCR4、MMP-2 and MMP-9( P <0. 05 ). Conclusions The expression of SDF-1, CXCR4, MMP-2 and MMP-9 of tumor is involved in tumorgenesis and associated with invasion and lymphnode metastasis of gastric carcinoma, which can serve as biomarkers for diagnosis and prediction of lymph node metastasis. Furthermore, the expression of SDF-1 in gastric carcinoma may promote the tumor invasion and metastasis through the secretion of MMP-2 and MMP-9, suggesting that SDF-1 may be an important target for targeted therapy.%目的 研究趋化因子SDF-1及其受体CXCR4以及MMP-2和MMP-9在胃癌中的表达,探讨SDF-1对MMP-2和MMP-9表达的影响.方法 应用免疫组化EnVision两步法检测109例胃癌组织中SDF-1、CXCR4、MMP-2和MMP-9的表达.结果 (1)SDF-1、CXCR4、MMP-2、MMP-9在胃癌组

  10. EXPRESSION AND SIGNIFICANCE OF THE NOVEL HYPERPLASIC SUPPRESS GENE IN THE PROCESS OF BREAST CANCER%HSG、MMP-2和MMP-9在乳腺癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    夏庆安; 付玉环; 姜广建

    2012-01-01

    [目的]探讨新的增殖抑制基因(hyperplasic suppressor gene,HSG)和基质金属蛋白酶-2、9(matrix metalloproteinase-2,-9 MMP-2,9)在乳腺癌组织中的表达及意义.[方法]应用免疫组化方法检测唐山市工人医院52例乳腺癌标本和18例乳腺纤维腺瘤标本中HSG、MMP-2和MMP-9表达.[结果]52例乳腺癌组织中HSG、MMP-2和MMP-9的表达分别为46.2% (24/52)、73.1% (38/52)和63.5% (33/52),在乳腺纤维腺瘤中,MMP-2和MMP-9着色很少,HSG的着色很深,表明三者与肿瘤的发生有关;MMP-2的表达与肿瘤的TNM分期、淋巴结转移和预后复发有关(P<005);乳腺癌组HSG低表达和MMP-9高表达,与淋巴结转移有关(P<005),且HSG和MMP-2、MMP-9呈负相关(r=-0.27,P< 0.05).[结论]乳腺癌组织中MMP-2高表达预示着病人预后更差,比MMP-9对乳腺癌与后的判断更有价值.综合检测HSG、MMP-2和MMP-9的表达更有利于了解乳腺癌转移的作用机制,更好地判断乳腺癌的进展及预后.%[Objective] To determine the expression and significance of the novel hyperplasic suppress gene (HSG) and matrix metaUoproteinase-2, -9 (MMP-2, -9) in the process of breast cancer. [Methods] Iramunohistochemistry method was used to measure the expression of HSG and raetalIoproteinase-2, -9, in which 52 cases were breast cancer samples, 18 cases were breast Cbroadenoma samples. All these cases were collected by the Department of pathology of the Tangshan Worker/s Hospital. [Resufts] The positive rate of HSG, MMP-2, -9 was 46.2% (24/52), 73.1% (38/52) and 65.3% (33/52) in breast cancer tissues, respectively- A very weak Btaining of MMP-2, -9 was observed in only a few epidielia in surrounding background breast tissue and flbrooadenoma tissue, but observed a very strong staining of HSG. The presence of HSG, MMP-2, -9 was significantly greater in breast cancer tissues compared with all other breast tissues; The high leve of MMP-2 was associated with the tumor grade, lymph

  11. Effects of salidroside on the expression of MMP-2 and TIMP-1 in paraquat poisoning pulmonary fibrosis rats%红景天苷对百草枯中毒大鼠肺组织MMP-2及TIMP-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨洞洞; 张卓一; 李杏; 徐俪颖

    2014-01-01

    Objective To explore the effect of salidroside(SDS) on the expression of matrix metalloproteinase-2(MMP-2) and the tissue inhibitor of metalloproteinase-1(TIMP-1) in paraquat poisoning pulmonary fibrosis rats. Methods Ninety Sprague-Dawley rats (sanitary degree) were randomly divided into normal group (n=10), model group (n=40) and SDS treatment group(n=40). The model group and SDS treatment group were randomly divided into four subgroups with 10 cas-es each according to different time points of sacrifice. And then the model group and SDS treatment group made the lung injury model induced by PQ poisoning at 1 hour, 6 hours, 24 hours and 72 hours respectively. After the poisoning, SDS group was given SDS, 10mg/kg, per 12 hours while the model group was given normal saline solution with the same vol-ume until sacrifice. The immunohistochemistry was used to determine the expressions of MMP-2 protein and TIMP protein. The levels of MMP-2 mRNA and TIMP mRNA were examined by real-time PCR. Results The expression of MMP-2, TIMP-1 and MMP-2mRNA in PQ model group and SDS treatment group were gradually increased with the time prolonged (t=23.50, 34.89, 59.96, 11.40, 30.46, 19.07; 7.50, 20.24, 24.23, 12.75, 16.73, 3.99; 4.98, 10.16, 16.12, 5.17, 11.14, 5.96;21.73, 50.04, 58.86, 28.31, 37.13, 8.82; 6.05,18.04, 19.72, 11.99, 13.68;3.68, 7.83, 13.04, 4.15, 9.36, 5.21, P<0.05). Compared to control group, the expression of MMP-2,TIMP-1, MMP-2 mRNA and TIMP-1 mRNA in PQ model group and SDS treatment group at 6 hours,24 hours and 72 hours were significantly increased (t=37.65, 67.01, 55.06; 24.94, 53.76, 42.60; 9.11, 25.94, 23.67; 5.93, 19.63, 16.48; 15.22, 12.94, 13.98; 9.98, 9.62, 17.70; 15.26, 7.74, 8.17; 13.10, 4.32, 5.06, P<0.05). Compared to PQ model group, the expression of MMP-2,TIMP-1, MMP-2 mRNA and TIMP-1 mRNA in SDS treatment group at 6 hours, 24 hours and 72 hours were significantly decreased (t=12.71, 13.25, 12.46; 3.18, 6.31, 7.20; 5.24, 4.36, 4.37; 2.16, 3.42, 3

  12. Piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression.

    Science.gov (United States)

    Zhang, Jian; Zhu, Xiaobing; Li, Hengyuan; Li, Binghao; Sun, Lingling; Xie, Tao; Zhu, Ting; Zhou, Hong; Ye, Zhaoming

    2015-01-01

    The piperidine alkaloid piperine, a major ingredient in black pepper, inhibits the growth and metastasis of cancer cells both in vivo and in vitro, although its mechanism of action is unclear. Furthermore, its anticancer activity against osteosarcoma cells has not been reported. In this study, we show that piperine inhibited the growth of HOS and U2OS cells in dose- and time-dependent manners but had a weaker effect on the growth of normal hFOB cells. Piperine inhibited osteosarcoma cell proliferation by causing G2/M phase cell cycle arrest associated with decreased expression of cyclin B1 and increased phosphorylation of Cyclin-dependent kinase-1(CDK1) and checkpoint kinase 2 (Chk2). In addition, piperine treatment inhibited phosphorylation of Akt and activated phosphorylation of c-Jun N-terminal kinase (c-JNK) and p38 mitogen-activated protein kinase (MAPK) in HOS and U2OS cells. Piperine induced colony formation in these two cell types. We proved that piperine could suppress the metastasis of osteosarcoma cells using scratch migration assays and Transwell chamber tests. Moreover, gelatin zymography showed that piperine inhibited the activity of matrix metalloproteinase (MMP)-2/-9 and increased the expression of tissue inhibitor of metalloproteinase (TIMP)-1/-2. Taken together, our results indicate that piperine inhibits proliferation, by inducing G2/M cell cycle arrest, and the migration and invasion of HOS and U2OS cells, via increased expression of TIMP-1/-2 and down-regulation of MMP-2/-9. These findings support further study of piperine as a promising therapeutic agent in the treatment of osteosarcoma.

  13. Effect of Polypeptide Extract from Scorpion Venom on MMP2 and MMP9 Expression in Leukemia -NOD/SCID Mice%蝎毒多肽提取物对白血病NOD/SCID小鼠MMP2、MMP9表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨文华; 郝征; 杨向东; 史哲新; 于文俊; 吕俊秀

    2009-01-01

    Objective: To investigate the effect of polypeptide extract from scorpion venom (PESV) on the matrix metalloproteinase2(MMP2)and matrix metalloproteinase9(MMP9)expression in leukemia-NOD/SCID mice, and the intervention mechanism of PESV in the multiplication and infiltration of leukemic cells thereof. Methods: In order to establish the animal model of outer marrow infiltration of human leukemia,bone marrow mononuclear cells of leukemia patients, irradiated 270 cGy on body by ~(137)Cs, were injected into NOD/SCID mice. The mice were randomly divided into five groups. The groups I, II and III were treated with different concentrations of PESV. Group Ⅳ was the model group injected by the normal saline solution. GroupⅤ was taken as control. The peripheral white blood cell count and blood smear were observed in groups. All of the mice were killed after four-week observation and MMP2 and MMP9 expressions were examined using Real time PCR method. Results: The expression levels of MMP2 and MMP9 were significantly lower in group I, group II and group III than that of the model group(P < 0.05). The expression levels of MMP2 and MMP9 were related to the concentration of PESV. Moreover, the peripheral white blood cell count and blood smear were more normal in mice treated with PESV than those of mice of model group. Conclusion: PESV inhibited the overexpression of MMP2 and MMP9 in leukemia-NOD/SCID mice, which significantly inhibited the multiplication and infiltration of leukemic cells.%目的:观察蝎毒多肽提取物(PESV)对白血病NOD/SCID小鼠基质金属蛋白酶(MMP)2、MMP9表达的影响,探讨PESV对白血病细胞外基质降解和髓外浸润的干预机制.方法:首先选取急性白血病患者骨髓单个核细胞注入经过铯-137源照射的NOD/SCID小鼠体内,建立人白血病NOD/SCID小鼠髓外浸润模型;再将实验小鼠随机分组,Ⅰ组、Ⅱ组、Ⅲ组分别注射不同浓度的PESV,Ⅳ组为模型组注射生理盐

  14. Snail、E-cadherin和MMP-2在I型子宫内膜癌中的表达及临床意义%Expression of Snail, E-cadherin and MMP-2 in type I endometrial carcinoma and its clinicopathological significance

    Institute of Scientific and Technical Information of China (English)

    潘洪琳; 冯振中

    2013-01-01

    Objective To investigate the expression of Snail, E-cadherin and matrix metal oproteinase-2 (MMP-2) in pa-tients with type I endometrial carcinoma and its clinicopathological significance. Methods Tissue microarray and immunohisto-chemical staining were performed to evaluate Snail, E-cadherin, and MMP-2 expression in 58 cases of endometrial carcinoma, 17 cases of atypical hyperplasia and 21normal endometrial samples. The correlation between these three markers with clinico-pathological features were examined. Results The expression of Snail, E-cadherin and MMP-2 proteins was significantly changed as lesions progressed from normal endometrium through atypical hyperplasia to carcinoma, (P<0.01). In addition, in-creased expression of Snail was tightly associated with FIGO stage and lymph node metastasis. Down-regulated expression of E-cadherin protein showed a significantly correlation with myometrial invasion and lymph node metastasis (P<0.05). Similarly, MMP-2 protein also correlated with lymph node metastasis(P<0.05). In primary endometrioid adenocarcinoma, there was a sig-nificant negative association of Snail with E-cadherin expression(r=-0.259, P=0.049), while the expression of Snail was positively correlated with MMP-2 (r=0.447, P<0.01). Conclusion Snail and MMP-2 expression is up-regulated and E-cadherin expres-sion down-regulated in endometrial carcinoma, and detection of these three markers may predict the potential malignancy and tumor behavior.%  目的探讨子宫内膜样腺癌组织中转录因子Snail、上皮钙黏附素(E-cadherin)和基质金属蛋白酶2(MMP-2)的表达关系,研究Snail促进子宫内膜癌侵袭转移的机制及临床意义。方法采用免疫组化方法,结合组织芯片技术,检测58例I型子宫内膜癌、17例内膜不典型增生、21例正常内膜组织中Snail、E-cadherin和MMP-2的表达水平,分析3种蛋白表达之间的相关性及与临床病理因素的关系。结果Ⅰ型子宫内膜癌组织中存在Snail和MMP

  15. The activation of TLR7 regulates the expression of VEGF, TIMP1, MMP2, IL-6, and IL-15 in Hela cells.

    Science.gov (United States)

    Li, Lei; Cheng, Feng-Wei; Wang, Fang; Jia, Bo; Luo, Xin; Zhang, Sheng-Quan

    2014-04-01

    Toll-like receptors (TLRs) play important roles in activation of immunoreaction and tumor development. Toll-like receptor 7 (TLR7), one of the TLRs binding with single-stranded RNA, activates intracellular pathways and stimulates the release of proinflammatory cytokines, chemokines. In this study, we investigated the impact of the TLR7-signaling pathway on the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2), tissue inhibitor of metalloproteinase 1 (TIMP1), interleukin 6 (IL-6), and interleukin 15 (IL-15), which have been testified to refer to the immunomodulating and tumor progression. We confirmed that the TLR7 was expressed by Hela cells, despite the abundance was weak. Gardiquimod, one of the TLR7 ligands, can promote these five genes expression in varying degrees. After stimulating with gardiquimod, the expression of the IL-15V1, 3 increased about 4.5 times on RNA level, the other expression was only up-regulated about 2 times. We also discovered that gardiquimod could activate the MAPK/ERK- and PI3K/AKT-signaling pathways, and the specific inhibitors studies indicate that, the effect of gardiquimod on these genes expression is mainly or partially dependent on the activation of these two signaling pathways. To sum up, the activation of TLR7 signaling pathway may modulate some genes expression in Hela cells and may contribute to the pathogenesis of the cervical cancer.

  16. Study on Lichong Decoction on the Expression of MMP - 2 and TIMP - 2 in Human Uterine Leiomyoma Cells%理冲汤调控人子宫肌瘤细胞 MMP -2、TIMP -2表达的研究

    Institute of Scientific and Technical Information of China (English)

    张武芳; 郑九波; 李冬华; 钱睿亚; 许昕; 黄玉华; 韩虹娟; 朱丽娟

    2015-01-01

    目的:研究理冲汤调控人子宫肌瘤细胞内基质金属蛋白酶-2(MMP -2)及其抑制物(TIMP -2)的表达。方法进行人子宫肌瘤细胞原代、传代培养及鉴定后,加入理冲汤含药动物血清干预,电镜观察人子宫肌瘤细胞微观结构的改变,蛋白质印迹(Western Blotting)技术观察 MMP -2以及 TIMP -2在人子宫肌瘤细胞内的含量与表达。结果电镜显示,与空白对照组比较,理冲汤组细胞排列基本正常,细胞器基本接近正常,线粒体增生肥大减轻,胶原纤维排列基本规则,增生不明显;Western Blotting 显示,与空白对照组比较,理冲汤组的 MMP -2表达显著降低(P ﹤0.05,P ﹤0.01),而 TIMP -2的表达显著升高(P ﹤0.05)。结论理冲汤具有抑制体外人子宫肌瘤细胞生长的作用,其机制可能与降低人子宫肌瘤细胞中 MMP -2的表达,以及提高人子宫肌瘤细胞中 TIMP -2的表达有关。%Objective To investigate Lichong Decoction on the expression of Matrix metalloprotein-ase - 2(MMP - 2)and Tissue inhibitors of metalloproteinase - 2( TIMP - 2)in human uterine leiomyoma cells. Methods The primary culture and subculture of the human uterine leiomyoma cells were performed and identified. The cells were treated with Lichong Decoction. Electron microscope was used to observe micro-structure changes in the uterine leiomyoma cells. Western blotting was used to measure the expression of MMP - 2 and TIMP - 2 in human uterine leiomyoma cells. Results The transmission electron microscope pathological examination showed cells of Li Chong Decoction group arranged basically normal,cellular organs were quite close to the normal,hyperplasia and hypertrophy of chondriosome were reduced,collagen fibers ar-ranged basically regularly,hyperplasia was not obvious. Western blotting showed the expression of MMP - 2 significantly was reduced in Lichong Decoction group(P ﹤ 0. 05,P ﹤ 0. 01). However

  17. Effect of gene CTGF transfection on the expression of MMP-2 and MMP-9 and proliferation in human cervical cancer cells%CTGF基因转染对宫颈癌细胞MMP-2、MMP-9表达及细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    肖蔚; 焦霞; 钱华; 崔永安; 林梅; 王薇; 周彤敏; 窦荣荣; 于鸿

    2012-01-01

    Objective: To investigate the effect of connective tissue growth factor ( CTGF ) on the proliferation in human cervical cancer cell line Hela, with a focus on the expression of matrix metalloproteinase-2( MMP-2 ) and matrix metalloproteinase-9( MMP-9 ), and explore the underlying mechanism for the role of CTGF in the development of cervical cancer. Methods: pcDNA3. 0-CTGF and pcDNA3.0 were transfected into Hela cells through lipofectamine and positive clones which were screened by G418. Fluorescence quan-titive polymerase chain reaction( FQ-PCR ) and Western blot were employed to identify mRNA and protein expression of CTGF in Hela cells, respectively. The expression of MMP-2 and MMP-9 in positive clones was detected by FQ-PCR and Western blot. Cell viability was assessed by dimethylthiazoldiphenyl-tetrazolium-bromide ( MTT ) method. Results: Positive clone C-16 with CTGF over-expression were successfully established. Compared with non-transfected control group, the expression of MMP-2 and MMP-9 in C-16 were increased significantly,and the proliferation level of C-16 was increased significantly. Conclusion: CTGF transfection could effectively enhance the expression of MMP-2 and MMP-9 and the proliferation in Hela cells which suggested a potential role for CTGF in gene therapy of cervical cancer.%目的:研究结缔组织生长因子(connective tissue growth factor,CTGF)基因对人宫颈癌Hela细胞基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)表达及细胞增殖的影响,探讨CTGF在宫颈癌侵袭和转移中的作用机制.方法:经脂质体介导将含有CTGF重组表达质粒转染人宫颈癌Hela细胞株,用G418筛选阳性细胞克隆及实时荧光定量PCR、蛋白质印迹鉴定;采用实时荧光定量PCR和蛋白质印迹法检测阳性克隆细胞MMP-2及MMP-9的表达;噻唑盐(MTT)比色法检测阳性细胞克隆的增殖活性.结果:成功建立稳定高表达CTGF的阳性Hela细胞克隆,证实其MMP-2、MMP-9表达及细

  18. 五味子乙素对染矽尘大鼠肺组织MMP-2和TIMP-2蛋白表达的动态影响%Effect of Schisandrin B on Dynamic Change of MMP-2 and TIMP-2 Expression in Rat Lungs Exposed to Silica

    Institute of Scientific and Technical Information of China (English)

    郭民; 樊林花; 陈朝阳; 刘田福

    2012-01-01

    To investigate the effect of schisandrin B on expression and significance of matrix metalloprotein-ase(MMP-2) and tissue inhibitor of matrix metall oproteinase(TIMP-2) protein in silica induced pulmonary fibrosis model,the lung injury model was established by a single intratracheal injection of silica. From the first day of exposure of silica,the rats were treated with Sch-B and sacrificed on 3,7,14 and 28 d and lungs were collected. The histopathological of the lungs were observed by HE staining and changs of collagen fibers in the lungs were observed by Masson staining. The MMP-2 and TIMP-2 protein expression were determined by ELISA. The results show that compared with control group,Sch-B improved fibrosis of lungs and reduced collagen fibers, Sch-B could inhibit expression of MMP-2 protein in model rats at every time points,and improve expression of TIMP-2 at the initial stage of rat lungs exposed to silica. Sch-B can inhibit MMP-2 induced lung injury. Sch-B inhibited expression of TIMP-2 at the final stage and reduced pulmonary fibrosis.%为研究五味子乙素(Sch-B)对二氧化硅致大鼠矽肺中基质金属蛋白酶(MMP-2)和其抑制物基质金属蛋白酶组织抑制因子(TIMP 2)的作用,采用暴露式气管内注入SiO2混悬液法建立大鼠矽肺模型,染毒后1d开始灌胃给予Sch-B干预治疗,药物干预3d、7d、14d和28 d后处死取其肺组织.应用HE、Masson染色法观察肺组织病理改变及肺组织胶原纤维变化;通过ELISA法对大鼠肺组织中不同时间点的MMP-2、TIMP-2蛋白的表达情况进行了研究.结果表明:Sch-B对矽肺组织纤维化病变有明显的改善,胶原纤维明显减少.Sch-B对二氧化硅致大鼠矽肺中不同时间点肺组织MMP-2的表达均有一定程度的抑制作用,早期肺泡炎时可一过性提高TIMP-2的表达,起到抑制MMP-2对肺组织损伤的作用,后期抑制TIMP-2的表达,减缓肺组织纤维化的发生.

  19. Observation the inhibitory effect and expression of MMP -2, CD44v6 of common turmeric among tumor-bearing nude mice%温郁金对荷肿瘤裸鼠抑瘤作用和MMP -2、CD44v6表达影响的观察

    Institute of Scientific and Technical Information of China (English)

    王光亮; 张俊会

    2012-01-01

    Objective To study the inhibitory effect of common turmeric and the expression of MMP - 2 and CD44v6 proteins in human gastric SGC -7901 cell, explore the possible mechanisms on gastric cancer metastasis. Method Established nude mouse orthotopic transplantation mode of SGC - 7901 and then randomly divided the nude mouse into control group and common turmeric group. The tumor growth and metastasis were observed, the expression of MMP - 2 and CD44v6 proteins in the tumor tissue were detected by immunohisto-chemistry. Results The rate of successfully orthotopic transplantation was 100%. The weight of the tumors in common turmeric group was (2.73 ±0.92) g, in control group was (4. 09 ± 1.17) g, there was statistical significance between the two group (P <0.05) , The inhibitory rate of common turmeric group was 33. 25%. The metastasis of cavitas peritonealis, liver and lymph node in common turmeric group were significantly lower than those of control group (P < 0. 05) . Meanwhile, we found that the positive rates of MMP - 2 and CD44v6 expression in the common turmeric group were obviously lower than that in control group (P<0.05) . Conclusions Common turmeric can inhibit gastric cancer growth and metastasis in orthotopic transplantation model of nude mice, the mechanism might be related to down - regulation of MMP - 2 and CD44v6 expression.%目的 观察温郁金对胃癌细胞抑制作用和MMP-2、CD44v6蛋白表达的影响,探讨其抗胃癌细胞转移的作用机制.方法 以SGC - 7901胃癌细胞株建立胃癌裸鼠原位移植瘤模型,将裸鼠随机分为对照组(0.9%氯化钠溶液)及实验组(温郁金水煎剂).观察裸小鼠胃癌种植后肿瘤生长及转移灶情况,用免疫组化法检测2组肿瘤组织中MMP-2和CD44v6蛋白的表达.结果 2组荷瘤鼠胃壁均有肿瘤生长,荷瘤率100%,对照组瘤重(4.09±1.17) g,实验组瘤重(2.73±0.92) g(与对照组比较P<0.05),抑瘤率为33.25%;实验组肝、腹腔和淋巴结转

  20. Inhibitory Effect of Erhuang Jieyu Tang on Cell proliferation and MMP-2 Expression in HepG2 Cells%二黄解郁汤对肝癌HepG2细胞生长抑制及MMP-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    李俊立; 丁月妮

    2012-01-01

    目的:观察二黄解郁汤对肝癌细胞生长抑制作用及对MMP-2表达的影响.方法:分别用不同浓度二黄解郁汤作用不同时间于人肝癌HepG2细胞,以MTT法观察并计算IC50值,荧光显微镜检测HepG2细胞生长情况,Western blot检测HepG2细胞中MMP-2蛋白的表达.结果:二黄解郁汤对HepG2细胞作用24,48和72 h的IC50分别为600,550,150 μg/mL;荧光显微镜下可见细胞内药物绿色荧光,且细胞数量随药物浓度增加而减少;Western blot结果表明,经100,200,400 μg/mL的二黄解郁汤干预的细胞中MMP-2蛋白的表达分别占空白组的(77.3±4.84)%、(56.25±3.31)%、(33.21±7.26)%,呈剂量依赖性下降(P<0.01).结论:二黄解郁汤对肝癌细胞具有明显的抑制作用,其作用可能与抑制MMP-2蛋白的表达有关.%Objective To investigate the inhibitory effect of cell proliferation and expression of MMP-2 by Erhuang Jieyu Tang in HepG2 cells. Methods A serious concentration of 0,40,80,100,200,400,800μg/mL of Erhuang Jieyu Tang were administered on human hepatocellular carcinoma HepC2 cells for 24,48,72 h, IC50 value was detected by MTT. The viability of HepC2 cells with different concentration of Erhuang Jieyu Tang (0,100,200,400μg/mL) for 48 h was detected by fluorescence microscopy directly; the expression of MMP-2 in HepG2 with Erhuang Jieyu Tang was determined by Western blot. Results The IC50 value of HepG2 cells treated with Erhuang Jieyu Tang for 24 h, 48 h and 72 h were 600,550,150 μg/mL, respectively. The viable cells were dramatically decreased; and data also showed that compared with cells without treated, the rate of level of MMP-2 in HepG2 with Erhuang Jieyu Tang were (77. 3 ±4. 84)% , (56. 25 ± 3. 31)% , (33.21 ±7.26)%, in a dose-dependent manner (P<0.01). Conclusion Erhuang Jieyu Tang could inhibit the proliferation of HepG2 cells,which may correlate with the inhibitory effect on of MMP-2 protein expression.

  1. Expression and clinical significance of MMP-2 and TIMP-2 in liver tissues of patients with mild chronic hepatitis B%轻度慢性乙型肝炎患者肝组织中MMP-2和TIMP-2的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    诸葛璐; 潘陈为; 林巍; 方佩佩; 方周溪; 周光耀; 吕夕明; 金玲湘

    2013-01-01

    目的 探讨轻度慢性乙型肝炎(CHB)患者肝组织中的基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶抑制剂-2(TIMP-2)的表达及临床意义.方法 选取2006年12月至2011年12月温州医学院附属第二医院感染内科收治入院的慢性HBV感染者68例为研究对象,将其分为轻度慢性乙型肝炎(CHB)组(35例)和慢性HBV携带组(33例).采集患者血清,行HBV血清学标志物、HBVDNA、肝纤维化血清学指标检测及肝穿刺活检,光镜下观察肝组织.采用免疫组织化学染色法检测MMP-2和TIMP-2的表达,并进行阳性表达评分及肝组织纤维化分级.用SPSS 17.0软件进行统计学分析.结果 轻度CHB组和慢性HBV携带者组血清肝纤维化指标透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型胶原(PC Ⅲ)和Ⅳ型胶原(CⅣ)的差异无统计学意义(t=1.35,1.65,1.88和1.89,P>0.05).轻度CHB组肝组织中MMP-2和TIMP-2评分分别为(4.42±1 37)和(3.89±1.12)分,慢性HBV携带组分别为(3.61 ±1.23)和(3.31±1.07)分,差异有统计学意义(t=2.56和2.18,P<0.05).CHB组的MMP-2/TIMP-2比值为1.15±0.17,而慢性HBV携带组为1.08-±0.11,两组比较差异有统计学意义(t=2.04,P<0.05).MMP-2和TIMP-2评分与纤维化分级的相关系数分别为0.372(P =0.002)和0.439(P =0.000).结论 轻度CHB患者的肝组织中MMP-2和TIMP-2表达增加,且与纤维化分级具有相关性,可用于评估患者肝纤维化的程度.%Objective To investigate the expression and clinical significance of matrix metalloprotein-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 (TIMP-2) in liver tissues of patients with mild chronic hepatitis B.Methods A total of 68 subjects with chronic hepatitis B virus (HBV) infections admitted to the Second Affiliated Hospital of Wenzhou Medical College during December 2006 and December 2011 were enrolled in the study,including 35 cases of mild chronic hepatitis B (CHB) and 33 carriers.Serum samples were collected,and serum HBV markers

  2. 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.

  3. 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.

  4. MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP-2 expression.

    Science.gov (United States)

    Shin, Seung-Shick; Park, Sung-Soo; Hwang, Byungdoo; Kim, Won Tae; Choi, Yung Hyun; Kim, Wun-Jae; Moon, Sung-Kwon

    2016-10-01

    Despite the clinical significance of tumorigenesis, little is known about the cellular signaling networks of microRNAs (miRs). Here we report a new finding that mir‑106a regulates the proliferation, migration, and invasion of bladder cancer cells. Basal expression levels of mir‑106a were significantly lower in bladder cancer cells than in normal urothelial cells. Overexpression of mir‑106a suppressed the proliferation of bladder cancer cell line EJ. Transient transfection of mir‑106a into EJ cells led to downregulation of ERK phosphorylation and upregulation of p38 and JNK phosphorylation over their levels in the control. Flow cytometry analysis revealed that mir‑106a-transfected cells accumulated in the G1-phase of the cell cycle, and cyclin D1 and CDK6 were significantly downregulated. This G1-phase cell cycle arrest was due in part to the upregulation of p21CIP1/WAF1. In addition, mir‑106a overexpression blocked the wound-healing migration and invasion of EJ cells. Furthermore, mir‑106a transfection resulted in decreased expression of MMP-2 and diminished binding activity of transcription factor Ets-1 in EJ cells. Collectively, we report the novel mir‑106a-mediated molecular signaling networks that regulate the proliferation, migration, and invasion of bladder cancer cells, suggesting that mir‑106a may be a therapeutic target for treating advanced bladder tumors.

  5. 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.

  6. Immunoexpression of matrix metalloproteinase-2 (MMP-2) in epithelial ovarian cancers (EOCs)

    Institute of Scientific and Technical Information of China (English)

    Ibrahim A Abdelazim; Mohannad Lutfi Abu faza; Mohammed Al-Kadi

    2013-01-01

    Objective: To evaluate the relation between matrix metalloproteinase-2 (MMP-2) expression and the clinical and/or pathological parameters of the epithelial ovarian cancers (EOCs). Methods: Forty-two (42) patients with EOCs diagnosed after histopathological examination of the specimens were included in this study. The pathological specimens were additionally stained by immunoperoxidase technique for MMP-2 using a monoclonal antibody against activated MMP 2. The staining intensity of MMP-2 was correlated with the clinical and pathological parameters of the studied cases, including patient's age, surgical stage, histological grade, omental, and lymph node metastasis. Results: The studied cases of EOCs were classified according to the intensity or the degree of MMP-2 expression, as; seven cases (16.7%) negative, eighteen cases (42.8%) weak, seven cases (16.7%) moderate and ten cases (23.8%) intense for MMP-2 staining. There was a significant positive correlation between MMP-2 expression and the histological grades and the surgical stages of the studied EOC (r <1, P<0.05), while, there was no significant relation between MMP-2 expression and the histopathological types of the studied EOCs. MMP-2 expression was significantly high in EOCs with ascites, omental, distant and uterine metastasis, while, there was no significant relation between MMP-2 expressions and lymph node metastasis or bilaterality of the EOCs. Conclusions: MMP-2 expression was associated with advanced, aggressive EOCs and there was direct relation between expression of MMP-2 and degree of invasiveness and metastasis of EOCs.

  7. 高糖对MMP-2与TIMP-2的表达及血管平滑肌细胞增殖的影响%Effects of high glucose on MMP-2 and TIMP-2 expressions and proliferation of vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    路艳; 张春艳; 王聪霞; 张岩; 朱锦云; 高艳华; 丁法明; 陈俊亮

    2012-01-01

    目的 探讨高糖作用下大鼠胸主动脉平滑肌细胞基质金属蛋白酶-2(MMP-2)及其组织抑制剂-2(TIMP-2)的表达情况及高糖对血管平滑肌细胞(VSMCs)增殖的影响.方法 大鼠胸主动脉平滑肌细胞培养及传代后,分为正常浓度葡萄糖组(NG组,5.5mmol/L葡萄糖)、甘露醇高渗对照组(5.5 mmol/L葡萄糖+19.5 mmol/L甘露醇)、高浓度葡萄糖组(HG组,25 mmol/L葡萄糖)和GM6001组(25 mmol/L葡萄糖+5μmol/L GM6001),在4组不同的培养环境下分别培养72h后,用RT-PCR技术检测MMP 2与TIMP-2的表达情况,同时用MTT比色法检测4种不同培养环境下VSMCs的增殖情况.结果 HG组与NG组相比,MMP-2与TIMP-2 mRNA的表达增强,差异具有统计学意义(P<0.01),甘露醇高渗对照组、GM6001组与NG组相比,MMP- 2与TIMP-2 mRNA的表达差异无统计学意义(P>0.05);HG组与NG组相比,MMP-2与TIMP-2 mRNA的相对表达量的比值显著增加,差异具有统计学意义(P<0.01),甘露醇高渗对照组、GM6001组与NG组相比差异无统计学意义(P>0.05);HG组各时间点细胞增殖与NG组相比差异具有统计学意义(P<0.05),而GM6001组、甘露醇高渗对照组各时间点的细胞增殖与NG组相比差异无统计学意义(P>0.05).结论 高浓度葡萄糖促进血管平滑肌细胞增殖,这可能是通过MMP-2与TIMP-2表达失衡介导的.%To investigate the effect of high glucose on expressions of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) as well as on the proliferation of vascular smooth muscle cells (VSMCs). Methods After being cultured and passaged, the VSMCs were divided into four groups and cultured in four different culture conditions for 72 hours, respectively:normal glucose group (NG group, 5. 5 mmol/L Glu), mannitol group (5.5 mmol/L Glu + 19. 5 mmol/L mannitol), high glucose group (HG group, 25 mmol/L Glu) and GM6001 group (25 mmol/L Glu + 5 emol/L GMG001). Then, the expressions of MMP-2 and

  8. 牛蒡苷元通过调节 MMP-2,MMP-9表达抑制增生性瘢痕的形成%Arctigenin Preventsthe Formation of Hypertrophic Scars by Reducing the Expression of MMP-2 and MMP-9

    Institute of Scientific and Technical Information of China (English)

    杜志超; 王姗; 卢兹凡; 王玉琨; 汪莉

    2014-01-01

    Objective To investigate the effects of arctigenin on the formation of hypertrophic scars and the possible mechanism. Methods Twenty-five rabbits were randomly divided into five groups: control group, model group, 0. 5 mg / mL arctigenin group, 2 mg / mL arctigenin group and 6 mg / mL arctigenin group. Hypertrophic scars were induced on the ventral surface of rabbit ears and treated with arctigenin at different doses. The wound healing and hyperplasia of the scars were ob-served. The scar tissues were removed for histopathological detection with HE staining, Sirius red staining and Masson staining and for detection of expression of MMP-2 and MMP-9 with Western blotting 6 weeks after treatment. Results HE staining, Sirius red staining and Masson staining showed that arctigenin (2 mg / mL) could significantly inhibit the hyperplasia of the scars. The scars were flatter, the number of fibroblasts and the density of collagen were less in the arctigenin-treated groups than in the model group. Western blotting showed that the expression levels of MMP-2 and MMP-9 were significantly decreased in 2 mg / mL arctigenin group. Conclusion Arctigenin may prevent the formation of hypertrophic scars by reducing the expression of MMP-2, MMP-9 and it may be used to treat hyperplastic scars.%目的:观察牛蒡苷元对增生性瘢痕(hypertrophic scar)形成的作用,并探讨其抑制增生性瘢痕形成的机制。方法新西兰大耳兔25只,将其分为对照组( A 组),模型组(B 组),牛蒡苷元治疗组(0.5 mg/ ml)(C 组),牛蒡苷元治疗组(2 mg/ ml)(D 组),牛蒡苷元治疗组(6 mg/ ml)(E 组),在兔耳腹侧面建立增生性瘢痕模型,术后按组别进行相应处理,观察创面愈合和瘢痕的增生情况。用药后在第6周取材,进行 HE 染色,天狼猩红染色和 Masson 染色,并用 Western 印迹检测 MMP-2, MMP-9表达情况。结果 HE 染色,天狼星红染色和 Masson 染色结果表明,牛蒡苷元治疗组(2 mg/ ml)可以明显抑制增

  9. MMP-2和 TIMP-2在多柔比星肾病大鼠中的表达及卡托普利对其影响的研究%MMP-2 and TIMP-2 expression in doxorubicin nephropathy in rats and studied the impact of captopril

    Institute of Scientific and Technical Information of China (English)

    安辉军

    2014-01-01

    Objective To explore the MMP - 2 and TIMP - 2 expression in doxorubicin nephropathy in rats and captopril on the im-pact of nephropathy rats. Method Male SD rats as the research object,through the tail vein injection doxorubicin method nephrotic syn-drome model was established,the control injection of saline solution. In experiment 7,14,28,and 42 days testing rats,24 hours urinary protein level and MMP - 2 and TIMP - 2 levels in serum and kidney tissue were determined by ELISA. And put to death in the rat,kid-ney tissues did light microscope examination,to observe changes in renal morphology of rates. 42 days with the conventional method to de-tect the serum triglyceride(TG),total cholesterol(TC),albumin(propagated),total protein(TP),creatinine(Scr),urea nitrogen ( BUN). Results ①at different times for 24 h urine protein quantitative treatment group was obviously lower,and compared with normal group and model group had significant difference( P﹤ 0. 01). ②total cholesterol,triglycerides,treatment group was obviously lower in different periods at the same time the normal group,model group( P﹤ 0. 01);Albumin,total protein was significantly higher than the lat-ter two( P﹤ 0. 01);Similar creatinine and urea nitrogen content between the 3 groups( P﹥ 0. 05). ③the application in different peri-ods after captopril treatment group serum and kidney tissue concentrations of MMP - 2 and at the same time model group than lower( P﹤0. 01),and 24 h urine protein between quantitative and were positively correlated(r = 0. 859,P﹤ 0. 01 and r = 0. 902,)and TIMP -2 with the model group than higher( P﹤ 0. 01). Conclusion MMP - 2 and TIMP - 2 with nephrotic syndrome( PNS)is closely related to the occurrence and development. Captopril has the effect of degradation of MMP - 2.%目的:探讨MMP-2和TIMP-2在多柔比星肾病大鼠中的表达及卡托普利对其影响。方法:以雄性SD大鼠为研究对象,通过尾静脉注射多柔比星的方法建立肾病

  10. Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chandrashekar, Naveenkumar; Selvamani, Asokkumar; Subramanian, Raghunandhakumar; Pandi, Anandakumar; Thiruvengadam, Devaki, E-mail: devakit@yahoo.co.uk

    2012-05-15

    -α, IL-1β, i-NOS and NF-κBp65 at protein levels. ► BE modulates the expressions of MMP-2, MMP-9 and COX-2 at protein and mRNA levels. ► BE decreases LPO levels and enhances antioxidant status.

  11. The Expression and Clinical Significance of C-erbB-2, MMP-1,MMP-2, MMP-7 and MTA1 in Esophageal Cancer of the Kazak%C-erbB-2、MMP-1、MMP-2、MMP-7和MTA1在哈萨克族食管癌中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    李秀梅; 王洪江; 陈艳; 庞作良; 李卉; 姜孝芳; 古丽努尔·木哈依; 谌宏鸣; 李惠武

    2011-01-01

    通过观察C-erbB-2、MMP-1、MMP-2、MMP-7和MTA1 5个基因在哈萨克族食管癌组织中的表达,探讨其侵袭转移相关因子在新疆哈萨克族食管癌组织的表达和临床意义.采用RT-PCR方法检测75例哈萨克族食管癌标本中这5个基因的mRNA表达水平,分析它们与临床病理特征的关系.结果显示,5个基因在哈萨克族食管癌组织中表达较正常组织增高,达到差异显著(P<0.05);MMp-2、MMP-7、MTA1基因的表达与淋巴结转移相关(P<0.05),MMP-1、MMP-7基因的表达与临床分期正相关(P<0.05):C-erbB-2与MTA1、MMP-2与MTA1、MMP-7与MTA1、MMP-7与MMP-1、MMP-1与MTA1基因的表达差异高度一致(P<0.01).由此得出,这5个基因表达上调在哈萨克族食管癌的发生发展过程中协同发挥作用;MMP-2、MMP-7、MTA1可能是哈萨克族食管癌发生侵袭、转移的主导因素.%The expressions of C-erbB-2, MMP-1.MMP-2, MMP-7 and MTA 1 in esophageal cancer tissue and normal tissue among the Kazak are studied and the relationshlp between their expressions and clinical pathological feature is investigated. The expression of C-erbB-2, MMP-1, MMP-2, MMP-7 and MTA 1 gene mRNA were detected by using RT-PCR method in 75 esopthageal cancer specimens of the Kazak. The results show that the positive rates of C-erbB-2, MMP-1, MMP-2, MMP-7 and MTA 1 in cancer tisssue are higher than that of normal tissues (p<0.05). While the expression mRNA level of MMP-2, MMP-7 and MTA 1 is significantly related to the lymphnode metasis,And the expression mRNA level of MMP-1 MMP-7 is sigaificantly related to the TNM stages (P<O.05). Kappa analysis indicates that the expressions between C-erbB-2 and MTA 1, MMP-2 and MTA 1, MMP-7 and MTA 1, MMP-7 and MMP-1,MMP-1 and MTA 1 in the Kazak's esophageal cancer are positively related (k=O.624, 0.367, 0.564, 0.275.0.384. P<0.0l) with each other The conclusion shows that the over expression of C-erbB-2, MMP-1, MMP-2, MMP-7 and MTA 1 gene could play the

  12. Impacts of blood glucose fluctuation on renal pathologic changes and IGF-1, MMP-2 expression%血糖波动对2型糖尿病大鼠肾组织病理改变及IGF-1 、MMP-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    王桂霞; 周冬梅; 李伟

    2014-01-01

    Objective To investigate the impacts of blood glucose fluctuation on renal pathologic changes and IGF-1,MMP-2 expression.Methods Forty five male Sprague-Dawley (SD) rats were divided into two groups according to random number table method:experimental group (DM group,n =35) and normal control group(N group,n =10).Streptozotocin (35 mg/kg) was used to induce diabetes.SD rats were fed with high sugar and high fat diet for 4 weeks,and then were divided into fluctuating blood glucose group(F group,n =17) and continuous high blood glucose group (C group,n =17).The rats in F group were given intraperitoneal injection of insulin and glucose at different time points every day.The same volume of physiological saline was given to rats in C and N group.High sugar and high fat diets were maintained in rats in F and C group,while ordinary diet were given to the rats in N group.12 weeks later,24 hours urine protein,blood urea nitrogen,serum creatinine were determined,HE and PAS staining were used to observe the renal morphology,and electron microscopy was applied to observe the ultrastructural change of kidney.Expression of IGF-1 and MMP-2 were determined by immunohistochemistry.Results Rats of F group suffered more serious blood glucose fluctuation with CV value significantly higher than that in rats of C and N group.No significant difference of HbA1c between rats of F and C group,while both higher than rats of N group.Compared with C group,rats in F group showed higher 24 hours urinary protein,kidney hypertrophy index,glomerulosclerosis index,thicker of glomerular basement membrane,and greater elevation of IGF-1 expression,while less MMP-2 expression(all P<0.05).Conclusions Blood glucose fluctuation may aggravate diabetic kidney damage,the mechanism of which may be related to the upregulation of IGF-1,while downregulation of MMP-2.%目的 观察血糖波动对2型糖尿病大鼠肾组织病理及胰岛素样生长因子(IGF)-1、基质金属蛋白酶(MMP)-2

  13. Expression Significance of CD147 and MMP-2 in Tissues of Chronic Cholecystitis and Gallblad-der Carcinoma%CD147和MMP-2在胆囊癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    矫树华; 温艳惠

    2015-01-01

    【目的】探讨细胞外基质金属蛋白酶诱导因子(CD147)和基质金属蛋白酶2(MMP‐2)在胆囊癌组织中的表达及意义。【方法】采用免疫组织化学法检测30例慢性胆囊炎和21例胆囊癌患者组织中CD147和M M P‐2的表达,并分析其临床意义。【结果】21例胆囊癌组织中 CD147和 M M P‐2的阳性表达率分别为71.4%(15/21)和76.2%(16/21),显著高于慢性胆囊炎组织中的表达13.3%(4/30)和23.3%(7/30)( P <0.01);CD147和M M P‐2的阳性表达与胆囊癌的临床分期和淋巴结转移显著相关( P <0.05),且胆囊癌中CD147与MMP‐2的阳性表达呈正相关( r =0.631,P =0.002)。【结论】CD147和MMP‐2在胆囊癌组织中的阳性表达与其临床分期和淋巴结转移相关,CD147可能通过与M M P‐2的相互作用共同参与调控胆囊癌的进展与转移。%[Objective] To explore the expressions of CD147 and matrix metalloprotease‐2 (MMP‐2) in tissues of chronic cholecystitis and gallbladder carcinoma and examine their clinical significance .[Methods]Immunohistochemistry was used for detecting CD147 and MMP‐2 in 30 chronic cholecystitis tissues and 21 gallbladder carcinoma tissues .And their clinicopathological data were analyzed .[Results] The expressions of CD147 and MMP‐2 was significant higher in 21 gallbladder carcinoma tissues [71 .4% (15/21)& 76 .2% (16/21)] than those in 30 chronic cholecystitis tissues [13 .3% (4/30)& 23 .3% (7/30)]( P<0 .01) .And the pos‐itive expressions of both were correlated with staging and lymph node metastasis ( P<0 .05) .The expressions of CD147 and MMP‐2 had a positive correlation in gallbladder carcinoma ( r =0 .631 ,P =0 .002) .[Conclu‐sion] The expressions of CD147 and MMP‐2 are positively correlated with staging and lymph node metastasis in gallbladder carcinoma .And CD147 may interact with MMP‐2 in regulating the progression of

  14. Adenovirus-mediated Gene Transfer of MMP-2 into Cultured Porcine Trabecular Meshwork Cells

    OpenAIRE

    2012-01-01

    This study aimed to use adenoviral gene transfer to express matrix metalloproteinase (MMP)-2 in cultured porcine trabecular meshwork cells and to evaluate the duration of adenovirus-mediated MMP-2 expression and its enzymatic activity. MMP-2 cDNA was synthesized by ligating three segments of MMP-2 cDNA obtained by reverse transcription-polymerase chain reaction (RT-PCR) with mRNA extracted from mouse lungs. MMP-2 cDNA was inserted into replication-deficient adenoviral vectors. Western blottin...

  15. Increased expression of HIF-1α, VEGF-A and its receptors, MMP-2, TIMP-1, and ADAMTS-1 at the venous stenosis of arteriovenous fistula in a mouse model with renal insufficiency

    Science.gov (United States)

    Misra, Sanjay; Shergill, Uday; Yang, Binxia; Janardhanan, Rajiv; Misra, Khamal D.

    2010-01-01

    Purpose A mouse model of renal insufficiency with arteriovenous fistula (AVF) and venous stenosis was created. We tested the hypothesis that there is increased gene expression of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor- A (VEGF-A) and its receptors (VEGFR-1, -2), matrix metalloproteinase-2 (MMP-2), -9 (MMP-9), tissue inhibitor of metalloproteinase-1, -2 (TIMP-1, -2), and a disintegrin and metalloproteinase thrombospondin-1 (ADAMTS-1) at the venous stenosis. Materials and methods Nineteen male C57BL/6 mice underwent a left nephrectomy and a surgical occlusion of the right upper pole to induce renal insufficiency and characterized in eight mice. Twenty eight days later, an AVF (n=11) was created from the right carotid artery to ipsilateral jugular vein and the mice were sacrificed at day 7 (n=4) and day 14 (n=4). The outflow and control veins were removed for gene expression. Three mice were sacrificed at day 28 for histologic analysis. Results The mean serum blood urea nitrogen remained significantly elevated for 8 weeks when compared to baseline (P<0.05). By day 7, there was a significant increase in the expression of HIF-1α, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein with HIF-1α and TIMP-1 being significantly elevated at day 14 (P<0.05). By day 28, the venous stenosis was characterized by a thickened vein wall and neointima. Conclusions A mouse model of renal insufficiency with AVF was developed which had increased expression of HIF-1α, VEGF-A, VEGFR-1, VEGFR-2, MMP-2, TIMP-1, and ADAMTS-1 at the outflow vein with venous stenosis by day 28. PMID:20598569

  16. Infection of Schistosomiasis japanicum is likely to enhance proliferation and migration of human breast cancer cells:mechanism of action of differential expression of MMP2 and MMP9

    Institute of Scientific and Technical Information of China (English)

    Ya-Ling; Lin; Rakesh; Ramanujum; Shiping; He

    2011-01-01

    Objective:To study whether the infection of Schistosomiasis japanicum(S.japanicum) is related to enhanced proliferation and migration of cancer cells,and the molecular mechanism pertains to cancer cell metastasis in human host.Methods:The gene of S.japanicum glutathione transferase(sjGST) cloned from 5.japanicum was expressed,purified and applied in a series of assays to explore the effect of sjGST on proliferation and migration of MDA-MB-435S,and the expression of MMP2 and MMP9.Immunofluorescence assay for the binding of sjGST to MDA-MB-435S was also carried out.Results:Results showed that sjGST enhanced proliferation and migration in human breast cancer cell MDA-MB-435S signifycantly at 50-200 nM,but did not enhance them in human lung cancer cell A549.Immunofluorescence assay for the binding of sjGST to MDA-MB-435S and A549 showed that GST was readily hound to the breast cancer cells,but showed almost no binding to human lung cancer cells.The assays for gelatinase activity showed that both MMP2 and MMP9 activities were increased significantly in the presence of sjGST(50-200 nM) in MDA-MB-435S, but they were not significant in A549.Conclusions:Our current results show strongly that S. japanicum GST binds to MDA-MB-435S probably via its i’eceptor,and enhances proliferation and migration of the cancer cells by up-regulatory expression of MMP2 and MMP9.

  17. Infection of Schistosomiasis japanicum is likely to enhance proliferation and migration of human breast cancer cells:mechanism of action of differential expression of MMP2 and MMP9

    Institute of Scientific and Technical Information of China (English)

    Ya-Ling Lin; Rakesh Ramanujum; Shiping He

    2011-01-01

    Objective: To study whether the infection of Schistosomiasis japanicum (S. japanicum) is related to enhanced proliferation and migration of cancer cells, and the molecular mechanism pertains to cancer cell metastasis in human host. Methods: The gene of S. japanicum glutathione transferase (sjGST) cloned from S. japanicum was expressed, purified and applied in a series of assays to explore the effect of sjGST on proliferation and migration of MDA-MB-435S, and the expression of MMP2 and MMP9. Immunofluorescence assay for the binding of sjGST to MDA-MB-435S was also carried out. Results: Results showed that sjGST enhanced proliferation and migration in human breast cancer cell MDA-MB-435S signifycantly at 50-200 nM, but did not enhance them in human lung cancer cell A549. Immunofluorescence assay for the binding of sjGST to MDA-MB-435S and A549 showed that GST was readily bound to the breast cancer cells, but showed almost no binding to human lung cancer cells. The assays for gelatinase activity showed that both MMP2 and MMP9 activities were increased significantly in the presence of sjGST (50-200 nM) in MDA-MB-435S, but they were not significant in A549. Conclusions: Our current results show strongly that S. japanicum GST binds to MDA-MB-435S probably via its receptor, and enhances proliferation and migration of the cancer cells by up-regulatory expression of MMP2 and MMP9.

  18. Study on the Expression of MMP-2 and MMP-13 in Human Gingival Fibroblast Cells of Porcelain Fused to Metal Crown%烤瓷冠基底合金影响人牙龈成纤维细胞MMP-2、MMP-13表达实验探讨

    Institute of Scientific and Technical Information of China (English)

    刘丽梅

    2016-01-01

    Objective To observe the effects of different kinds of porcelain fused to metal crown on the expression of MMP-2 and MMP-13 in human gingival fibroblast cells.Methods The preparation of pure titanium and cobalt chromium, nickel chromium alloy and gold extraction, by means of a modiifed tissue to ifbroblast cells were cultured on the gums around, after leaching liquid immersion, were collected on a sample cell supernatant, the expression level of MMP-13 was determined as the sample determination method for ILISA determination. Results The expression of CO Cr alloy and Ni Cr alloy MKMP-13 was higher than the negative control group and experimental group, comparison of various indexes, the difference was statistically signiifcant (P0.05) in the gold and pure titanium alloy group.Conclusion Co Cr alloy and Ni Cr alloy MKMP-13 high expression level, to a certain extent will damage the gingival ifbroblast; gold, pure titanium alloy biocompatibility is good.%目的:观察不同种类烤瓷牙金属基底冠浸提液对人牙龈成纤维细胞中 MMP-2、MMP-13表达水平的影响。方法制备纯钛、钴铬、镍铬和金合金提取液,通过组织块改良的方法来对牙龈周围的纤维细胞进行培养,经过浸提液浸泡之后,分别收集样本上的细胞清液,作为MMP-13表达水平的测定样本,测定方法为ILISA测定法。结果钴铬合金和镍铬合金MKMP-13表达水平高于阴性对照组和其他实验组,各项指标对比,差异有统计学意义(P<0.05);金、纯钛合金组MMP-13表达水平与阴性对照组比较,差异无统计学意义(P>0.05)。结论钴铬合金和镍铬合金MKMP-13表达水平较高,一定程度上会损伤牙龈成纤维细胞;金、纯钛合金生物相容性比较好。

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Induction of tissue inhibitor of matrix metalloproteinase-2 by cholesterol depletion leads to the conversion of proMMP-2 into active MMP-2 in human dermal fibroblasts.

    Science.gov (United States)

    Kim, Sangmin; Oh, Jang-Hee; Lee, Youngae; Lee, Jeongyoon; Cho, Kwang Hyun; Chung, Jin Ho

    2010-01-31

    Cholesterol is one of major components of cell membrane and plays a role in vesicular trafficking and cellular signaling. We investigated the effects of cholesterol on matrix metalloproteinase-2 (MMP-2) activation in human dermal fibroblasts. We found that tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression and active form MMP-2 (64 kD) were dose-dependently increased by methyl-beta-cyclodextrin (MbetaCD), a cholesterol depletion agent. In contrast, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation were suppressed by cholesterol repletion. Then we investigated the regulatory mechanism of TIMP-2 expression by cholesterol depletion. We found that the phosphorylation of JNK as well as ERK was significantly increased by cholesterol depletion. Moreover, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation was significantly decreased by MEK inhibitor U0126, and JNK inhibitor SP600125, respectively. While a low dose of recombinant TIMP-2 (100 ng/ml) increased the level of active MMP-2 (64 kD), the high dose of TIMP-2 (>or=200 ng/ml) decreased the level of active MMP-2 (64 kD). Taken together, we suggest that the induction of TIMP-2 by cholesterol depletion leads to the conversion of proMMP-2 (72 kD) into active MMP-2 (64 kD) in human dermal fibroblasts.

  4. 基质金属蛋白酶2和基质金属蛋白酶9、血管内皮生长因子在非小细胞肺癌中的表达及临床意义%Expression and clinic pathological features of MMP 2, MMP 9 and VEGF in non - small - cell lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    李海燕; 郑有光; 程维刚; 陈丽萍; 张娜丽

    2011-01-01

    目的 观察非小细胞肺癌( NSCLC)标本中基质金属蛋白酶2(MMP 2)和MMP 9及血管内皮生长因子(VEGF)的表达,以探讨其在NSCLC中表达的意义,为临床的诊断、治疗和预后的判断提供参考.方法 用SP免疫组化技术检测MMP 2、MMP 9、VEGF在77例肺癌组织中的表达.结果 肺癌组织中MMP 2、MMP 9主要表达于肿瘤细胞的胞浆,在癌旁交界区组织也有表达,肿瘤组织的过表达率显著高于交界区(P<0.05),MMP 2、VEGF在肿瘤组织的过表达率与淋巴结转移状态、临床分期与原发肿瘤大小有关(P<0.05).结论 MMP 2、MMP 9、VEGF都参与了非小细胞癌发生、发展过程,MMP 2、VEGF在其中可能起到协同促进作用,MMP 2、VEGF联合分析可能更有助于评估NSCLC患者的预后.%Objective To investigate the expression and clinic pathological features of MMP2,MMP9 and VEGF in non - small - cell lung carcinoma,and provide reference for diagnosis,treatment and prognosis predictment of the disease.Methods MMP 2 and MMP 9,VEGF expressions were detected in 77 cases of non - small - cell lung carcinoma tissues and their adjacent tissues and 24 cases of normal lung tissues by steptavidinperoxdase immunohistochemical technique.Results The immunoreactivities of MMP 2 and MMP 9,VEGF were mainly shown in cytoplasma of tumor cells.The overexpressions of MMP 2 and MMP 9,VEGF in carcinoma tissues were significantly higher than in adjacent tissues ( P < 0.05).The overexpression of MMP 2 and VEGF in the cancer tissues were related to clinical stages,lymph node metastasis status and the size of primary cancer ( P < 0.05 ).There was a trend that the survival rate of these patients with overexpression of MMP 2 and MMP 9,VEGF was lower than that with non - overexpression,but there was no statistical significance.The survival rate of the group with both MMP 2 and MMP 9,VEGF overexpressions was lower than with non - overexpression ( P < 0.05 ).Conclusions MMP 2,MMP 9 and

  5. 类风湿性关节炎滑膜组织中PTTG1和MMP—2的表达及意义%Expression of PTTG-1 and MMP-2 and their biological significance in synoviun of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    王艳霞; 王瑞琳; 赵莉莉; 熊光宜; 徐瑾; 魏典; 李兰萍

    2012-01-01

    Purpose To detect the expression and distribution of PTTG1 and MMP-2 in synovial tissue of rheumatoid arthritis and to discuss their roles in the mechanism of rheumatoid arthritis. Methods SP immunohistochemical method was used to detect the expression of PTTG1 and MMP-2 in synovium of 68 rheumatoid arthritis cases and 14 osteoarthritis cases. Results The positive rates of PT-TG1 were 64. 7% in RA groups and 21. 4% in OA groups. The positive rates of MMP-2 were 73. 5% in RA groups and 28. 6% in OA groups. The expression of PTTG1 in RA group was significantly higher than that of OA group. The expression of MMP-2 in RA group was significantly higher than that of OA group. And there was correlation between PTTG1 and MMP-2. Conclusion The expression of both PTTG1 and MMP-2 increases in synovium of RA and there is significant correlation between them, which thereby suggests that they may have certain association in the pathogenesis of rheumatoid arthritis.%目的 检测类风湿性关节炎(rheumatoid arthritis,RA)患者滑膜被覆细胞及滑膜下组织中垂体肿瘤转化基因1(pituitary tumor transforming gene 1,PTTG1)及MMP-2的表达及分布状况,探讨其在RA发病中的作用.方法 采用免疫组化SP法检测68例RA患者,14例骨性关节炎(osteoarthritis,OA)患者滑膜被覆细胞及滑膜下组织中PTTG1及MMP-2的表达状况.结果 PTTG1在RA组、OA组阳性率分别为64.7%和21.4%;MMP-2在RA组、OA组阳性率分别为73.5%和28.6%,差异具有统计学意义(P<0.05),且PTTG1和MMP-2之间表达具有相关性(rs=0.776,P<0.05).结论 PTTG1和MMP-2在RA组滑膜组织的表达均明显升高,且二者之间的表达具有相关性,从而证实其在RA的发病机制中可能具有一定的作用.

  6. 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.

  7. 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.

  8. Expressão de MMP-2 e MMP-9 no endométrio de éguas saudáveis e portadoras de endometrite crônica

    Directory of Open Access Journals (Sweden)

    C.D Porto

    2011-02-01

    Full Text Available Avaliaram-se, por método imunoistoquímico, a expressão e distribuição das metaloproteinases (MMP 2 e 9 em amostras de endométrio hígido e de éguas portadoras de endometrite crônica. Foram utilizadas 60 biópsias endometriais. A MMP-2 foi observada na parede vascular, nas células estromais e no epitélio glandular, e a imunorreatividade mais intensa foi obtida nas células do epitélio glandular nas endometrites da categoria III e na parede vascular nos endométrios da categoria I. A marcação imunoistoquímica para MMP-9 mostrou-se difusa pelo endométrio e foi observada no epitélio luminal e glandular, na região da parede vascular, nas células estromais, endoteliais e do infiltrado inflamatório. Houve diminuição da marcação imunoistoquímica na região da parede vascular conforme aumentou o grau das lesões endometriais concomitante à diminuição da intensidade da reação. Não houve relação na expressão imunoistoquímica das metaloproteinases estudadas com o tipo de endometrite

  9. 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.

  10. 姜黄素对2型糖尿病神经病理性痛大鼠脊髓背角和背根神经节MMP-2及MMP-9表达的影响%Effect of curcumin on expression of MMP-2 and MMP-9 in spinal dorsal horn and dorsal root ganglion of rats with type 2 diabetic neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    吴绍胜; 孙传峰; 曹红; 李佳佳; 史小婷; 李军

    2014-01-01

    Objective To evaluate the effect of curcumin on the expression of MMP-2 and MMP-9 in the spinal dorsal horn and dorsal root ganglion (DRG) of rats with type 2 diabetic neuropathic pain (DNP).Methods Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin 35 mg/kg,and confirmed by fasting blood glucose level ≥ 16.7 mmol/L in male Sprague-Dawley rats.Type 2 DNP was confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdraw latency (TWL) measured on day 14 after streptozotocin administration < 80% of the baseline value.The rats were then randomly divided into 3 groups (n =27 each):type 2 DNP group (group DNP); curcumin group (group Cur); solvent control group (group SC).In Cur and SC groups,curcumin 100 mg/kg and corn oil 4 ml/kg were injected intraperitonally,respectively,once a day for 14 consecutive days starting from day 14 after streptozotocin administration.Another 27 normal Sprague-Dawley male rats served as control group (group C) and were fed with normal forage.MWT and TWL were measured before type 2 DNP was induced,after type 2 DNP was induced,and at 3,7 and 14 days after curcumin injection(T1-5).The rats were sacrificed after MWT and TWL were measured at T3-5,and the lumbar segments of the spinal cord and DRG (L4-6) were removed for determination of the expression of MMP-2 and MMP-9 by Western blot.Results Compared with group C,MWT was significantly decreased and TWL was shortened,and MMP-2 and MMP-9 expression in the spinal dorsal horn and DRG was up-regulated in DNP,Cur and SC groups.Compared with DNP group,MWT was significantly increased and TWL was prolonged,and MMP-2 and MMP-9 expression in the spinal dorsal horn and DRG was down-regulated in Cur group,and no significant changes were found in the parameters mentioned above in SC group.Conclusion The mechanism by which curcumin attenuates type 2 DNP may be related to up-regulation of the expression of MMP-2 and MMP-9 in the

  11. Characterization of porcine MMP-2 and its association with immune traits

    DEFF Research Database (Denmark)

    Huang, Honggang; Zhao, Weimin; Tang, Zhonglin;

    2009-01-01

    Matrix metalloproteinase-2 (MMP-2) plays important roles in inflammation and immunity besides its basic role in degrading and remodelling extracellular matrix (ECM). The expression of MMP-2 is up-regulated in many human as well as animal models of inflammatory and immune diseases. In this study, we...

  12. Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels

    NARCIS (Netherlands)

    Rutges, J. P. H. J.; Kummer, J. A.; Oner, F. C.; Verbout, A. J.; Roestenburg, H. J. A.; Dhert, W. J. A.; Creemers, L. B.

    2008-01-01

    Intervertebral disc (IVD) degeneration is associated with the increased expression of several matrix metalloproteinases (MMPs), in particular MMP-2. However, little is known about the actual activity of MMP-2 in healthy and degenerated discs, or what mechanisms are involved in its activation. A majo

  13. The Expressions of MMP-9,MMP-14,MMP-2 and VEGF-C in Breast Cancer and Their Significance%MMP-9、MMP-14、MMP-2和VEGF-C在乳腺癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    钱红; 曹桂明; 牛国梁; 杨梅; 黎晴

    2013-01-01

    [目的]探讨MMP-9、MMP-14、MMP-2和VEGF-C在乳腺癌中的表达及意义.[方法]用组织芯片和免疫组化技术检测乳腺良性病变及乳腺癌组织中MMP-2、MMP-9、MMP-14、VEGF-C的表达水平;用D2-40标记淋巴管并计数.[结果]MMP-9、MMP-14、MMP-2与VEGF-C在乳腺癌组织中的表达率及表达强度远高于乳腺良性病变组织,并呈正相关关系(r=-0.27、0.35、0.27、0.26);浸润性乳腺癌VEGF-C阳性表达率有淋巴结转移者明显高于无淋巴结转移者,差异有统计学意义(P<0.01).[结论] MMP-9、MMP-14、MMP-2与VEGF-C的表达与乳腺癌淋巴管生成及淋巴结转移关系密切并呈正相关.

  14. EXPRESS AND ROLE OF MATRIX METALLOPROTEINASE-2 (MMP-2)、 TISSUE INHIBITOR OF METALLOPROTEINASE-2 (TIMP-2)、 MEMBRANE TYPE 1-MATRIX METALLOPROTEINASE (MT1-MMP) mRNA IN AMELOBLASTOMA%成釉细胞瘤MMP-2、TIMP-2、MT1-MMP mRNA的表达和意义

    Institute of Scientific and Technical Information of China (English)

    张彬; 黄洪章; 潘朝斌; 陶谦

    2003-01-01

    目的探讨MMP-2、TIMP-2、MT1-MMP与成釉细胞瘤局部侵袭特性的生物学关系.方法采用RT-PCR方法检测基质金属蛋白酶及其抑制剂和激活剂MMP-2、TIMP-2、MT1-MMP在成釉细胞瘤的表达及含量.结果在成釉细胞瘤组织中,MMP-2、MT1-MMP、TIMP-2的mRNA均表达,且表达水平均显著高于正常牙囊组织,复发及实性成釉细胞瘤的TIMP-2、MT1-MMP相对含量均显著高于原发和囊性成釉细胞瘤.结论在成釉细胞瘤组织中,MMP-2、MT1-MMP、TIMP-2转录水平的增高可能与其侵袭特性有关,MT1-MMP/TIMP-2表达水平可能与其侵袭能力有关.

  15. Expression and clinical significance of MMP-2, MMP-7 and MMP-14 in the tissue of patients with gastric cancer%MMP-2、MMP-7和MMP-14在胃癌患者组织中表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    王一波; 汤黎明

    2015-01-01

    目的 探讨胃癌组织中MMP-2、MMP-7和MMP-14的表达及临床意义.方法 应用链霉素抗生物素蛋白-过氧化酶免疫组化染色法(S-P)法检测98例胃癌组织中MMP-2、MMP-7和MMP-14蛋白的表达.对照组20例为良性胃病变黏膜组织.结果 胃癌组中MMP-2、MMP-7和MMP-14表达的阳性率明显高于对照组(P<0.05);胃癌组中MMP-2及MMP-14的阳性表达率与胃癌的肿瘤浸润深度、淋巴转移、肿瘤大小、大体分型、临床肿瘤分期有关(P <0.05或P<0.01).MMP-7的阳性表达率与胃癌的肿瘤浸润深度、淋巴转移、分化程度、大体分型、临床肿瘤分期有关(P <0.05或P<0.01).MMP-2和MMP-7蛋白表达正相关性(r=0.271,P<0.01):MMP-2和MMP-14蛋白表达正相关性(r=0.268,P=<0.01);MMP-7和MMP-14蛋白表达正相关性(r =0.202,P<0.05).结论 MMP-2、MMP-7、MMP-14的表达上调与胃癌的浸润和转移有关.

  16. Expressão dos fatores VEGF, MMP-2 e 9, TIMP-1 e 2 no câncer de mama : correlação com o linfonodo sentinela e parâmetros clinicopatológicos

    OpenAIRE

    Flávio Cabreira Jobim

    2008-01-01

    Objetivo: Analisar a expressão dos fatores angiogênicos (VEGF, MMP-2 e MMP-9), e dos inibidores teciduais específicos de metaloproteinases da matriz (TIMP-1 e TIMP-2) em amostras de tumores, obtidas de um grupo de pacientes com câncer primário de mama, e avaliar a correlação destes com o linfonodo sentinela (LNS) e outros fatores clinicopatológicos selecionados, como idade, diâmetro do tumor, tipo histológico, grau histológico e invasão vascular. Métodos: Amostras de tumores primários, de 88 ...

  17. MMP2 — EDRN Public Portal

    Science.gov (United States)

    MMP2 is a member of the matrix metalloproteinase (MMP) family and is involved in many functions, such as remodeling of the vasculature, angiogenesis, tissue repair and remodeling, tumor invasion, inflammation, atherosclerotic plaque rupture, reproduction and embryonic development, as well as in disease processes such as arthritis and metastasis. In addition to degrading extracellular matrix proteins, MMP2 can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction and appears to have a role in myocardial cell death pathways. MMPs are generally secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The MMP2 protein degrades gelatin type I and collagen types IV, V, VII, and X. MMP2 gene mutations have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. There are two known isoforms of this gene, encoded by two transcript variants.

  18. Expression of matrix metalloproteinase 2 and 9 in hypertension-induced intracranial aneurysm in rats%实验性大鼠脑动脉瘤形成过程中MMP-2MMP-9表达的动态变化

    Institute of Scientific and Technical Information of China (English)

    马良; 付强; 关俊宏

    2013-01-01

    目的 探讨实验性大鼠动脉瘤形成过程中基质金属蛋白酶2 (MMP-2)、基质金属蛋白酶9(MMP-9)的表达规律.方法 制作肾性高血压大鼠脑动脉瘤模型,通过免疫组化在蛋白水平系统动态观察肾性高血压大鼠脑动脉瘤形成过程中MMP-2、MMP-9表达的变化.结果 实验组在术后1 w脑动脉壁即可见MMP-2、MMP-9表达增加,随着术后时间的推移和大鼠血压的增高,其表达也迅速增加,术后1个月基本达最高峰并一直持续至4个月,其中MMP-9较正常状态的增加比MMP-2的表达增加更为显著.对照组脑动脉壁MMP-2、MMP-9也有微弱表达,且MMP-2表达较MMP-9略强.结论 脑动脉壁MMP-9、MMP-2特别是MMP-9的过度表达导致的脑动脉壁胶原纤维及内弹力层破坏是脑动脉瘤形成的主要原因之一.%Objective To investigate the expression pattern of matrix metalloproteinase-2 (MVP-2),matnx metalloproteinase-9 (MMP-9) in the process of aneurysm formation in rats.Methods A rat model of cerebral aneurysm was established.The dynamic changes of MMP-2 and MMP-9 expressions were examined by irrmmunohistochemistry at the level of protein activity in the process of aneurysm formation.Results In experimental group,with the development of hypertension,the expressions of MMP-2 and MMP-9 were increased one week after operation,peaked at first month and lasted until 4 months after operation.The expression of MMP-9 was increased more remarkably than that of MMP-2.Weak staining of MMP-2 and MMP-9 was observed in the cerebral artery,and the expression of MMP-2 was little higher than that of MMP-9.Conclusion The over-expressions of MMP-2 and MMP-9 in artery which result in the wall destruction of collagen and internal elastic lamina of cerebral artery are the main cause of the aneurysm formation.

  19. Ki-67、MMP-7、MMP-2在宫颈CIN和宫颈癌中的表达及意义%Expression and significance of Ki-67, MMP-2 and MMP-7 in CIN and cervical cancer

    Institute of Scientific and Technical Information of China (English)

    滕燕伊; 刘晓云; 郑洪; 伍小智

    2010-01-01

    目的:检测Ki-67、MMP-7、MMP-2在宫颈CIN及宫颈癌中的表达情况,探讨Ki-67、MMP-7、MMP-2与宫颈癌的发生、发展,增殖和侵袭转移之间的关系.方法:采用免疫组化S-P法和图像分析技术检测Ki-67、MMP-7、MMP-2在已确诊的50例宫颈癌(Invasive cervical cancer,ICC)、23例宫颈上皮内瘤样变(Cervical intraepithelial neoplasm,CIN)和正常官颈(Normal cervical epithelium,NCE)对照20例的表达情况.结果:50例宫颈癌中ki-67、MMP-7、MMP-2的阳性表达分别为72.00%、78.00%、76.00%;CIN组ki-67、MMP-7、MMP-2的阳性表达分别为47.83%、60.87%、56.52%;正常对照组ki-67、MMP-7、MMP-2的阳性表达分别为10、0、0;Ki-67在子宫颈癌组和CIN组明显高于正常官颈上皮组,在腺癌中的表达高于鳞癌(P<0.05),在CIN Ⅰ和CIN Ⅱ、CIN Ⅲ中表达无明显差异,在低分化癌的表达明显高于高分化癌(P<0.05),在淋巴结转移组中的表达明显高于非淋巴结转移组(P<0.05);MMP-7、MMP-2在宫颈癌组织中的表达水平高于CIN及正常宫颈组织(P<0.01),MMP-7、MMP-2的表达与宫颈癌的病理类型及分化无关,在淋巴结转移组中表达高于非淋巴转移组.结论:Ki-67、MMP-2、MMP-7与宫颈癌肿瘤细胞的侵袭转移行为相关.

  20. Skin wound healing in MMP2-deficient and MMP2 / plasminogen double-deficient mice

    DEFF Research Database (Denmark)

    Frøssing, Signe; Rønø, Birgitte; Hald, Andreas;

    2010-01-01

    -sensitive MMPs during wound healing. To address whether MMP2 is accountable for the galardin-induced healing deficiency in wildtype and Plg-deficient mice, incisional skin wounds were generated in MMP2 single-deficient mice and in MMP2/Plg double-deficient mice and followed until healed. Alternatively, tissue...... was isolated 7 days post wounding for histological and biochemical analyses. No difference was found in the time from wounding to overt gross restoration of the epidermal surface between MMP2-deficient and wildtype control littermate mice. MMP2/Plg double-deficient mice were viable and fertile, and displayed...... an unchallenged general phenotype resembling that of Plg-deficient mice, including development of rectal prolapses. MMP2/Plg double-deficient mice displayed a slight increase in the wound length throughout the healing period compared with Plg-deficient mice. However, the overall time to complete healing...

  1. The expression and clinical signiifcance of Galectin­3 and MMP­2, TIMP­2 in human colorectal carcinoma%大肠癌组织中Galectin-3与MMP-2、TIMP-2的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    李英健; 赵恩宏; 苏锐; 侯雷; 刘志满; 申兴斌

    2014-01-01

    ObjectiveTo study the expression of Galectin-3 and MMP-2, TIMP-2 in colorectal carcinoma, and to investigate its in colorectal cancer progression of meaning in the course.MethodTo detect the expression of Galectin-3 and MMP-2,TIMP-2 in 52 cases of colorectal cancer, 20 cases of colorectal adenoma and 20 cases of colorectal normal mucosa tissue through the application of immunohistochemistry. Analyzed the relationship between its expression with the patient’s sex, age, tumor location, tumor differentiation, inifltration and lymph node metastasi.Result ①In colorectal carcinoma, the expression of Galectin-3 and MMP-2 were highest and the expression of TIMP-2 was lowest;②In inifltration over the muscle layer of the colorectal carcinoma and in poorly differentiated colorectal carcinoma and in lymph node metastasis of colorectal cancer tissues, the expression of Galectin-3 and MMP-2 were higher and the expression of TIMP-2 was lower;③The expression of Galectin-3 and MMP-2 were positive correlation and the expression of Galectin-3 and TIMP-2 were negative correlation in colorectal carcinoma.ConclusionThe imbalance expression of Galectin-3, MMP-2 and TIMP-2 is positive corrrelated with the invasion and metastasis of colorectal carcinoma.%目的:研究半乳糖凝集素-3(Galectin-3)与基质金属蛋白酶-2(MMP-2)、组织基质金属蛋白酶抑制剂-2(TIMP-2)在大肠癌中的表达,并探讨其在大肠癌进展过程中的意义。方法应用免疫组化法检测52例大肠癌组织、20例大肠腺瘤和20例大肠正常黏膜组织中Galectin-3与MMP-2、TIMP-2的表达情况。结果①Galectin-3、MMP-2在大肠癌中的阳性表达率最高,而TIMP-2在大肠癌中的阳性表达率最低;②大肠癌组织中,浸润程度深、低分化及有淋巴结转移的Galectin-3、MMP-2的表达明显升高,而TIMP-2的表达则明显降低;③在大肠癌组织中Galectin-3与MMP-2的表达呈正相关,而与TIMP-2的

  2. Niflumic acid exhibits anti-tumor activity in nasopharyngeal carcinoma cells through affecting the expression of ERK1/2 and the activity of MMP2 and MMP9.

    Science.gov (United States)

    Luo, Shengqun; Huang, Guoliang; Wang, Ziyou; Wan, Zheng; Chen, Hua; Liao, Dan; Chen, Chuyan; Li, Huahui; Li, Binbin; Chen, Liyong; Huang, Zunnan; He, Zhiwei

    2015-01-01

    Niflumic acid (NFA) was known to inhibit cell proliferation or migration in several types of cancer. However, the function of NFA in human nasopharyngeal carcinoma (NPC) cells was not clarified. The proliferation of NPC cell line CNE-2Z cells with NFA treatment was detected using the cell counting kit-8 method and transwell assay was employed to assess the effect of NFA on the CNE-2Z cell migration and invasion. The activity of MMP2 and MMP9 was detected by Gelatin Zymography. Cell cycle distribution and apoptosis were detected using flow cytometry. In vitro pull-down assay, western blot, and computational technique were applied to investigate the NFA regulating signaling pathway. Our results indicated that the growth capacity and colony formation potential of CNE-2Z cells in soft agar were significantly suppressed by treatment with NFA. NFA inhibited the proliferation of CNE-2Z cells in a concentration and time-dependent manner. NFA exerted an S phase arrest on the CNE-2Z cells in a concentration-dependent manner, while promoting apoptosis in a dose-dependent manner. Migration and invasion potential of CNE-2Z cells were decreased by NFA treatment in vitro. In vitro pull-down assay and molecular modeling indicated that NFA directly bound with early respond kinase 1 (ERK1). Finally, the anti-tumor effect of NFA was suggested to be mediated by inhibiting early respond kinases (ERK) expression and the MMP2 and MMP9 activities. NFA has proliferation-inhibiting, invasion-suppressing, cell cycle-blocking and apoptosis-promoting effects on CNE-2Z cells through regulation of ERK/MAPK and our results indicates that NFA may serve as a candidate of anticancer drug for NPC.

  3. MMP-2 is localized to the mitochondria-associated membrane of the heart.

    Science.gov (United States)

    Hughes, Bryan G; Fan, Xiaohu; Cho, Woo Jung; Schulz, Richard

    2014-03-01

    Matrix metalloproteinase-2 (MMP-2) has been extensively studied in the context of extracellular matrix remodeling but is also localized within cells and can be activated by prooxidants to proteolyze specific intercellular targets. Although there are reports of MMP-2 in mitochondria, a critical source of cellular oxidative stress, these studies did not take into account the presence within their preparations of the mitochondria-associated membrane (MAM), a subdomain of the endoplasmic reticulum (ER). We hypothesized that MMP-2 is situated in the MAM and therefore investigated its subcellular distribution between mitochondria and the MAM. Immunogold electron microscopy revealed MMP-2 localized in mitochondria of heart sections from mice. In contrast, immunofluorescence analysis of an MMP-2:HaloTag fusion protein expressed in HL-1 cardiomyocytes showed an ER-like distribution, with greater colocalization with an ER marker (protein disulfide isomerase) relative to the mitochondrial marker, MitoTracker red. Although MMP-2 protein and enzymatic activity were present in crude mitochondrial fractions, once these were separated into purified mitochondria and MAM, MMP-2 was principally associated with the latter. Thus, although mitochondria may contain minimal levels of MMP-2, the majority of MMP-2 previously identified as "mitochondrial" is in fact associated with the MAM. We also found that calreticulin, an ER- and MAM-resident Ca(2+) handling protein and chaperone, could be proteolyzed by MMP-2 in vitro. MAM-localized MMP-2 could therefore potentially impact mitochondrial function by affecting ER-mitochondrial Ca(2+) signaling via its proteolysis of calreticulin.

  4. Expressions of MMP-2 and TIMP-2 in lipopolysaccharide-induced acute lung injury of neonatal rats%MMP-2和TIMP-2在脂多糖诱导的新生大鼠急性肺损伤中表达的变化

    Institute of Scientific and Technical Information of China (English)

    殷静; 杨莉

    2009-01-01

    目的 探讨基质金属蛋白酶-2(matrix metallo proteinase-2,MMP-2)及其组织抑制剂(tissue inhibitors of metallo proteinase-2,TIMP-2)在脂多糖(LPS)诱导的新生大鼠急性肺损伤中的作用.方法 选择30只新生7日龄SD大鼠,随机分为生理盐水对照组(n=6)和急性肺损伤组(n=24),后者进一步分为1、2、4及6h亚组,每组6只.以LPS 腹腔注射建立急性肺损伤模型,观察注射LPS后不同时间点大鼠肺组织的病理改变,用免疫组织化学法和逆转录-聚合酶链反应(RT-PCR)法检测大鼠肺组织中MMP-2和TIMP-2的蛋白及mRNA表达.结果 病理学检查证实新生大鼠急性肺损伤模型复制成功.与生理盐水对照组比较,急性肺损伤组注射LPS后MMP-2蛋白及mRNA均表达增加,4~6h达高峰,差异有统计学意义(均P0.05).结论 LPS致新生大鼠的急性肺损伤存在MMP-2和TIMP-2的表达失衡,进而可能通过破坏基底膜参与急性肺损伤的病理过程.

  5. 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.

  6. Effects of Recombinant Human Leukemia Inhibitory Factor on the Expression of MMP-2, MMP-9 and TIMP-1 in the Trophoblastic Cells of Early Pregnancy%白血病抑制因子对人早孕滋养细胞MMP-2、MMP-9和TIMP-1表达的调节

    Institute of Scientific and Technical Information of China (English)

    宋恩学; 张炜; 刘银坤; 周剑萍; 杜国平

    2007-01-01

    目的:研究白血病抑制因子(LIF)对人早孕滋养细胞基质金属蛋白酶(MMP-2、MMP-9)和MMPs组织抑制物(TIMP-1)表达的影响.方法:以不同浓度的LIF作用于体外培养的细胞滋养细胞,于2 h、4 h、12 h收集细胞.用RT-PCR方法检测MMP-2、MMP-9和TIMP-1 mRNA的表达.结果:LIF对人早孕滋养细胞MMP-2和TIMP-1 mRNA的表达无明显作用.LIF作用4 h和12 h,实验组MMP-9 mRNA明显上升(P<0.01),并呈明显剂量依赖关系.结论:LIF可以在一定的时间和剂量范围内促进滋养细胞MMP-9的表达.推测LIF可能通过节制性调节MMPs的表达,进而分解子宫内膜细胞外基质,介导滋养细胞的入侵.

  7. CD147、MMP-1、MMP-2、MMP-9、TIMP-1、TIMP-2在不同级别的脑胶质瘤中的表达及其意义%Expressions of CD147, MMP-1, MMP-2,MMP-9,TIMP-1, TIMP-2 in different grades gliomas patients

    Institute of Scientific and Technical Information of China (English)

    居红格; 蒋剑英; 沈淑萍; 耿虹

    2010-01-01

    目的 探讨CD147、MMP-1、MMP-2、MMP-9、TIMP-1、TIMP-2在胶质瘤中的表达及其相关性,方法采用免疫组织化学法对78例石蜡包埋的胶质瘤组织和12例正常脑组织进行标记和分析.结果 CD147、MMP-1、MMP-2、MMP-9、TIMP-1、TIMP-2的阳性率分别为62%、66%、64%、75%、59%、59%,采用Spearman进行相关性分析,他们与胶质瘤的恶性程度均呈正相关(rs=0.2671~0.5631,P<0.05),CD147与MMP-1、MMP-2和MMP-9呈正相关(rs=0.3481~0.4951,P<0.05).结论 CD147、MMPS、TIMPs可以作为临床判断胶质瘤预后的分子生物学标志.

  8. CD147 promotes melanoma progression through hypoxia-induced MMP2 activation.

    Science.gov (United States)

    Zeng, W; Su, J; Wu, L; Yang, D; Long, T; Li, D; Kuang, Y; Li, J; Qi, M; Zhang, J; Chen, X

    2014-01-01

    Hypoxia enhances MMP2 expression and the invasion and metastatic potential of melanoma cells. CD147 has been shown to induce MMP2 in multiple cancers. To investigate the role of CD147 in hypoxiainduced MMP2 activation, we performed immunohistochemistry (IHC) staining in 206 normal and melanoma tissue samples, and analyzed the correlation between HIF1α and CD147. ChIP (chromosome Immunoprecipitation) in melanoma cell lines supports that HIF1α directly binds to CD147 promoter. Moreover, we made a series of deletion mutants of CD147 promoter, and identified a conserved HIF1α binding site. Point mutation in this site significantly decreased CD147 response to hypoxia. Importantly, knocking down CD147 attenuates MMP2 response to hypoxia in melanoma cell lines. MMP2 could not be efficiently activated by hypoxia in CD147 depletion cells. ELISA data showed that MMP2 secretion was reduced in CD147 depletion cells than control under hypoxia condition. To verify the data from cell culture model, we performed in vivo mouse xenograft experiment. IHC staining showed reduced MMP2 level in CD147 depleted xenografts compared to the control group, with the HIF1α level being comparable. Our study demonstrates a novel pathway mediated by CD147 to promote the MMP2 activation induced by hypoxia, and helps to understand the interplay between hypoxia and melanoma progression.

  9. 人牙髓中MMP-2与MMP-9受正畸力作用影响的初步分析%The expressions of MMP-2 and MMP-9 in human dental pulps under the effects of orthodontic Forces

    Institute of Scientific and Technical Information of China (English)

    赵莉琳; 刘鑫; 范小平; 向学熔

    2010-01-01

    目的:采用免疫组织化学方法,研究接受正畸力作用影响的人牙髓中MMP-2和MMP-9的表达.方法:选取接受正畸治疗的患者10名,于正畸治疗前确定应拔除的正畸牙,对其一侧选用常规正畸加力,另一侧健康同名牙不施加任何正畸力,作为同源对照,加力1d后至7d内拔除该正畸牙,各20颗,共40颗,分为加力组和对照组;选取临床诊断有牙髓炎症且无保留价值的第3磨牙20例,分为炎症组;对标本进行处理后制成切片,采用SP法,对其中MMP-2和MMP-9的表达进行图像分析和半定量分析.结果:对照组、加力组和炎症组牙髓均可见MMP-2和MMP-9的表达;在接受正畸力的牙髓组织,成牙本质细胞和牙髓成纤维细胞可见MMP-2和MMP-9表达,加力组牙髓中两者为表达增强,并且其表达强于同源对照正常的牙髓,但弱于炎症牙髓,三组差异具有统计学意义(P<0.05).结论:MMP-2和MMP-9在人牙髓中主要表达于成牙本质细胞和牙髓成纤维细胞的胞质中;生理条件下两者的水平较低,在接受正畸治疗时,由于受正畸力影响,牙髓处于应激状态,两者表达增强,应引起口腔医师的高度重视.

  10. 尿液中MMP-2、MMP-9及MMP-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-9及MMP-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-9及MMP-9/NGAL复合物的表达情况.结果 MMP-2、MMP-9、MMP-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-9和MMP-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-9、MMP-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.

  11. Imagerie moleculaire de la MMP-2

    Science.gov (United States)

    Lebel, Rejean

    MMPs (matrix metalloproteinases) are enzymes involved in tissue architecture remodelling and cell migration. MMP-2, particularly, was found to be a biomarker of the progression or prognosis of several pathologies, such as arthritis, atherosclerosis, infarct and cancer. Yet, its exact role in these pathologies is still uncertain. For these reasons, it is critical to develop new tools to enable the specific and non invasive study of MMP-2. As of now, a large number of optical probes (optical imaging), contrast agents (magnetic resonance imaging) and radiotracers (positron emission tomography, single photon emission tomography) have been published in the literature. However, none of the molecules allows for the specific quantification of MMP-2, particularly against MMP-9 which cleaves similar substrates. This thesis describes our progress in the development of new molecules capable of targeting and allowing the imaging of MMP-2. All tested molecules were fond to be quickly activated by MMP-2 and to be selective when compared with MMP3, MMP-7 and MMP-9. First, a contrast agent named PCA2-switch is tested in a mouse subcutaneous tumor model, and allows us to differentiate between tumors with low or high levels of MMP-2 activity. We also developed a panel of activatable fluorescent probes, one of which was found to be highly specific to MMP-2 (low activation by MMP9, efficient quenching). However, an extensive set of control experiments does not enable to conclude on the specificity of the probes in vivo. One of the principal limitations of many studies in the field of MMP imaging is the lack of proper controls, including unspecific uptake controls. The last section of this thesis discusses the impact of the EPR (enhanced permeability and retention) effect on the uptake of a non-specific probe in a subcutaneous tumor model treated with radiotherapy. Proper control experiments that should be performed when testing new MMP-2 probes are discussed. Keywords: Matrix

  12. Relationship of Matrix Metalloproteinase-2 and-9 Expression to Gastric Carcinoma Invasion and Metastasis%MMP-2、MMP-9与胃癌侵袭、转移的关系

    Institute of Scientific and Technical Information of China (English)

    钟华; 廖爱军; 刘迪群

    2012-01-01

    目的 探讨MMP-2、MMP-9的表达与胃癌侵袭和转移的关系.方法 采用免疫组化方法检测44例胃癌患者胃黏膜标本中MMP-2、MMP-9的表达情况.结果 有浆膜浸润的胃癌患者其MMP-2、MMP-9的阳性表达率均显著高于无浆膜浸润的胃癌患者(均P<0.01),有淋巴结转移的胃癌患者其MMP-2、MMP-9的阳性表达率均显著高于无淋巴结转移的胃癌患者(均P<0.01).结论 MMP-2、MMP-9表达与胃癌侵袭、转移有关,其表达增加提示胃癌有较高的恶性生物学行为.MMP-2、MMP-9可能成为评价胃癌恶性生物学特性的指标.

  13. 子宫颈鳞癌中MMP-2,MMP-9的表达及意义%Expression of Matrix Metalloproteinase in Cervical Squamous Cell Carcinoma and Its Significance

    Institute of Scientific and Technical Information of China (English)

    林蓓; 蔡威; 张淑兰

    2003-01-01

    目的: 探讨基质金属蛋白酶(MMP-2,MMP-9)与宫颈鳞癌的发生、发展及侵袭的关系.方法: 32例宫颈鳞状细胞癌为实验组,慢性宫颈炎及正常宫颈组织各30例为对照组.明胶酶谱法测定活性型MMP-2及MMP-9蛋白的含量,RT-PCR技术检测MMP-2及MMP-9 mRNA表达水平.结果:宫颈鳞癌组织中MMP-2及MMP-9酶活性和MMP-2及MMP-9 mRNA表达量均显著高于慢性宫颈炎及正常宫颈组织(P均<0.01).结论: MMP-2及MMP-9与宫颈鳞癌的发生、发展及侵袭有关.

  14. 茄碱通过调控Stat3信号通路影响胰腺癌细胞Panc-1中MMP-2和MMP-9表达%Solanine effects the expression of MMP-2 and MMP-9 in PANC-1 by regulating Stat3 pathway

    Institute of Scientific and Technical Information of China (English)

    吴素娜; 刘乐伟; 黄智铭

    2016-01-01

    目的 探讨茄碱对胰腺癌细胞Panc-1中基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)表达的影响及Stat3信号通路在此过程中的作用.方法 实验分为对照组和药物组,药物组分别采用浓度为3.5、7.0和10.5 μmol/L的茄碱对Panc-1细胞进行干预,明胶酶谱法观察茄碱对细胞中MMP-2和MMP-9活性的影响;实时荧光定量PCR检测MMP-2和MMP-9基因的表达变化;Western blotting法检测总蛋白中信号转导及转录激活因子3 (Stat3)蛋白的磷酸化表达变化.结果 与对照组相比,药物组(7.0、10.5 μmol/L)MMP-2活性明显下降(t值分别为2.4、6.4,P<0.05);MMP-9活性亦下降(t值分别为3.2、4.8,P< 0.05).实时荧光定量PCR结果显示,药物组(7.0μmol/L、10.5 μnol/L)MMP-2基因表达下调(t值分别为8.7、13,P< 0.05);MMP-9基因表达下调(t值分别为3.2、16.3,P< 0.05).Western blotting结果显示,随着茄碱浓度的增加,Panc-1细胞中Stat3蛋白磷酸化受到明显抑制(t值分别为10.2、6.4、6.2,P< 0.05),延长药物处理的时间(12 h、18 h、24 h)亦可抑制Stat3蛋白磷酸化(t值分别为11.4、26.1、20.4,P< 0.05).结论 茄碱可抑制胰腺癌细胞Panc-1中MMP-2和MMP-9的表达,发挥其抗肿瘤转移能力.其具体机制可能与调控Sata3信号通路有关.

  15. The expression of MMP-2,INF-r and CRP in seram in patients with coronary heart disease who helicobacter pylori positive%MMP-2、INF-r及超敏CRP在HP阳性的CHD患者血清中的表达

    Institute of Scientific and Technical Information of China (English)

    王淑华

    2015-01-01

    Objective:Investigate influence of Helicobacter pylori(HP) infection on MMP-2 and INF-r and hypersensitivity CRP(hsCRP) in serum in patients with Coronary heart disease (CHD) and, study relationship of CHD and HP infection and, to explore a new good method for treating and guarding against CHD more early. Methods:One hundred case of inpatients were from January 2012 to March 2014 Heze Municipal Hospital Cardiology diagnosed as AMI according to analyze retrospectively, ECG and Coronary angiograply and combined with clinical history .and also select no signs of CHD 100 case of healthy control group .For each group , measured ELLSA HP-CagA-IgG test to compare each group positive rate of HP infection. Then the above test were HP positive CHD patients that divided into HP severe infection CHD group and HP mild infection CHD group .and the HP-negative healthy group without signs of CHD as negative HP infection control group . For three groups detected MMP-2 and INF-r and HsCRP by ELLSA Roche automated microplate reader and specific protein analyzer.Test results were analyzed in each group ,compared teach group and the control group and the difference between the HP severe infection CHD group and HP mild infection CHD group.Results:First, HP-CagA-IgG test positive rate:CHD group 70.1%, significantly higher than those without CHD signs of healthy control group 44.6%, with statistic significance (P<0.001). Second , HP severe infection CHD group:MMP-2(373±126)ug/L and INF-r(385±128) ug/L and hsCRP(97.38±26.7);HP mild infection CHD group:MMP-2(237±139)ug/L and INF-r(276±134)ug/L and超敏CRP(56.19±17.4)ug/L were significantly higher than negative HP infection control group:MMP-2(142±72)ug/L and INF-r(135 ± 67)ug/L and (4.75±3.71),there were significant difference P<0.001);Significant difference (P<0.01) was showed between HP severe infection CHD group and HP mild infection CHD group. Conclusions:HP infection may be through the infiltration of inflammatory cells

  16. 麝香乌龙丸对大鼠佐剂性关节炎滑膜病变及HIF-1α、MMP-2表达水平的影响%Influence of Shexiang Wulong Pill on the Pathological Changes of Synovium in Adjuvant Arthritis and the Expression of HIF-1αand MMP-2 in Rats

    Institute of Scientific and Technical Information of China (English)

    孟凡双; 王志文; 仲伟静; 赵艳梅; 张娟; 丁春菊; 李臣杰; 向南; 李怡良

    2016-01-01

    目的:观察麝香乌龙丸对大鼠佐剂性关节炎(RA)滑膜病理形态及缺氧诱导因子-1α(HIF-1α)、基质金属蛋白酶-2(MMP-2)表达水平的影响.方法:将60只健康雄性wistar大鼠,随机抽取12只为对照组,其余48只造模成功后分为模型组、麝香乌龙丸低剂量组、麝香乌龙丸中剂量组、麝香乌龙丸高剂量组,每组各12只.麝香乌龙丸低剂量组、麝香乌龙丸中剂量组、麝香乌龙丸高剂量组分别灌入麝香乌龙丸0.3 g·(kg·d)-1、0.6 g· (kg· d)-1、1.2 g.(kg·d)-1,对照组、模型组灌入等容量生理盐水,连续2周.灌胃2周后,HE染色,光镜下观察滑膜病变,免采用疫组织化学法检测滑膜组织HIF-1α、MMP-2表达水平.结果:麝香乌龙丸能减轻RA大鼠滑膜病变的程度,各组大鼠滑膜病理形态评分比较,差异具有统计学意义(P<0.05);麝香乌龙丸各组可不同程度的降低RA大鼠滑膜中HIF-1α、MMP-2的表达水平,与模型组比较,差异均有统计学意义(P<0.05).结论:麝香乌龙丸治疗RA的机理与调节HIF-1α、MMP-2的表达水平有关.

  17. Identification of MMP-2 as a novel enhancer of cerebellar granule cell proliferation.

    Science.gov (United States)

    Verslegers, Mieke; Van Hove, Inge; Buyens, Tom; Dekeyster, Eline; Knevels, Ellen; Moons, Lieve

    2013-11-01

    During the first postnatal days in the mouse, granule cells (GCs) undergo massive proliferation, which then gradually decreases. Matrix metalloproteinase-2 (MMP-2), a Zn(2+)-dependent proteolytic enzyme, is involved in a wide variety of pathological and physiological pathways. Evidence for a role of this proteinase in cell proliferation is emerging, reporting its involvement in pathological proliferation, as well as during neurogenesis and developmental proliferation of non-CNS tissues. In this study, MMP-2 protein expression was observed within the early postnatal cerebellar cortex, predominantly in Purkinje cells and within the GC proliferative zone, i.e. the superficial external granular layer (EGL). Consistently, the spatiotemporal MMP-2 mRNA and protein profiles highly correlated with the peak of GC precursor (GCP) proliferation and detailed morphometric analyses of MMP-2 deficient cerebella revealed a thinner EGL due to a decreased GCP proliferation. BrdU cumulative experiments, performed to measure the length of different cell cycle phases, further disclosed a transiently prolonged S-phase in MMP-2 deficient GCPs during early cerebellar development. In consequence, MMP-2 deficient animals displayed a transient delay in GC migration towards the IGL. In conclusion, our findings provide important evidence for a role for MMP-2 in neuronal proliferation and cell cycle kinetics in the developing CNS.

  18. The Expression and Significance of Matrix Metalloproteinase-2 and CD147 in Gastric Carcinoma%CD147及MMP-2在胃癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    黄悦; 赵建华; 樊克武

    2007-01-01

    目的 探讨CD147及基质金属蛋白酶-2(MMP-2)在胃癌中表达特点及其生物学行为关系.方法 应用免疫组织化学S-P法检测58例胃癌组织及20例正常胃黏膜组织中CD147和MMP-2的表达情况.结果 CD147及MMP-2在胃癌组中的阳性表达率分别为77.6%及82 8%,均高于正常胃黏膜组(P<0.01);两者的阳性表达均与胃癌的浸润深度、临床分期及淋巴结转移有关,与分化程度无明显关联;胃癌中CD147及MMP-2的表达具有相关性(P<0.01).结论 胃癌组织中CD147和MMP-2的高表达,可以作为胃癌生物学行为的客观参考指标.

  19. Rock2 promotes the invasion and metastasis of hepatocellular carcinoma by modifying MMP2 ubiquitination and degradation.

    Science.gov (United States)

    Huang, Da; Du, Xiaohong; Yuan, Rongfa; Chen, Leifeng; Liu, Tiande; Wen, Chongyu; Huang, Mingwen; Li, Ming; Hao, Liang; Shao, Jianghua

    2014-10-10

    Rho-associated coiled-coil-containing protein kinase 2 (Rock2) is a downstream effector of Rho that plays an important role in the tumorigenesis and progression of hepatocellular carcinoma (HCC). Matrix metalloproteinase 2 (MMP2) is a master regulator of tumor metastasis. In this study, we investigated the collections of Rock2 and MMP2 in HCCs and determined the potential role and molecular mechanism of Rock2 in MMP2-mediated invasiveness and metastasis. We found that Rock2 and MMP2 were markedly overexpressed in HCCs compared with the corresponding adjacent tissues, where a positive correlation in their expression was found. The knockdown of Rock2 significantly decreased MMP2 expression and inhibited the invasion and metastasis of HCC in vitro and in vivo. Additionally, the upregulation of MMP2 rescued the decreased migration and invasion induced by the knockdown of Rock2, whereas the knockdown of MMP2 decreased Rock2-enhanced HCC migration and invasion. Mechanistically, Rock2 stabilized MMP2 by preventing its ubiquitination and degradation. Together, our results link two drivers of invasion and metastasis in HCC and identify a novel pathway for MMP2 control.

  20. Correlative studies of the expression of matrix metalloproteinase 2 and 9 in human bladder cancer%MMP-2和MMP-9在膀胱癌组织中的表达及相关性研究

    Institute of Scientific and Technical Information of China (English)

    陈国俊; 王健

    2007-01-01

    目的:研究MMP-2和MMP-9在膀胱移行细胞癌组织中的表达及其与膀胱癌侵袭、转移的关系.方法:应用链霉菌抗生物素蛋白-过氧化酶(S-P)免疫组化方法,检测5例正常膀胱组织和49例膀胱移行细胞癌组织中MMP-2和MMP-9的表达水平.结果:MMP-2、MMP-9在膀胱正常组织中均呈阴性表达,在49例膀胱癌组织中均不同程度的表达.随肿瘤分级的增高,MMP-2和MMP-9的表达显著增强(P值均小于0.05);随肿瘤分期的增高,MMP-2的表达也显著增强(P<0.05),而MMP-9在膀胱肿瘤低期和高期之间无显著性差异(P>0.05).结论:MMP-2、MMP-9与膀胱癌的侵袭转移有关,且MMP-2可能对判断膀胱癌的预后有帮助.

  1. The inhibition of calpains ameliorates vascular restenosis through MMP2/TGF-β1 pathway.

    Science.gov (United States)

    Tang, Lianghu; Pei, Haifeng; Yang, Yi; Wang, Xiong; Wang, Ting; Gao, Erhe; Li, De; Yang, Yongjian; Yang, Dachun

    2016-07-25

    Restenosis limits the efficacy of vascular percutaneous intervention, in which vascular smooth muscle cell (VSMC) proliferation and activation of inflammation are two primary causal factors. Calpains influence VSMC proliferation and collagen synthesis. However, the roles of calpastatin and calpains in vascular restenosis remain unclear. Here, restenosis was induced by ligating the left carotid artery, and VSMCs were pretreated with platelet-derived growth factor (PDGF)-BB. Adenovirus vector carrying MMP2 sequence and specific small interfering RNA against calpain-1/2 were introduced. Finally, restenosis enhanced the expression of calpain-1/2, but reduced calpastatin content. In calpastatin transgenic mice, lumen narrowing was attenuated gradually and peaked on days 14-21. Cell proliferation and migration as well as collagen synthesis were inhibited in transgenic mice, and expression of calpain-1/2 and MMP2/transforming growth factor-β1 (TGF-β1). Consistently, in VSMCs pretreated with PDGF-BB, calpastatin induction and calpains inhibition suppressed the proliferation and migration of VSMCs and collagen synthesis, and reduced expression of calpain-1/2 and MMP2/TGF-β1. Moreover, simvastatin improved restenosis indicators by suppressing the HIF-1α/calpains/MMP2/TGF-β1 pathway. However, MMP2 supplementation eliminated the vascular protection of calpastatin induction and simvastatin. Collectively, calpains inhibition plays crucial roles in vascular restenosis by preventing neointimal hyperplasia at the early stage via suppression of the MMP2/TGF-β1 pathway.

  2. Angiogenin contributes to bladder cancer tumorigenesis by DNMT3b-mediated MMP2 activation.

    Science.gov (United States)

    Peres, Rafael; Furuya, Hideki; Pagano, Ian; Shimizu, Yoshiko; Hokutan, Kanani; Rosser, Charles J

    2016-07-12

    Epigenetic-mediated gene activation/silencing plays a crucial role in human tumorigenesis. Eliciting the underlying mechanism behind certain epigenetic changes is essential for understanding tumor biology. Previous studies in human cancers revealed an unrecognized interplay between Angiogenin (ANG) and matrix metalloproteinase-2 (MMP2) leading to pronounced tumorigenesis. Here we provide multiple lines of evidence further indicating ANG oncogenic potential. ANG expression resulted in the hypomethylated state of the MMP2 gene, which led to increased gene expression of MMP2. More than that, our global DNA methylation microarray analysis showed that gene manipulation of ANG affected a variety of pathways, such as cell migration, angiogenesis and specifically, tumor suppressor genes. Mechanistically, ANG negatively regulated DNA methyltransferase 3b (DNMT3b) enzymatic activity by down-regulating its expression and inhibiting its recruitment to the MMP2 promoter. Consistent with this, ANG-MMP2 overexpression and DNMT3b underexpression correlated with reduction in disease free survival of human bladder cancer patients. Together, the results continue to establish ANG as an oncoprotein and further reveal that ANG contributes to oncogenesis by the activation of MMP2 through modulation of DNMT3b functions.

  3. Expression of Matrix Metalloproteinase-2 and -9 in Carcinoma of Esophagus%食管癌基质金属蛋白酶MMP-2和MMP-9表达的意义

    Institute of Scientific and Technical Information of China (English)

    王雪梅

    2005-01-01

    目的:探讨基质金属蛋白酶MMP-2和MMP-9在食管癌组织中的表达及其与食管癌浸润转移的关系.方法:用免疫组化S-P法分别检测59例食管癌组织中MMP-2和MMP-9的表达.结果:MMP-2和MMP-9阳性表达率食管腺癌分别为84.61%、76.92%,明显高于食管鳞癌50.00%、43.48%,P<0.05;淋巴结转移组分别为93.33%、86.67%,明显高于无淋巴结转移组41.38%、37.93%,P<0.01.结论:MMP-2和MMP-9在食管癌侵袭及转移过程中可能发挥重要作用.

  4. 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.

  5. Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2.

    Science.gov (United States)

    Xuan, Xaioyan; Li, Shanshan; Lou, Xi; Zheng, Xianzhao; Li, Yunyun; Wang, Feng; Gao, Yuan; Zhang, Hongyan; He, Hongliu; Zeng, Qingru

    2015-05-01

    Stat3 alters the expression of its downstream genes and is associated with tumor invasion and metastasis in several human cancers. Its role in esophageal squamous cell carcinoma (ESCC) has not been well characterized. We examined the tumor sections of 100 cases of ESCC by immunohistochemistry and observed significant overexpression of Stat3 in the cytoplasm of 89% of ESCC cells and of phosphorylated Stat3 (p-Stat3) in the nuclei of 71% of ESCC when compare with normal esophageal mucosa (72%, p = 0.02; and 31%, p = 0.001). Overexpression of Stat3 and p-Stat3 positively correlated with that of matrix metalloproteinase-2 (MMP2), a known regulator for cell migration, in 65% of ESCC while only 26% shown in benign esophageal mucosa. To further investigate the association of Stat3 with tumor metastasis in vitro, invasion of EC-1 cells (a human ESCC cell line) were investigated with Boyden chambers. The results showed that transfection of Stat3 not only promoted invasion of EC-1 cells but also significantly induced MMP2 expression in a dose-dependent manner. In contrast, suppressing expression of endogenous Stat3 mRNA and protein by Stat3 siRNA significantly reduced EC-1 cell invasion and MMP2 expression. A high-affinity Stat3-binding element was localized to the positions of 648-641 bp (TTCTCGAA) in the MMP2 promoter with electrophoretic mobility shift assay. Our results suggest that Stat3, p-Stat3, and MMP2 were overexpressed in ESCC and associated with invasion of ESCC; and Stat3 up-regulated expression of MMP2 in ESCC through directly binding to the MMP2 promoter.

  6. 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.

  7. MMP-2、MMP-9及其抑制因子TIMP-2、TIMP-1在非黑色素性皮肤癌中的表达及意义%Expressions and significances of MP-2, MMP-9, TIMP-2, TIMP-1 in skin basal cell carcinoma and squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    黄静仪; 刘林蟠; 张建文

    2011-01-01

    Objective To investigate the expressions and significances of matrix metalloproteinase-2 (MMP-2),matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2),tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) protein in skin basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods Twenty six patients with SCC and twenty two patients with BCC.confirmed by pathology.were selected. Immunohistochemistry of tissues were performed using SABC method. Expression rate.staining intensity and expression intensity of every factor were recorded. Meanwhile,20 normal skin was selected as control. The results were compared between the groups. Results Compared with control group, expression rate.staining intensity and expression intensity of MMP-2, MMP-9 in SCC and BCC groups were significantly higher,TIMP-2,TIMP-1 in SCC and BCC groups were significantly lower (P<0.05). Expression intensity of MMP-2.MMP-9 in SCC group were higher than those in BCC group, TIMP-2.TIMP-1 in SCC group were lower than those in BCC group(P<0.05). Conclusion MMP-2.MMP-9 and TIMP-2.TIMP-1 may play an important role in development, progression,invasion and metastasis of SCC and BCC.%目的:分析MMP-2、MMP-9及其抑制因子TIMP-2、TIMP-1在非黑色素性皮肤癌中的表达情况及临床意义.方法:选取病理证实的SCC患者26例(SCC组),BCC患者22例(BCC组).手术切除病变组织,采用SABC法行免疫组化检测,记录各因子表达阳性率、染色强度和表达强度.同时,取20例正常皮肤为对照组.比较SCC组、BCC组患者及对照组各因子表达情况差异.结果:SCC组和BCC组与对照组MMP-2、MMP-9相比,表达阳性率、染色强度和表达强度显著增高,SCC组和BCC组与对照组TIMP-2、TIMP-1的表达阳性率、染色强度和表达强度明显降低(P<0.05).SCC组MMP-2、MMP-9的表达强度显著高于和BCC组,而TIMP-1、TIMP-2表达强度显著低于BCC组(P<0.05).结论:MMP-2、MMP-9

  8. Effects of FuMing Tablets on Expression of MMP-2 in Retinal Tissue After Retinal Detachment of Rabbit%复明片对兔视网膜脱离后视网膜组织中基质金属蛋白酶-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘娉; 彭俊; 彭清华; 姚小磊

    2011-01-01

    Objective: To investigate the effects of FuMing Tablets (FMT) of qi - benefitting, yin - fostering, and blood - invigorating and diuresis - activating on the expression of MMP - 2 in the retinal tissue after detachment of the retina of rabbit. Methods: 36 rabbits were divided into normal contrast group (group A) , retinal detachment model group ( group B), western medicine contrast group ( group C) , FMT group( group D). Each group had 9 rabbits. Group B, C, D were made retinal detachment model. After models were made one day they were given medicine. Group A and B were administrated intragastrically with 5ml/kg warm water, once a day. Group C was administrated intragastrically with 5ml/ kg western medicine solution, once a day. Group D was administrated intragastrically with 5ml/kg FMT suspension, once a day. Then adopting the method s - p to investigate the expression of Matrix Metallo - proteinase - 2, MMP - 2 in the retinal tissue respectively in the 7th day, 14th day and 21st day. Results: MMP -2 takes on strong positive expression in the RPE ceils of model group and west medicine group, dyeing dark or pretty dark color; while weak masculine expression in the RPE cells of FMP group, dyeing shallow color. Conclusions: FMT with the functions of benefiting qi, nourishing yin, activating blood and draining water, can decrease the expression of MMP- 2 in the retinal tissue.%目的:研究益气养阴活血利水之复明片对兔实验性视网膜脱离后视网膜组织中MMP-2表达的影响.方法:将36只有色家免随机分为正常对照组(A组)、模型组(B组)、西药对照组(C组)、复明片组(D组),每组9只.B、C、D组制作视网膜脱离模型.造模后第1d下午开始给药,A组与B组均予温开水灌胃,5mL/kg体重,1次/d;C组予西药混合溶液灌胃,5ml/kg体重,1次/d;D组予复明片混悬液灌胃,5mL/kg体重,1次/d.并于造模后第7、14、21天采用S-P免疫组化法检测视网膜组织中基质金属蛋白酶-2(Matrix

  9. Matrix metalloproteinase (MMP)-2 gene polymorphisms affect circulating MMP-2 levels in patients with migraine with aura.

    Science.gov (United States)

    Gonçalves, Flavia M; Martins-Oliveira, Alisson; Lacchini, Riccardo; Belo, Vanessa A; Speciali, Jose G; Dach, Fabíola; Tanus-Santos, Jose E

    2013-01-01

    Matrix metalloproteinases (MMP) are involved in the disruption of blood-brain barrier (BBB) during migraine attacks. In the present study, we hypothesized that two functional polymorphisms (C(-1306)T and C(-735)T) in MMP-2 gene and MMP-2 haplotypes are associated with migraine and modify MMP-2 and tissue inhibitor of MMP (TIMP)-2 levels in migraine. Genotypes for MMP-2 polymorphisms were determined by real time-PCR using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by gelatin zymography and ELISA, respectively, in 148 healthy women without history of migraine and in 204 women with migraine (153 without aura; MWA, and 51 with aura; MA). Patients with MA had higher plasma MMP-2 concentrations and MMP-2/TIMP-2 ratios than patients with MWA and controls (P0.05), we found that the CC genotype for C(-735)T polymorphism and the CC haplotype were associated with higher plasma MMP-2 concentrations in MA group (P<0.05). Our findings may help to understand the role of MMP-2 and its genetic variants in the pathophysiology of migraine and to identify a particular group of migraine patients with increased MMP-2 levels that would benefit from the use of MMP inhibitors.

  10. MMPs/TIMPs系统在小鼠急性放射性肺损伤中的表达%Increased expressions of MMP-2 and MMP-9 in lung following 12 Gy local irradiation

    Institute of Scientific and Technical Information of China (English)

    杨坤禹; 刘莉; 张涛; 胡豫; Claudia Ruebe; Christian Ruebe; 伍钢

    2006-01-01

    目的 通过检测基质金属蛋白酶(MMPs)和基质金属蛋白酶组织抑制物(TIMPs)在单次大剂量胸部照射小鼠肺组织中的表达,探讨全肺照射诱导的MMPs/TIMPs系统表达紊乱在放射性肺损伤发生与发展中的作用.方法 实验组小鼠在出生后8周时给予单次胸部照射12 Gy,对照组小鼠给予假照射.在照射后4和8周时处死小鼠,收集肺组织标本,测定肺组织中MMP-2、MMP-9、MMP-3、MMP-13、TIMP-1、TIMP-2和TIMP-3蛋白的表达.结果 照射后4和8周时,实验组小鼠肺组织中MMP-2表达水平分别为对照组的1.7和1.9倍,MMP-9表达水平分别为对照组的2.7和2.6倍,而MMP-3、MMP-13、TIMP-1、TIMP-2、和TIMP-3的表达水平与对照组比较无显著改变.结论 辐射诱导小鼠肺组织中MMP-2和MMP-9的表达增加,可能加剧了急性放射性肺损伤.

  11. MMP-2 and MMP-9 Expression in Cerebral Ischemia and Research Progress of Acupuncture Regulation%MMP-2、MMP-9与脑缺血以及针刺调节作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    成越; 倪光夏

    2015-01-01

    Ischemic stroke is the leading cause of disability or death all over the world.The study finds that matrix metalloproteinase-2 ( MMP-2 ) and matrix metalloproteinase-9 ( MMP-9 ) play important roles in is-chemic brain injury.They involve in the destruction of the blood brain barrier, brain edema and hemorrhagic transformation process.Therefore, it is the key to inhibiting the activities of MMP-2 and MMP-9.The early intervention of acupuncture can inhibit the activities of MMP-2 and MMP-9 effectively, and it is safe and easy to operate.It is also economical.It may be a new way for the treatment of cerebral ischemia injury.The relationship between MMP-2 and MMP-9 and cerebral ischemia and the therapeutic effect of acupuncture are reviewed as follows.%缺血性脑卒中是全世界疾病中致残或致死的主要原因。研究发现基质金属蛋白酶-2( MMP-2)与基质金属蛋白酶-9(MMP-9)在缺血性脑损伤中发挥了重要的作用,其参与了血脑屏障的破坏、脑水肿及出血性转化等过程,因此抑制MMP-2、MMP-9成为治疗的关键。针刺早期介入治疗能够有效地抑制MMP-2、MMP-9,且具有安全、操作简便、经济等优点,是治疗脑缺血损伤的一种新途径。故本研究将MMP-2、MMP-9与脑缺血的关系以及针刺的治疗作用做以综述。

  12. 早期自然流产胎盘绒毛基质金属蛋白酶-2表达增强%Increased expression of MMP-2 in plancetal villi of early spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    王乾兴; 谭兵兵; 谭晓珊; 杨高巧; 张先平

    2006-01-01

    早期自然流产(early spontaneous abortion)是指妊娠12周内胚胎或胎儿在宫内停止发育而排出的病理性妊娠,发生率占全部自然流产的62%以上.胎盘形成过程中,滋养层细胞对子宫蜕膜的侵入及对子宫螺旋小动脉的“血管重铸”是胎盘建成的关键步骤.基质金属蛋白酶(matrix metalloprotein-ases,MMPs)是一组含有Zn2+能降解绝大多数细胞外基质(extracellular,ECM)的肽链内切酶.研究证实,MMP-2和9是恒河猴滋养层细胞侵入子宫内膜和胎盘形成的关键因子,但对人早期自然流产过程中的表达情况尚未见报道.本研究首次采用明胶酶谱法研究早期自然流产胎盘绒毛中MMP-2和9的活性变化,以探讨其与早期自然流产的关系。

  13. PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA, Rho A, and Ras with inhibition of MMP-2, -7 and -9 gene expression.

    Science.gov (United States)

    Chou, Yu-Cheng; Chang, Meng-Ya; Wang, Mei-Jen; Yu, Fu-Shun; Liu, Hsin-Chung; Harnod, Tomor; Hung, Chih-Huang; Lee, Hsu-Tung; Chung, Jing-Gung

    2015-11-01

    Glioblastoma is the most aggressive primary brain malignancy, and the efficacy of multimodality treatments remains unsatisfactory. Phenethyl isothiocyanate (PEITC), one member of the isothiocyanate family, was found to inhibit the migration and invasion of many types of human cancer cells. In our previous study, PEITC induced the apoptosis of human brain glioblastoma GBM 8401 cells through the extrinsic and intrinsic signaling pathways. In the present study, we first investigated the effects of PEITC on the migration and invasion of GBM 8401 cells. PEITC decreased the migration of GBM 8401 cells in a dose-dependent manner as determined from scratch wound healing and Transwell migration assays. The percentage of inhibition ranged from 46.89 to 15.75%, and from 27.80 to 7.31% after a 48-h treatment of PEITC as determined from the Transwell migration assay and invasion assay, respectively. The western blot analysis indicated that PEITC decreased the levels of proteins associated with migration and invasion, Ras, uPA, RhoA, GRB2, p-p38, p-JNK, p-ERK, p65, SOS1, MMP-2, MMP-9 and MMP-13, in a dose-dependent manner. Real-time PCR analyses revealed that PEITC reduced the mRNA levels of MMP-2, MMP-7, MMP-9 and RhoA in a dose- and time-dependent manner. PEITC exhibited potent anticancer activities through the inhibition of migration and invasion in the GBM 8401 cells. Our findings elucidate the possible molecular mechanisms and signaling pathways of the anti-metastatic effects of PEITC on human brain glioblastoma cells, and PEITC may be considered as a therapeutic agent.

  14. Gamma-linolenic acid inhibits both tumour cell cycle progression and angiogenesis in the orthotopic C6 glioma model through changes in VEGF, Flt1, ERK1/2, MMP2, cyclin D1, pRb, p53 and p27 protein expression

    Directory of Open Access Journals (Sweden)

    Colquhoun Alison

    2009-03-01

    Full Text Available Abstract Background Gamma-linolenic acid is a known inhibitor of tumour cell proliferation and migration in both in vitro and in vivo conditions. The aim of the present study was to determine the mechanisms by which gamma-linolenic acid (GLA osmotic pump infusion alters glioma cell proliferation, and whether it affects cell cycle control and angiogenesis in the C6 glioma in vivo. Methods Established C6 rat gliomas were treated for 14 days with 5 mM GLA in CSF or CSF alone. Tumour size was estimated, microvessel density (MVD counted and protein and mRNA expression measured by immunohistochemistry, western blotting and RT-PCR. Results GLA caused a significant decrease in tumour size (75 ± 8.8% and reduced MVD by 44 ± 5.4%. These changes were associated with reduced expression of vascular endothelial growth factor (VEGF (71 ± 16% and the VEGF receptor Flt1 (57 ± 5.8% but not Flk1. Expression of ERK1/2 was also reduced by 27 ± 7.7% and 31 ± 8.7% respectively. mRNA expression of matrix metalloproteinase-2 (MMP2 was reduced by 35 ± 6.8% and zymography showed MMP2 proteolytic activity was reduced by 32 ± 8.5%. GLA altered the expression of several proteins involved in cell cycle control. pRb protein expression was decreased (62 ± 18% while E2F1 remained unchanged. Cyclin D1 protein expression was increased by 42 ± 12% in the presence of GLA. The cyclin dependent kinase inhibitors p21 and p27 responded differently to GLA, p27 expression was increased (27 ± 7.3% while p21 remained unchanged. The expression of p53 was increased (44 ± 16% by GLA. Finally, the BrdU incorporation studies found a significant inhibition (32 ± 11% of BrdU incorporation into the tumour in vivo. Conclusion Overall the findings reported in the present study lend further support to the potential of GLA as an inhibitor of glioma cell proliferation in vivo and show it has direct effects upon cell cycle control and angiogenesis. These effects involve changes in protein

  15. Studies on the relationship of pleiotrophin and MMP2 with the clinicopathological features of invasive breast carcinoma

    Directory of Open Access Journals (Sweden)

    Bo ZHANG

    2012-08-01

    Full Text Available Objective To study the correlation between the expressions of both pleitropin (PTN and matrix metalloproteinase-2 (MMP2 to the clinicopathological features of patients with breast cancer. Methods The pathological specimens were collected from 103 cases of invasive breast cancer, including 51 cases of triple negative breast cancer (TNBC, i.e. all the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 were negatively expressed and 52 cases of non-TNBC. Ten specimens of paraneoplastic tissue were also collected as controls. The expressions of PTN and MMP2 were detected with immunohistochemical method, and the correlation of PTN and MMP2 expressions to the clinicopathological features of breast cancer (age, tumor size, histopathological grading and axillary lymph node metastases was assessed. Results Among the 103 patients with breast cancer, no statistical difference was found between TNBC group and non-TNBC group in age of onset, tumor size and the axillary lymph node metastasis (P > 0.05, but significant difference was found in histopathological grading (P < 0.05. The positive rate of PTN expression was 83.5% (86/103, and of MMP2 expression was 68% (70/103, and no significant difference was found between TNBC group and non-TNBC group. The expressions of PTN and MMP2 were correlated with the age of onset, histopathological grading and axillary lymph node metastasis, but showed poor consistency in breast cancer (Kappa coefficient=0.1817, 95% CI=-0.0091-0.3726; Z=2.0212, P=0.0433. Conclusions The expression of PTN and MMP2 is correlated with the age, histopathological grading and axillary lymph node metastasis of patients with invasive breast cancer, and not correlated with TNBC. The expression of PTN and MMP2 shows poor consistency in invasive breast cancer.

  16. A PKC-dependent recruitment of MMP-2 controls semaphorin-3A growth-promoting effect in cortical dendrites.

    Directory of Open Access Journals (Sweden)

    Bertrand Gonthier

    Full Text Available There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3. Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites. The in situ analysis of MMP-2 expression and activity is consistent with a functional growth assay demonstrating in vitro that the pharmacological inhibition of MMP-2 reduces the growth of cortical dendrites in response to Sema3A. Hence, our results suggest that the selective recruitment and activation of MMP-2 in response to Sema3A requires a PKC alpha dependent mechanism. Altogether, we provide a second set of data supporting MMPs as effectors of the growth-promoting effects of semaphorins, and we identify the potential signalling pathway involved.

  17. Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity

    Directory of Open Access Journals (Sweden)

    Sheng-Teng Huang

    2011-01-01

    Full Text Available This study aimed to assess the potential anti-angiogenic mechanism of Phyllanthus urinaria (P. urinaria and characterize the major compound in P. urinaria that exerts anti-angiogenic effect. The water extract of P. urinaria and Ellagic Acid were used to evaluate the anti-angiogenic effect in chorioallantoic membrane (CAM in chicken embryo and human vascular endothelial cells (HUVECs. The matrix metalloproteinase-2 (MMP-2 activity was determined by gelatin zymography. The mRNA expressions of MMP-2, MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2 were analyzed by reverse transcription polymerase chain reaction (RT-PCR. Level of MMP-2 proteins in conditioned medium or cytosol was determined by western blot analysis. We confirmed that P. urinaria's in vivo anti-angiogenic effect was associated with a reduction in MMP-2 activity. Ellagic acid, one of the major polyphenolic components as identified in P. urinaria by high performance liquid chromatography mass spectrometry (HPLC/MS, exhibited the same anti-angiogenic effect in vivo. Both P. urinaria and Ellagic Acid inhibited MMP-2 activity in HUVECs with unchanged mRNA level. The mRNA expression levels of MMP-14 and TIMP-2 were not altered either. Results from comparing the change of MMP-2 protein levels in conditioned medium and cytosol of HUVECs after the P. urinaria or Ellagic Acid treatment revealed an inhibitory effect on the secretion of MMP-2 protein. This study concluded that Ellagic Acid is the active compound in P. urinaria to exhibit anti-angiogenic activity and to inhibit the secretion of MMP-2 protein from HUVECs.

  18. Expression of the MMP-2 and TIMP-2 Protein and Its mRNA in Rats with Acute Lung Injury Caused by Lipopolysaccharide%急性肺损伤大鼠肺组织基质金属蛋白酶2及其抑制因子蛋白和mRNA的表达

    Institute of Scientific and Technical Information of China (English)

    阮琼; 苏中昊; 杨爱东; 李文雯; 汪东颖; 吴中华; 庞慧芳

    2011-01-01

    Objective To investigate the changes of NF-κB, MMP-2 and TIMP-2 protein and its mRNA in the rats with acute lung injury (ALI) caused by lipopolysaccharide ( LPS ).Methods Twenty male Wistar rats were randomly divided into two groups: normal control group, LPS model group.Each group had two subgroups, 4 hours and 8 hours after LPS were injected.The ALI model was established by intravenous injection of LPS ( 10 mg/kg)through a tailvein.Then the white blood cell (WBC) in blood and the protein content in bronchial alveolar lavage fluid (BALF) were measured, the expressions of nuclear factor-κB (NF-κB) , matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinases (TIMP-2) protein in pulmonary tissues were measured by immunohistochemistry ABC , the expression NF-κB , MMP-2 and TIMP-2mRNA were measured by real-time fluorescent polymerase chain reaction(PCR) ,while the histopathology of the lung injury was observed by light microscope.Results Compared with normal group, the expression of NF-κB and MMP-2 protien dyeing positive rate of area and its mRNA in LPS model group were obviously increased at 4 hours and 8 hours ( P < 0.01 ) , and the expression of TIMP-2 protein dyeing positive rate of area and its mRNA at 4 hours and 8 hours were obviously decreased in LPS model group (P < 0.05or P < 0.01 ).Light microscope observation indicated that there were pulmonary hemorrhage and necrosis in model group.Conclusion The increasing of expression NF-κB and MMP-2 protein and its mRNA and the decreasing of expression TIMP-2 protein and its mRNA may be the mechanism of ALI caused by LPS.%目的 探讨内毒素致急性肺损伤(ALI)大鼠肺组织核转录因子-kB ( NF-κB)、基质金属蛋白酶2(MMP-2)及其抑制因子(TIMP-2 )蛋白和mRNA表达的变化.方法 20只雄性Wistar大鼠随机分为2组:对照组、US模型组,每组再分为4h和8h两个亚组.尾静脉注射脂多搪(LPS) (10 mg/kg )建立大鼠急性肺损伤模型.检侧

  19. Matrix Metalloproteinase-2 (MMP-2) Gene Deletion Enhances MMP-9 Activity, Impairs PARP-1 Degradation, and Exacerbates Hepatic Ischemia and Reperfusion Injury in Mice.

    Science.gov (United States)

    Kato, Hiroyuki; Duarte, Sergio; Liu, Daniel; Busuttil, Ronald W; Coito, Ana J

    2015-01-01

    Hepatic ischemia and reperfusion injury (IRI) is an inflammatory condition and a significant cause of morbidity and mortality after surgery. Matrix metalloproteinases (MMPs) have been widely implicated in the pathogenesis of inflammatory diseases. Among the different MMPs, gelatinases (MMP-2 and MMP-9) are within the most prominent MMPs detected during liver IRI. While the role of MMP-9 in liver damage has been fairly documented, direct evidence of the role for MMP-2 activity in hepatic IRI remains to be established. Due to the lack of suitable inhibitors to target individual MMPs in vivo, gene manipulation is as an essential tool to assess MMP direct contribution to liver injury. Hence, we used MMP-2-/- deficient mice and MMP-2+/+ wild-type littermates to examine the function of MMP-2 activity in hepatic IRI. MMP-2 expression was detected along the sinusoids of wild-type livers before and after surgery and in a small population of leukocytes post-IRI. Compared to MMP-2+/+ mice, MMP-2 null (MMP-2-/-) mice showed exacerbated liver damage at 6, 24, and 48 hours post-reperfusion, which was fatal in some cases. MMP-2 deficiency resulted in upregulation of MMP-9 activity, spontaneous leukocyte infiltration in naïve livers, and amplified MMP-9-dependent transmigration of leukocytes in vitro and after hepatic IRI. Moreover, complete loss of MMP-2 activity impaired the degradation of poly (ADP-ribose) polymerase (PARP-1) in extensively damaged livers post-reperfusion. However, the administration of a PARP-1 inhibitor to MMP-2 null mice restored liver preservation to almost comparable levels of MMP-2+/+ mice post-IRI. Deficient PARP-1 degradation in MMP-2-null sinusoidal endothelial cells correlated with their increased cytotoxicity, evaluated by the measurement of LDH efflux in the medium. In conclusion, our results show for the first time that MMP-2 gene deletion exacerbates liver IRI. Moreover, they offer new insights into the MMP-2 modulation of inflammatory responses

  20. 芪苈强心胶囊对心衰大鼠 MMP-2、MMP-9表达的影响%The Effects of Qiliqiangxin Capsules on the Protein Expression of MMP-2,MMP-9 in Rat Heart Failure Model

    Institute of Scientific and Technical Information of China (English)

    赵伟涛; 徐增政; 贾桂贞; 罗世国

    2016-01-01

    Objective :To investigate the changes of matrix metalloproteinases (MMP‐2 ,MMP‐9) in rat heart failure model ,and the relationships between MMPs and heart failure and the effects of Qiliqiangxin Capsules on it in a rat model .Methods :Thirty male SD rats were randomly divided into three groups :control group ,heart failure (model) group and heart failure + Qiliqiangxin Capsules(treated) group .Research:(1)The change of cardiac function evaluated by echocardiography ;(2)the change of blood flow dynamics ;(3)the change of tissue morphology ;(4)the protein ex‐pression of MMP‐2 ,MMP‐9 were examined by immunohistochemical analysis .Results:The average of the grave scale of protein expression of the MMP‐2(119 .22 ± 9 .13) ,MMP‐9(121 .31 ± 5 .36)in model group are lower than these of the control group obviously (P<0 .01);after Qiliqiangxin Capsules treatment ,the average of the grave scale of protein ex‐pression of MMP‐2 (159 .53 ± 5 .37) ,MMP‐9(155 .62 ± 4 .57)are higher than these of the model group prominently (P<0 .01) .Conclusion:MMP‐2 ,MMP‐9 are involved in the cardiac extracellular matrix remodeling and heart failure .Qil‐iqiangxin Capsules can improve heart failure rat cardiac function and hemodynamics ,the effect may be related to reduc‐ing the high expression of MMP‐2 and MMP‐9 in myocardial tissue inhibiting myocardial remodeling.%目的:观察基质金属蛋白酶‐2、‐9(MMP‐2、MMP‐9)在心力衰竭大鼠模型中的变化,并采用芪苈强心胶囊进行治疗干预,以确定芪苈强心胶囊对M M Ps的影响及其在治疗心力衰竭过程中可能的作用机制。方法:30只雄性SD大鼠随机分为三组:对照组、心力衰竭组(模型组)、心力衰竭+芪苈强心胶囊组(治疗组)。进行以下研究:(1)心脏超声功能改变;(2)大鼠血流动力学变化;(3)组织形态学变化;(4)免疫组化检测心肌组织MMP‐2、MMP‐9的蛋白表达

  1. 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.

  2. Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas

    OpenAIRE

    Costa, Angela Margarida; Pinto, Filipe; Martinho, Olga; Oliveira, Maria José; Jordan, Peter; Reis,R.M.

    2014-01-01

    Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade extracellular matrix (ECM), thus assisting invasion. Upregulation of MMPs, frequently reported in gliomas, is associated with aggressive behavior. WNK2 is a tumor suppressor gene expressed in normal brain, and silenced by promoter methylation in gliomas. Patients without WNK2 exhibited poor prognosis, and its downregulation was associated with increased glioma cell invasion. Here we showed that MMP2 expression and activity ...

  3. Selective gene transfer to endometrial cancer cells by a polymer against matrix metalloproteinase 2 (MMP-2).

    Science.gov (United States)

    Han, Joo Youn; Choi, Dong Soon; Kim, Changhoon; Joo, Hyun; Min, Churl K

    2008-04-01

    A novel cancer-cell-specific gene delivery vector with high transfection efficiency was designed and tested with an in vitro coculture consisting of the human endometrial adenocarcinoma cell line, HEC-1A cells, and normal endometrial stromal cells. For the cancer-cell targeting, polyethylenimine (PEI), a cationic polymer that can be easily combined with anionic DNA to form a particulate complex, polyplex, being capable of transferring a gene into a variety of cells, was covalently conjugated with antibodies against matrix metalloproteinase 2 (MMP-2), a typical surface-marker protein on cancer cells known for its close correlation with angiogenesis and invasion in many types of cancer, using the heterofunctional cross-linker, n-succinimidyl 3-(2-pyridyldithio)-propionamide. Biophysical properties and transfection efficiencies of anti-MMP-2-conjugated PEI were analyzed by means of dynamic light scattering, laser Doppler anemometry, and flow cytometry. Our results reveal that (1) the PEI-anti-MMP-2 antibody conjugate maintains physical parameters, including sizes and surface charges, which appear to be favorable for gene transfer and (2) when the pEGFP-N3 plasmid complexes of the PEI-anti-MMP-2 antibody conjugate are applied to the coculture consisting of HEC-1A cells and human stromal cells, a high level of green fluorescent protein expression occurs in HEC-1A cells over stromal cells, suggesting a specific gene transfer targeting cancer cells. Therefore, targeting invading cancer cells with the PEI-anti-MMP-2 antibody conjugate could be promising in endometrial cancer treatment, and this gene delivery system deserves further optimization in the context of targeted therapeutic gene delivery.

  4. 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.

  5. Expression of MMP-2 and TIMP-2 in placenta organization of normal full-term pregnancy and hypertensive disorder complicating pregnancy%MMP-2及TIMP-2在正常足月妊娠与妊娠期高血压疾病胎盘组织中的表达

    Institute of Scientific and Technical Information of China (English)

    连李斌; 袁宁霞

    2015-01-01

    目的:探究基质金属蛋白酶-2(matrix metallopreteinases -2,MMP-2)与基质蛋白酶组织抑制因子-2(tissue inhibitor of metallopreteinases -2,TIMP-2)在正常足月妊娠与妊娠期高血压疾病胎盘组织中的表达。方法选择2012~2014年陕西中医学院第二附属医院妇产科收治的住院期间诊断有妊娠期高血压疾病的产妇60例作为观察组,健康正常足月妊娠的产妇60例作为对照组。检测分析两组产妇胎盘MMP-2与TIMP-2的表达情况。结果两组产妇TIMP-2水平比较差异无统计学意义( P>0.05);观察组MMP-2水平与免疫组化积分均显著低于对照组( P<0.05)。结论 MMP-2在妊娠期高血压疾病产妇的胎盘组织内呈低表达,导致胎盘组织内滋养细胞的浸润能力明显下降,与产妇妊娠期高血压疾病的发病密切相关,是胎盘发生病理改变的基础。%Objective To explore the expression of matrix metallopreteinases -2 ( MMP -2 ) and tissue inhibitor of metallopreteinases -2 ( TIMP-2 ) in placenta organization of normal full -term pregnancy and hypertensive disorder complicating pregnancy .Methods 60 cases with hypertensive disorder complicating pregnancy in the The Second Affiliated Hospital of Shanxi College of Traditional Chinese Medicine from 2012 to 2014 were selected as observation group .60 cases of normal full -term pregnancy were selected as control group , The expression of MMP -2 and TIMP-2 of two groups were measured .Results TIMP-2 level between two groups had no statistically significant difference ( P >0.05 ) .MMP -2 level and immunohistochemical integral in observation group were significantly lower than the control group ( P<0.05 ) .Conclusion The MMP-2 has a low expression in placenta organization of hypertensive disorder complicating pregnancy leading to the invasion ability of trophoblast cells in placenta tissues decreased significantly , which is closely related to

  6. Src promotes cutaneous wound healing by regulating MMP-2 through the ERK pathway.

    Science.gov (United States)

    Wu, Xue; Yang, Longlong; Zheng, Zhao; Li, Zhenzhen; Shi, Jihong; Li, Yan; Han, Shichao; Gao, Jianxin; Tang, Chaowu; Su, Linlin; Hu, Dahai

    2016-03-01

    Wound healing is a highly orchestrated, multistep process, and delayed wound healing is a significant symptomatic clinical problem. Keratinocyte migration and re-epithelialization play the most important roles in wound healing, as they determine the rate of wound healing. In our previous study, we found that Src, one of the oldest proto‑oncogenes encoding a membrane-associated, non-receptor protein tyrosine kinase, promotes keratinocyte migration. We therefore hypothesized that Src promotes wound healing through enhanced keratinocyte migration. In order to test this hypothesis, vectors for overexpressing Src and small interfering RNAs (siRNAs) for silencing of Src were used in the present study. We found that the overexpression of Src accelerated keratinocyte migration in vitro and promoted wound healing in vivo without exerting a marked effect on cell proliferation. The extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways play important roles in Src-accelerated keratinocyte migration. Further experiments demonstrated that Src induced the protein expression of matrix metalloproteinase-2 (MMP-2) and decreased the protein expression of E-cadherin. We suggest that ERK signaling is involved in the Src-mediated regulation of MMP-2 expression. The present study provided evidence that Src promotes keratinocyte migration and cutaneous wound healing, in which the regulation of MMP-2 through the ERK pathway plays an important role, and thus we also demonstrated a potential therapeutic role for Src in cutaneous wound healing.

  7. Expression of Matrix Metalloproteinase in Cervical Squamous Cell Carcinoma Tissue and Its Significance%子宫颈鳞癌组织中基质金属蛋白酶MMP-2和MMP-9的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    张淑兰; 林蓓; 蔡威; 牛菊敏

    2003-01-01

    目的:探讨基质金属蛋白酶MMP-2和MMP-9与宫颈鳞癌的发生、发展及转移的关系.方法:免疫组化S-P法测定MMP-2和MMP-9表达及分布;明胶酶谱法测定活性型MMP-2及MMP-9蛋白的含量;RT-PCR技术检测MMP-2及MMP-9 mRNA表达水平.结果:宫颈癌组织中MMP-2及MMP-9的阳性表达率为77.78%和66.67%,明显高于在CIN(10%及20%)及正常宫颈组织中表达率.淋巴转移组MMP-2及MMP-9的阳性率均显著高于非淋巴转移组,P<0.05.在宫颈鳞癌组织中MMP-2及MMP-9酶活性显著高于CIN及正常宫颈组织,P<0.01.MMP-2及MMP-9 mRNA在宫颈鳞癌中的表达量亦显著高于在CIN及正常宫颈组织的表达量,P<0.01.结论:MMP-2及MMP-9与宫颈鳞癌的发生、发展及转移有关,MMP-2及MMP-9的增高可作为判断宫颈鳞癌具有转移倾向的临床参考指标.

  8. Role of immunohistochemical overexpression of matrix metalloproteinases MMP-2 and MMP-11 in the prognosis of death by ovarian cancer.

    Science.gov (United States)

    Périgny, Martine; Bairati, Isabelle; Harvey, Isabelle; Beauchemin, Michel; Harel, François; Plante, Marie; Têtu, Bernard

    2008-02-01

    Matrix metalloproteinases (MMPs) are enzymes thought to be involved in tumor invasion. We hypothesized that MMP-2 and MMP-11 overexpression was associated with the aggressiveness of ovarian carcinoma. This study was performed on samples from 100 patients with stage III ovarian carcinomas treated surgically between 1990 and 2000. Immunohistochemical staining was performed on ovarian tumors and peritoneal implants using monoclonal antibodies. Overexpression was defined as more than 10% of cells expressing the marker. Multivariate analyses showed that only MMP-2 overexpression by cancer cells in peritoneal implants was associated with a significant risk of death by disease (hazard ratio, 2.65; 95% confidence interval, 1.41-4.97; P =.003). MMP-11 overexpression was not predictive of survival. These results suggest that MMP-2 overexpression by cancer cells in peritoneal implants and not in the primary ovarian cancer is predictive of ovarian cancer prognosis and more likely reflects the presence of particularly aggressive clones of cancer cells.

  9. 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.

  10. 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.

  11. Downregulation of matrix metalloproteinase-2 (MMP-2) utilizing adenovirus-mediated transfer of small interfering RNA (siRNA) in a novel spinal metastatic melanoma model.

    Science.gov (United States)

    Tsung, Andrew J; Kargiotis, Odysseas; Chetty, Chandramu; Lakka, Sajani S; Gujrati, Meena; Spomar, Daniel G; Dinh, Dzung H; Rao, Jasti S

    2008-03-01

    Matrix metalloproteinases (MMPs) comprise a class of secreted zinc-dependent endopeptidases implicated in the metastatic potential of tumor cells due to their ability to degrade the extracellular matrix (ECM) and basement membrane. Matrix metalloproteinase-2 (MMP-2) has been detected in high levels and correlates with invasiveness in human melanoma. We have studied the effect of adenovirus-mediated transfer of small interfering RNA (siRNA) against MMP-2 in the human melanoma cell line A2058. The delivery of these double-stranded RNA molecules represents an efficient technology in silencing disease-causing genes with known sequences at the post-transcriptional level. siRNA against MMP-2 mRNA (Ad-MMP-2) was found to decrease MMP-2 protein expression and activity in melanoma cells as demonstrated by western blotting and gelatin zymography. Furthermore, infection of cells with Ad-MMP-2 inhibited cellular migration and invasion as indicated by spheroid and matrigel assays. We also observed dose-dependent suppression of vascular network formation in an angiogenesis assay. Finally, we developed a nude mouse spinal metastatic model to investigate the local effects of tumor metastasis. Intravenous tail vein injection with Ad-MMP-2 on days 5, 9 and 11 after tumor implantation resulted in complete retention of neurological function as compared to control and scrambled vector (Ad-SV)-treated groups that showed complete paraplegia by day 14+/-2 days. Hematoxylin and eosin staining revealed decreased tumor size in the Ad-MMP-2-treated animals. This novel experimental model revealed that adenoviral-mediated transfer of RNA interference against MMP-2 results in the retention of neurological function and significantly inhibited tumor growth.

  12. Gene expression profiles of some cytokines, growth factors, receptors, and enzymes (GM-CSF, IFNγ, MMP-2, IGF-II, EGF, TGF-β, IGF-IIR) during pregnancy in the cat uterus.

    Science.gov (United States)

    Agaoglu, Ozgecan Korkmaz; Agaoglu, Ali Reha; Guzeloglu, Aydin; Aslan, Selim; Kurar, Ercan; Kayis, Seyit Ali; Schäfer-Somi, Sabine

    2016-03-01

    Early pregnancy is one of the most critical periods of pregnancy, and many factors such as cytokines, enzymes, and members of the immune system have to cooperate in a balanced way. In the present study, the gene expression profiles of factors associated with pregnancy such as EGF, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, interferon gamma, insulin-like growth factor 2, insulin-like growth factor 2 receptor, and matrix metalloproteinase 2 were analyzed in uterine tissues of female cats. The cats were assigned to five groups: G1 (embryo positive, n = 7; 7th day after mating), G2 (after implantation, n = 7; 20th day after mating), G3 (midgestation, n = 7; 24-25th day after mating), G4 (late gestation, n = 7; 30-45th day after mating), G5 (oocyte group, n = 7; 7th day after estrus). Tissue samples from the uterus and placenta were collected after ovariohysterectomy. Relative messenger RNA levels were determined by real-time polymerase chain reaction. All the factors examined were detected in all tissue samples. In the course of pregnancy, significantly higher expression of EGF and matrix metalloproteinase 2 in G2 than in G1 was observed (P < 0.05). Insulin-like growth factor 2 expression was higher in all groups than in G1 (P < 0.05). Upregulation of EGF during implantation was detected. The expression of interferon gamma was significantly higher in G3 than in G1 (P < 0.05). Transforming growth factor beta and granulocyte-macrophage colony-stimulating factor were constantly expressed in all groups. In conclusion, the expressions of these factors in feline uterine tissue at different stages of pregnancy might indicate that these factors play roles in the development of pregnancy such as trophoblast invasion, vascularization, implantation, and placentation.

  13. MMP2-cleavage of DMP1 generates a bioactive peptide promoting differentiation of dental pulp stem/progenitor cell

    Directory of Open Access Journals (Sweden)

    C Chaussain

    2009-11-01

    Full Text Available Dentin Matrix Protein 1 (DMP1 plays a regulatory role in dentin mineralization and can also function as a signaling molecule. MMP-2 (matrix metalloproteinase-2 is a predominant protease in the dentin matrix that plays a prominent role in tooth formation and a potential role during the carious process. The possibility that MMP-2 can cleave DMP1 to release biologically active peptides was investigated in this study. DMP1, both in the recombinant form and in its native state within the dentin matrix, was shown to be a substrate for MMP-2. Proteolytic processing of DMP1 by MMP-2 produced two major peptides, one that contains the C-terminal region of the protein known to carry both the ASARM (aspartic acid and serine rich domain domain involved in biomineralization and the DNA binding site of DMP1. In vitro experiments with recombinant N- and C-terminal polypeptides mimicking the MMP-2 cleavage products of DMP1 demonstrated an effect of the C-polypeptide on the differentiation of dental pulp stem/progenitor cells to a putative odontoblast phenotype. In vivo implantation of this peptide in a rat injured pulp model induced a rapid formation of a homogeneous dentin bridge covered by a palisade of orientated cells expressing dentin sialoprotein (DSP and DMP1, attesting an efficient repair process. These data suggest that a peptide generated through the proteolytic processing of DMP1 by MMP-2 can regulate the differentiation of mesenchymal cells during dentinogenesis and thus sustain reparative dentin formation in pathological situations such as carious decay. In addition, these data open a new therapeutic possibility of using this peptide to regenerate dentin after an injury.

  14. 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.

  15. 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.

  16. Enhancement of Matrix Metalloproteinase-2 (MMP-2 as a Potential Chondrogenic Marker during Chondrogenic Differentiation of Human Adipose-Derived Stem Cells

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    Yoshie Arai

    2016-06-01

    Full Text Available Human adipose-derived stem cells (hASCs have a capacity to undergo adipogenic, chondrogenic, and osteogenic differentiation. Recently, hASCs were applied to various fields including cell therapy for tissue regeneration. However, it is hard to predict the direction of differentiation of hASCs in real-time. Matrix metalloproteinases (MMPs are one family of proteolytic enzymes that plays a pivotal role in regulating the biology of stem cells. MMPs secreted by hASCs are expected to show different expression patterns depending on the differentiation state of hASCs because biological functions exhibit different patterns during the differentiation of stem cells. Here, we investigated proteolytic enzyme activity, especially MMP-2 activity, in hASCs during their differentiation. The activities of proteolytic enzymes and MMP-2 were higher during chondrogenic differentiation than during adipogenic and osteogenic differentiation. During chondrogenic differentiation, mRNA expression of MMP-2 and the level of the active form of MMP-2 were increased, which also correlated with Col II. It is concluded that proteolytic enzyme activity and the level of the active form of MMP-2 were increased during chondrogenic differentiation, which was accelerated in the presence of Col II protein. According to our findings, MMP-2 could be a candidate maker for real-time detection of chondrogenic differentiation of hASCs.

  17. Enhancement of Matrix Metalloproteinase-2 (MMP-2) as a Potential Chondrogenic Marker during Chondrogenic Differentiation of Human Adipose-Derived Stem Cells.

    Science.gov (United States)

    Arai, Yoshie; Park, Sunghyun; Choi, Bogyu; Ko, Kyoung-Won; Choi, Won Chul; Lee, Joong-Myung; Han, Dong-Wook; Park, Hun-Kuk; Han, Inbo; Lee, Jong Hun; Lee, Soo-Hong

    2016-06-17

    Human adipose-derived stem cells (hASCs) have a capacity to undergo adipogenic, chondrogenic, and osteogenic differentiation. Recently, hASCs were applied to various fields including cell therapy for tissue regeneration. However, it is hard to predict the direction of differentiation of hASCs in real-time. Matrix metalloproteinases (MMPs) are one family of proteolytic enzymes that plays a pivotal role in regulating the biology of stem cells. MMPs secreted by hASCs are expected to show different expression patterns depending on the differentiation state of hASCs because biological functions exhibit different patterns during the differentiation of stem cells. Here, we investigated proteolytic enzyme activity, especially MMP-2 activity, in hASCs during their differentiation. The activities of proteolytic enzymes and MMP-2 were higher during chondrogenic differentiation than during adipogenic and osteogenic differentiation. During chondrogenic differentiation, mRNA expression of MMP-2 and the level of the active form of MMP-2 were increased, which also correlated with Col II. It is concluded that proteolytic enzyme activity and the level of the active form of MMP-2 were increased during chondrogenic differentiation, which was accelerated in the presence of Col II protein. According to our findings, MMP-2 could be a candidate maker for real-time detection of chondrogenic differentiation of hASCs.

  18. Captopril and lisinopril only inhibit matrix metalloproteinase-2 (MMP-2) activity at millimolar concentrations.

    Science.gov (United States)

    Kuntze, Luciana B; Antonio, Raquel C; Izidoro-Toledo, Tatiane C; Meschiari, Cesar A; Tanus-Santos, Jose E; Gerlach, Raquel F

    2014-03-01

    Matrix metalloproteinase-2 (MMP-2) shares structural similarities with the angiotensin-converting enzyme (ACE). ACE inhibitors have been described to inhibit MMP-2, but this inhibitory potential was not shown using a highly purified MMP-2. This study aimed to investigate the inhibitory potential of captopril and lisinopril regarding MMP-2 activity. The first objective was to test the potential of captopril to change the pH of the buffer solution. The second objective was to test the direct inhibitory effect of captopril and lisinopril on plasma MMP-2 and on recombinant human MMP-2 (rhMMP-2). The in vitro activity assays included gelatin zymography and a fluorimetric assay. Captopril solubilization significantly decreased the pH of the 50 mM Tris buffer solution at the following concentrations: 2 mM (p MMP-2 and rhMMP-2 showed that inhibition only happened at captopril concentrations ≥ 4 and 1 mM, respectively (p MMP-2 (p MMP-2 are 3 orders of magnitude higher than those present in vivo after drug administration. We also discuss possible pitfalls for gelatinase inhibitory assays (besides the obvious pH problem already cited). In conclusion, this study's data show that captopril and lisinopril did not inhibit MMP-2 directly at the concentrations reached in vivo.

  19. 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.

  20. MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2.

    Directory of Open Access Journals (Sweden)

    Jie Ding

    Full Text Available Our study was approved by the Medical Ethics Committee of Tang Du Hospital, Fourth Military Medical University and complied strictly with national ethical guidelines. Preeclampsia (PE is a specific clinical disorder characterized by gestational hypertension and proteinuria and is a leading cause of maternal and perinatal mortality worldwide. The miR-519d-3p is upregulated in the maternal plasma of patients with PE which indicates a possible association between this microRNA and the pathogenesis of PE. No studies to date have addressed the effect of miR-519d-3p on the invasion and migration of trophoblast cells. In our study, we found that miR-519d-3p expression was elevated in placental samples from patients with PE. In vitro, overexpression of miR-519d-3p significantly inhibited trophoblast cell migration and invasion, whereas transfection of a miR-519d-3p inhibitor enhanced trophoblast cell migration and invasion. Luciferase assays confirmed that matrix metalloproteinase-2 (MMP-2 is a direct target of miR-519d-3p. Quantitative real-time PCR and western blot assays showed that overexpression of miR-519d-3p downregulated MMP-2 mRNA and protein expression. Knockdown of MMP-2 using a siRNA attenuated the increased trophoblast migration and invasion promoted by the miR-519d-3p inhibitor. In placentas from patients with PE or normal pregnancies, a negative correlation between the expression of MMP-2 and miR-519d-3p was observed using the Pearson correlation and linear regression analysis. Our present findings suggest that upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2; miR-519d-3p may represent a potential predictive and therapeutic target for PE.

  1. LPS Induces Occludin Dysregulation in Cerebral Microvascular Endothelial Cells via MAPK Signaling and Augmenting MMP-2 Levels

    Directory of Open Access Journals (Sweden)

    Lan-hui Qin

    2015-01-01

    Full Text Available Disrupted blood-brain barrier (BBB integrity contributes to cerebral edema during central nervous system infection. The current study explored the mechanism of lipopolysaccharide- (LPS- induced dysregulation of tight junction (TJ proteins. Human cerebral microvascular endothelial cells (hCMEC/D3 were exposed to LPS, SB203580 (p38MAPK inhibitor, or SP600125 (JNK inhibitor, and cell vitality was determined by MTT assay. The proteins expressions of p38MAPK, JNK, and TJs (occludin and zonula occludens- (ZO- 1 were determined by western blot. The mRNA levels of TJ components and MMP-2 were measured with quantitative real-time polymerase chain reaction (qRT-PCR, and MMP-2 protein levels were determined by enzyme-linked immunosorbent assay (ELISA. LPS, SB203580, and SP600125 under respective concentrations of 10, 7.69, or 0.22 µg/mL had no effects on cell vitality. Treatment with LPS decreased mRNA and protein levels of occludin and ZO-1 and enhanced p38MAPK and JNK phosphorylation and MMP-2 expression. These effects were attenuated by pretreatment with SB203580 or SP600125, but not in ZO-1 expression. Both doxycycline hyclate (a total MMP inhibitor and SB-3CT (a specific MMP-2 inhibitor partially attenuated the LPS-induced downregulation of occludin. These data suggest that MMP-2 overexpression and p38MAPK/JNK pathways are involved in the LPS-mediated alterations of occludin in hCMEC/D3; however, ZO-1 levels are not influenced by p38MAPK/JNK.

  2. DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells.

    Science.gov (United States)

    Olaso, E; Ikeda, K; Eng, F J; Xu, L; Wang, L H; Lin, H C; Friedman, S L

    2001-11-01

    Type I collagen provokes activation of hepatic stellate cells during liver injury through mechanisms that have been unclear. Here, we tested the role of the discoidin domain tyrosine kinase receptor 2 (DDR2), which signals in response to type I collagen, in this pathway. DDR2 mRNA and protein are induced in stellate cells activated by primary culture or in vivo during liver injury. The receptor becomes tyrosine phosphorylated in response to either endogenous or exogenous type I collagen, whereas its expression is downregulated during cellular quiescence induced by growth on Matrigel. We developed stellate cell lines stably overexpressing either wild-type DDR2, a constitutively active chimeric DDR2 receptor (Fc-DDR2), a truncated receptor expressing the extracellular domain, or a kinase-dead DDR2 Cells overexpressing DDR2 showed enhanced proliferation and invasion through Matrigel, activities that were directly related to increased expression of active matrix metalloproteinase 2 (MMP-2). These data show that DDR2 is induced during stellate cell activation and implicate the phosphorylated receptor as a mediator of MMP-2 release and growth stimulation in response to type I collagen. Moreover, type I collagen-dependent upregulation of DDR2 expression establishes a positive feedback loop in activated stellate cells, leading to further proliferation and enhanced invasive activity.

  3. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hee [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Warrington, Junie P.; Sonntag, William E. [Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Lee, Yong Woo, E-mail: ywlee@vt.edu [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States)

    2012-04-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  4. Matrix metalloproteinase 2 (MMP-2) degrades soluble vasculotropic amyloid-beta E22Q and L34V mutants, delaying their toxicity for human brain microvascular endothelial cells.

    Science.gov (United States)

    Hernandez-Guillamon, Mar; Mawhirt, Stephanie; Fossati, Silvia; Blais, Steven; Pares, Mireia; Penalba, Anna; Boada, Merce; Couraud, Pierre-Olivier; Neubert, Thomas A; Montaner, Joan; Ghiso, Jorge; Rostagno, Agueda

    2010-08-27

    Patients carrying mutations within the amyloid-beta (Abeta) sequence develop severe early-onset cerebral amyloid angiopathy with some of the related variants manifesting primarily with hemorrhagic phenotypes. Matrix metalloproteases (MMPs) are typically associated with blood brain barrier disruption and hemorrhagic transformations after ischemic stroke. However, their contribution to cerebral amyloid angiopathy-related hemorrhage remains unclear. Human brain endothelial cells challenged with Abeta synthetic homologues containing mutations known to be associated in vivo with hemorrhagic manifestations (AbetaE22Q and AbetaL34V) showed enhanced production and activation of MMP-2, evaluated via Multiplex MMP antibody arrays, gel zymography, and Western blot, which in turn proteolytically cleaved in situ the Abeta peptides. Immunoprecipitation followed by mass spectrometry analysis highlighted the generation of specific C-terminal proteolytic fragments, in particular the accumulation of Abeta-(1-16), a result validated in vitro with recombinant MMP-2 and quantitatively evaluated using deuterium-labeled internal standards. Silencing MMP-2 gene expression resulted in reduced Abeta degradation and enhanced apoptosis. Secretion and activation of MMP-2 as well as susceptibility of the Abeta peptides to MMP-2 degradation were dependent on the peptide conformation, with fibrillar elements of AbetaE22Q exhibiting negligible effects. Our results indicate that MMP-2 release and activation differentially degrades Abeta species, delaying their toxicity for endothelial cells. However, taking into consideration MMP ability to degrade basement membrane components, these protective effects might also undesirably compromise blood brain barrier integrity and precipitate a hemorrhagic phenotype.

  5. MMP-2及TIMP-1、TIMP-2在自然流产绒毛和蜕膜组织中的表达及意义%Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1,2 in chorionic villi and deciduas from women with spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    吕荟明; 孙状壮; 李力男; 宋巍; 王卓然

    2010-01-01

    目的 探讨基质金属蛋白酶-2(MMP-2)及金属蛋白酶组织抑制剂-1(TIMP-1)和金属蛋白酶组织抑制剂-2(TIMP-2)在早孕自然流产绒毛和蜕膜组织中的表达及意义.方法 采用S-P免疫组织化学染色的方法,对31例自然流产者(实验组)及36例人工流产者(对照组)绒毛及蜕膜组织中MMP-2和TIMP-2的表达进行分析;采用逆转录聚合酶链反应(RT-PCR)技术对绒毛组织中MMP-2及TIMP-1的mRNA表达量进行分析.结果 无论是绒毛组织还是蜕膜组织中MMP-2的表达两组之间均无统计学差异;但实验组两种组织中的TIMP-2强阳性(Ⅲ级)表达率均显著低于对照组(P<0.01);实验组TIMP-1 mRNA的表达量显著低于对照组(P<0.05).结论 自然流产绒毛和蜕膜组织中MMP-2的正常表达及TIMP-1、TIMP-2的低表达导致MMP-2与TIMP-1及TIMP-2的比值升高,该比值失调可能与自然流产发生有关.

  6. Effect of simulated high altitude hypoxia on matrix metalloproteinase-2 expression in serum of rats with chronic periodontitis%模拟高原缺氧对慢性牙周炎大鼠血清中MMP-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    孔耀; 刘鲁川; 周霞; 刘福玉; 杨苏平; 张海元

    2010-01-01

    目的 研究常氧与缺氧条件下慢性牙周炎大鼠血清中基质金属蛋白酶2(matrix metalloproteinase-2, MMP-2)的表达变化,探讨MMP-2与高原牙周病的关系.方法 模拟高原缺氧建立大鼠慢性牙周炎模型,采用ELISA法测定正常对照组、常氧牙周炎组、缺氧对照组、缺氧牙周炎组大鼠血清中MMP-2表达.结果 正常对照组、常氧牙周炎组、缺氧对照组、缺氧牙周炎组血清中MMP-2浓度分别为(92.00±21.78)、(118.09±25.01)、(102.03±21.30)、(159.19±34.13) ng/ml,常氧牙周炎组与正常对照组、缺氧牙周炎组与缺氧对照组、缺氧对照组与正常对照组、缺氧牙周炎组与常氧牙周炎组比较均有统计学意义(P<0.01).其中缺氧牙周炎组血清中MMP-2浓度升高最为显著(P<0.01).结论 缺氧上调血清中MMP-2的表达,进而促进大鼠牙周组织的破坏.

  7. 浅表性膀胱癌中MMP-2和TlMP-2的表达及其与肿瘤复发和进展的关系%Expression of matrix metalloproteinase-2, tissue inhibitor of metaloproteinase-2 insuperficial carcinoma of bladder and its correlation with tumor recurrence and progression

    Institute of Scientific and Technical Information of China (English)

    李原学; 舒心雨; 范治璐; 孙卫兵

    2005-01-01

    目的该实验旨在探讨MMP-2和TIMP-2在浅表性膀胱癌中的表达特点及其与肿瘤复发及进展的关系.方法选取随访资料完整的因膀胱癌而行的膀胱部分切除的病例61例(1995~1997),行常规病理学检查.采用SP免疫组织化学方法,检测61例膀胱癌组织中的7例正常膀胱黏膜的MMP-2和TIMP-2的表达情况.结果正常膀胱黏膜中,MMP-2和TIMP-2均为阴性表达.在61例膀胱癌中,MMP-2的阳性表达为28例,阳性率为45.9%(28/61),MMp-2的表达主要位于肿瘤细胞的细胞质内;TIMP-2在肿瘤细胞的细胞质及间质中均有表达,阳性率分别为50.8%(31/61)和54.1%(33/61).MMP-2和TIMP-2的表达和肿瘤细胞的病理分级的高低无相关性;TIMP-2间质表达阳性组中浅表性膀胱癌的2年复发率明显高于表达阳性组;在已复发的33例膀胱癌中,MMP-2表达阳性组中进展成为浸润性癌的比率明显高于表达阴性组.结论TIMP-2在间质中的表达可作为浅表性膀胱癌复发的预后指标.MMP-2表达阳性的浅表性膀胱癌在复发过程中易进展为浸润性癌.

  8. 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.

  9. 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

  10. CD147与类风湿关节炎成纤维样滑膜细胞MMPs合成的关系%Enhanced production of MMP-2, MMP-9 by fibroblast cells from rheumatoid arthritis patients when co-cultured with monocytes of high CD147 expression

    Institute of Scientific and Technical Information of China (English)

    吴振彪; 朱平; 卢宁; 史战国; 樊春梅; 王彦宏

    2006-01-01

    目的观察类风湿性关节炎(rheumatoid arthritis, RA)患者成纤维样滑膜细胞(fibroblast-like synoviocytes, FLS)与高表达CD147的单核细胞株(THP-1)共培养后,基质金属蛋白酶(matrix metalloproteinases,MMPs)合成的变化.方法从手术切除的RA患者滑膜组织中,分离FLS,经流式细胞术测定CD14,CD68及免疫组化测定波形纤维蛋白(vimentin)证实后,传代培养.将FLS与高表达 CD147的THP-1共培养,观察THP-1细胞对FLS MMPs合成的影响.用明胶酶谱法测FLS MMP-2,MMP-9含量.同时观察CD147拮抗肽(AP9)对MMPs表达的影响.结果高表达CD147,低表达MMP-2、 MMP-9的THP-1细胞与CD147表达水平低的RA FLS混合培养后,FLS合成MMP-2、 MMP-9水平显著升高,随着THP-1细胞数的增加,MMP-2、 MMP-9的合成量也增加.THP-1对FLS合成MMP-2、 MMP-9的刺激作用可被CD147拮抗肽AP-9所抑制.结论高表达CD147的THP-1细胞对共培养的RA FLS合成MMP-2、MMP-9有刺激作用,这种刺激作用可被CD147拮抗肽AP-9所抑制,提示THP-1表面的CD147对FLS合成MMPs有促进作用.

  11. 兔颈动脉粥样硬化斑块内MMP-2与新生血管关系的研究%The relationship between MMP-2 and the neovascularization in rabbit carotid atherosclerotic plaque

    Institute of Scientific and Technical Information of China (English)

    樊建华

    2011-01-01

    To detect the relationship between matrix metaloproteinase -2 (MMP -2) and the neova - scularization in rabbit carotid atherosclerotic model plaque, forty of the male New Zealand white rabbits were randomly divided into 4 groups: group A (the blank control group), group B (high-cholesterol diet group), group C (silicone collar intervention and high-cholesterol diet for 14 days group), group D (silicone collar intervention and high -cholesterol diet for 28 days group). We used contrast -enhanced ultrasound (CEUS) to detect the neovascularization in the carotid atherosclerosis plaque. The expressions of MMP-2 and cluster of differentiation 31 (CD31) were assessed by immunohistochemical staining, and we analyzed the correlations between them. CEUS showed that the neovascularization in the carotid atherosclerotic model plaques was statistical difference between the C and D group (P < 0.05); immunohistochemistry showed there were positive MMP-2 and CD31 expressions in the plaques, and the correlative analysis showed the expressions were positive correlated (P < 0.01). We can conclude that MMP-2 play some roles in the neovascularization within the rabbit carotid atherosclerotic plaques.%目的 探讨兔颈动脉粥样硬化模型斑块内基质金属蛋白酶-2(matrix metaloproteinase-2,MMP-2)与新生血管的关系.方法 将40只健康雄性新西兰大白兔随机分为4组,A组予普通饲料喂养28 d、B组予高脂饮食28 d、C组予硅橡胶圈干预联合高脂饮食14d、D组予硅橡胶圈干预联合高脂饮食28 d.利用超声造影检测C组、D组兔颈动脉粥样硬化模型斑块内新生血管情况,应用免疫组化检测斑块内MMP-2、血小板内皮细胞黏附分子-1(cluster of differentiation 31,CD31)的表达,进行两者间相关性分析.结果 超声造影检测到C组、D组模型兔颈动脉斑块内有新生血管形成,两组间差异有统计学意义(P<0.05).免疫组化结果显示斑块内有阳性表达的MMP-2、CD31,

  12. Fucoidan/FGF-2 induces angiogenesis through JNK- and p38-mediated activation of AKT/MMP-2 signalling

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beom Su [Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Bonecell Biotech Inc., 77, Dunsan-dong, Seo-gu, Daejeon 302-830 (Korea, Republic of); Park, Ji-Yun [Bonecell Biotech Inc., 77, Dunsan-dong, Seo-gu, Daejeon 302-830 (Korea, Republic of); Kang, Hyo-Jin [Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Hyung-Jin [Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Lee, Jun, E-mail: omslee@wku.ac.kr [Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Bonecell Biotech Inc., 77, Dunsan-dong, Seo-gu, Daejeon 302-830 (Korea, Republic of)

    2014-08-08

    Graphical abstract: Schematic diagram of the angiogenic activity mechanism by FGF-2/fucoidan treatment in HUVECs. Fucoidan enhances the FGF-2-induced phosphorylation of p38, JNK, and ERK MAPKs. However, p38 and JNK were involved in AKT phosphorylation and MMP-2 activation and resulted in enhanced angiogenic activity, such as tube formation and migration, in HUVECs. - Highlights: • The angiogenic activity of fucoidan in HUVECs was explored. • Fucoidan enhanced HUVEC proliferation, migration, and tube formation. • Fucoidan enhanced angiogenesis through p38 and JNK but not ERK in HUVECs. • Fucoidan targeted angiogenesis-mediated AKT/MMP-2 signalling in HUVECs. - Abstract: Angiogenesis is an important biological process in tissue development and repair. Fucoidan has previously been shown to potentiate in vitro tube formation in the presence of basic fibroblast growth factor (FGF-2). However, the underlying molecular mechanism remains largely unknown. This study was designed to investigate the action of fucoidan in angiogenesis in human umbilical vein endothelial cells (HUVECs) and to explore fucoidan-signalling pathways. First, we evaluated the effect of fucoidan on cell proliferation. Matrigel-based tube formation and wound healing assays were performed to investigate angiogenesis. Matrix metalloproteinase-2 (MMP-2) mRNA expression and activity levels were analysed by reverse transcription polymerase chain reaction (RT-PCR) and zymography, respectively. Additionally, phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was detected by Western blot. The results indicate that fucoidan treatment significantly increased cell proliferation in the presence of FGF-2. Moreover, compared to the effect of FGF-2 alone, fucoidan and FGF-2 had a greater effect on tube formation and cell migration, and this effect was found to be synergistic. Furthermore, fucoidan enhanced the phosphorylation of extracellular signal-regulated kinase (ERK

  13. Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways.

    Science.gov (United States)

    Qian, Liqiang; Liu, Yan; Xu, Yang; Ji, Weidan; Wu, Qiuye; Liu, Yongjing; Gao, Quangen; Su, Changqing

    2015-11-01

    Matrine, a sophora alkaloid, has been demonstrated to exert antitumor effects on many types of cancer. However, its bioactivity is weak and its potential druggability is low. We modified the structure of matrine and obtained a new matrine derivative, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities than matrine. In this study, we investigated the antitumor activity and the underlying mechanisms of WM130 on hepatocellular carcinoma (HCC) cells in vitro and in vivo, and found that WM130 inhibited the proliferation, invasion, migration and induced apoptosis of HCC cells in a dose-dependent manner. Furthermore, after treatment with WM130, the expressions of p-EGFR, p-ERK, p-AKT, MMP-2 and the ratio of Bcl-2/Bax were significantly down-regulated, whereas the expression of PTEN was increased in HCC cells. Moreover, WM130 inhibited Huh-7 xenograft tumor growth in a dose-dependent manner after intravenous administration. Immunohistochemistry results demonstrated that WM130 treatment resulted in down-regulation of p-EGFR, MMP-2, and Ki67 and up-regulation of PTEN. The findings indicated that WM130 could inhibit cell proliferation, invasion, migration and induced apoptosis in HCC cells by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways and may be a novel effective candidate for HCC treatment.

  14. Effects of maternal diabetes on male offspring: high cell proliferation and increased activity of MMP-2 in the ventral prostate.

    Science.gov (United States)

    Damasceno, A A; Carvalho, C P; Santos, E M B; Botelho, F V; Araújo, F A; Deconte, S R; Tomiosso, T C; Balbi, A P C; Zanon, R G; Taboga, S R; Góes, R M; Ribeiro, D L

    2014-10-01

    This study presents a comprehensive view of the histological and functional status of the prostate of adult rat offspring of mothers subjected to gestational diabetes induced by alloxan. The ventral prostate of male adult offspring of diabetic (DP) or normal (CP) mothers was evaluated for collagen fibres, cell death, fibroblasts, smooth muscle cells, cell proliferation, matrix metalloproteinases (MMPs), androgen receptors (AR), transforming growth factor β1 (TGFβ-1), catalase and total antioxidant activity. The prostates of DP animals were lower in weight than those of the CP group. The DP group also exhibited hyperglycaemia and hypotestosteronemia, higher cell proliferation and AR expression, a reduction in α-actin (possibly interfering with the reproductive function of the prostate), and enhanced activity of MMP-2, although the absolute content of MMP-2 was lower in this group. These findings were associated with increased TGFβ-1 and decreased collagen distribution. The prostates of DP rats additionally exhibited reductions in catalase and total antioxidant activity. Thus, rats developing in a diabetic intrauterine environment have glycaemic and hormonal changes that impact on the structure and physiology of the prostate in adulthood. The increased AR expression possibly leads to elevated cell proliferation. Stromal remodelling was characterized by enhanced activity of MMP-2 and collagen degradation, even with increased TGFβ-1 activation. These changes associated with increased oxidative stress might interfere with tissue architecture and glandular homeostasis.

  15. THE EXPRESSIONS AND THEIR SIGNIFICANCE OF MATRIX METALLOPROTEINASE-2 AND Ki67 IN CERVICAL CANCER BEFORE AND AFTER INTERVENTIONAL CHEMOTHERAPY%宫颈癌介入化疗前后MMP-2和Ki67表达及意义

    Institute of Scientific and Technical Information of China (English)

    杨秀凤; 魏晓强; 张文华

    2010-01-01

    目的 探讨MMP-2和Ki67在宫颈癌介入化疗前后表达的变化及其对预测介入化疗敏感性的作用.方法 在介入化疗前后用免疫组化方法测定46例宫颈癌组织MMP-2、Ki67蛋白的表达.结果 宫颈癌介入化疗临床总有效率为78.26%,介入化疗有效率与临床期别无关(χ2=0.161,P>0.05).介入化疗前后宫颈癌组织中MMP-2、Ki67蛋白的表达差异均有显著性(χ2=4.792、5.134,P0.05);介入化疗前Ki67阳性者介入化疗有效率为83.78%,Ki67阴性者介入化疗有效率为55.56%,两者比较差异有显著性(χ2=7.521,P<0.05).结论 介入化疗能显著改变宫颈癌组织中MMP-2和Ki67蛋白的阳性表达率,抑制肿瘤细胞的增殖和浸润;介入化疗前检测宫颈癌组织中Ki67蛋白的表达可能用于预测介入化疗的临床疗效.

  16. 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.

  17. Leptin promotes human endometriotic cell migration and invasion by up-regulating MMP-2 through the JAK2/STAT3 signaling pathway.

    Science.gov (United States)

    Ahn, Ji-Hye; Choi, Youn Seok; Choi, Jung-Hye

    2015-10-01

    Despite evidence that leptin may play a role in the pathogenesis of endometriosis, the specific function of leptin in the migration and invasion of endometriotic cells is not well characterized. In this study, we investigated the effect of leptin on the migration, invasion and matrix metalloproteinase (MMP) expression levels of human endometriotic cells. We found that leptin stimulated the migration and invasion of endometriotic cells (11Z, 12Z and 22B) in a dose-dependent manner. Leptin receptor (ObR) siRNA significantly inhibited the migration and invasion induced by leptin in 11Z and 12Z cells. Leptin-induced migration and invasion were significantly attenuated by pretreatment with SB-3CT, a specific gelatinase (MMP-2 and MMP-9) inhibitor. In addition, leptin-induced increases in the mRNA and protein expression and enzyme activity of MMP-2 in 11Z and 12Z cells. Selectively inhibiting MMP-2 using siRNA and an inhibitor (GM6003), impaired the ability of leptin to stimulate the migration and invasion of endometriotic cells, suggesting that MMP-2 plays an essential role in leptin-induced migration and invasion. Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) inhibitor (AG490) significantly inhibited the migration, invasion and MMP-2 expression induced by leptin in endometriotic cells. Furthermore, the Extracellular signal-Regulated Kinase inhibitor PD98059 neutralized the migration and invasion promoting effects of leptin. Taken together, these results suggest that leptin may contribute to the migration and invasion abilities of endometriotic cells via the up-regulation of MMP-2 through an ObR-dependent JAK2/STAT3 signaling pathway.

  18. MMP-2、MMP-9及其抑制因子TIMP-1、TIMP-2在宫颈癌中的表达%Expression and significance of matrix metalloproteinase and tissu inhibitor of matrix metalloproteinase in cervical cancer

    Institute of Scientific and Technical Information of China (English)

    游泳; 杜莹莹; 曹媛; 李真珍; 张胜军

    2014-01-01

    目的 分析基质金属蛋白酶2(MMP-2)和MMP-9及其抑制因子1(TIMP-1)和TIMP-2在宫颈癌不同位置中的表达情况及其临床意义.方法 选取经病理证实的宫颈浸润癌患者118例(ICC组)、宫颈上皮内瘤样病变患者75例(CIN组),取病变中心组织和边缘组织;选取正常宫颈组织标本45例为对照组.采用SABC法行免疫组化检测各组中MMP-2、MMP-9、TIMP-1和TIMP-2因子表达阳性率、染色强度和表达强度.比较各组相关因子表达情况差异.结果 ICC组中MMP-2和MMP-9的阳性率、染色强度和表达强度显著高于CIN组和对照组,TIMP-1和TIMP-2的阳性率、染色强度和表达强度显著低于CIN组和对照组(P<0.05).在ICC组,边缘癌组织的MMP-2与MMP-9的阳性率、染色强度和表达强度明显高于中心癌组织,而TIMP-1与TIMP-2的阳性率、染色强度和表达强度明显低于中心癌组织(P<0.05).结论 MMP-2、MMP-9及其抑制因子TIMP-1、TIMP-2与宫颈癌的发生、发展密切相关,可能在宫颈癌的侵袭与转移中发挥着重要作用.

  19. MMP-2/9-Specific Activatable Lifetime Imaging Agent

    Directory of Open Access Journals (Sweden)

    Marcus T.M. Rood

    2015-05-01

    Full Text Available Optical (molecular imaging can benefit from a combination of the high signal-to-background ratio of activatable fluorescence imaging with the high specificity of luminescence lifetime imaging. To allow for this combination, both imaging techniques were integrated in a single imaging agent, a so-called activatable lifetime imaging agent. Important in the design of this imaging agent is the use of two luminophores that are tethered by a specific peptide with a hairpin-motive that ensured close proximity of the two while also having a specific amino acid sequence available for enzymatic cleavage by tumor-related MMP-2/9. Ir(ppy3 and Cy5 were used because in close proximity the emission intensities of both luminophores were quenched and the influence of Cy5 shortens the Ir(ppy3 luminescence lifetime from 98 ns to 30 ns. Upon cleavage in vitro, both effects are undone, yielding an increase in Ir(ppy3 and Cy5 luminescence and a restoration of Ir(ppy3 luminescence lifetime to 94 ns. As a reference for the luminescence activation, a similar imaging agent with the more common Cy3-Cy5 fluorophore pair was used. Our findings underline that the combination of enzymatic signal activation with lifetime imaging is possible and that it provides a promising method in the design of future disease specific imaging agents.

  20. Dimerization of endogenous MT1-MMP is a regulatory step in the activation of the 72-kDa gelatinase MMP-2 on fibroblasts and fibrosarcoma cells

    DEFF Research Database (Denmark)

    Ingvarsen, S.; Madsen, D.H.; Hillig, T.

    2008-01-01

    with monovalent Fab fragments. Since only a negligible level of proMMP-2 activation was obtained with MT1-MMP-expressing cells in the absence of dimerization, our results identify the dimerization event as a critical level of proteolytic cascade regulation Udgivelsesdato: 2008/7...... by a monoclonal antibody that binds specifically to MT1-MMP as shown by immunofluorescence experiments. The antibody has no effect on the catalytic activity. The effect on proMMP-2 activation involves MT1-MMP dimerization because it requires the divalent monoclonal antibody, with no effect obtained...

  1. Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.

    Directory of Open Access Journals (Sweden)

    Kyo Won Seo

    Full Text Available Increased blood pressure, leading to mechanical stress on vascular smooth muscle cells (VSMC, is a known risk factor for vascular remodeling via increased activity of matrix metalloproteinase (MMP within the vascular wall. This study aimed to identify cell surface mechanoreceptors and intracellular signaling pathways that influence VSMC to produce MMP in response to mechanical stretch (MS. When VSMC was stimulated with MS (0-10% strain, 60 cycles/min, both production and gelatinolytic activity of MMP-2, but not MMP-9, were increased in a force-dependent manner. MS-enhanced MMP-2 expression and activity were inhibited by molecular inhibition of Akt using Akt siRNA as well as by PI3K/Akt inhibitors, LY293002 and AI, but not by MAPK inhibitors such as PD98059, SP600125 and SB203580. MS also increased Akt phosphorylation in VSMC, which was attenuated by AG1295, a PDGF receptor (PDGFR inhibitor, but not by inhibitors for other receptor tyrosine kinase including EGF, IGF, and FGF receptors. Although MS activated PDGFR-α as well as PDGFR-β in VSMC, MS-induced Akt phosphorylation was inhibited by molecular deletion of PDGFR-β using siRNA, but not by inhibition of PDGFR-α. Collectively, our data indicate that MS induces MMP-2 production in VSMC via activation of Akt pathway, that is mediated by activation of PDGFR-β signaling pathways.

  2. Fucoidan/FGF-2 induces angiogenesis through JNK- and p38-mediated activation of AKT/MMP-2 signalling.

    Science.gov (United States)

    Kim, Beom Su; Park, Ji-Yun; Kang, Hyo-Jin; Kim, Hyung-Jin; Lee, Jun

    2014-08-08

    Angiogenesis is an important biological process in tissue development and repair. Fucoidan has previously been shown to potentiate in vitro tube formation in the presence of basic fibroblast growth factor (FGF-2). However, the underlying molecular mechanism remains largely unknown. This study was designed to investigate the action of fucoidan in angiogenesis in human umbilical vein endothelial cells (HUVECs) and to explore fucoidan-signalling pathways. First, we evaluated the effect of fucoidan on cell proliferation. Matrigel-based tube formation and wound healing assays were performed to investigate angiogenesis. Matrix metalloproteinase-2 (MMP-2) mRNA expression and activity levels were analysed by reverse transcription polymerase chain reaction (RT-PCR) and zymography, respectively. Additionally, phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was detected by Western blot. The results indicate that fucoidan treatment significantly increased cell proliferation in the presence of FGF-2. Moreover, compared to the effect of FGF-2 alone, fucoidan and FGF-2 had a greater effect on tube formation and cell migration, and this effect was found to be synergistic. Furthermore, fucoidan enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and AKT. MMP-2 activation was also significantly increased. Specific inhibitors of p38 (SB203580) and JNK (SP600125) inhibited tube formation and wound healing, while an ERK inhibitor (PD98059) did not. MMP-2 activation and AKT phosphorylation were also attenuated and associated with the suppression of p38 and JNK phosphorylation, but not with that of ERK. These results indicate that fucoidan, in the presence of FGF-2, induces angiogenesis through AKT/MMP-2 signalling by activating p38 and JNK. These findings provide basic molecular information on the effect of fucoidan on angiogenesis in the presence of FGF-2.

  3. Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Naoki [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kubota, Yoshitaka, E-mail: kubota-cbu@umin.ac.jp [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kosaka, Kentarou; Akita, Shinsuke; Sasahara, Yoshitarou; Kira, Tomoe [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kuroda, Masayuki [Center for Advanced Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Mitsukawa, Nobuyuki [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Bujo, Hideaki [Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University, Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, #285-8741 (Japan); Satoh, Kaneshige [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan)

    2015-08-07

    Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDR may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings.

  4. MMP-2的抑制作用在治疗大鼠口腔溃疡中的实验研究%Effects of Inhibiting the Activity of MMP-2 on Oral Ulcers in Rats

    Institute of Scientific and Technical Information of China (English)

    刘振宇; 张立田; 蔡攀; 李正强; 陈黄琴

    2013-01-01

    Objective:To explore the therapeutic effects of inhibiting the activity of MMP-2(matrix metalloproteinase-2) on the experimental rats' oral ulcers.Methods:The oral ulcer models of rats were induced by 75 % acetic acid and SD rats were randomly allocated to Doxycycline intervention groups and control group.1,3,5,7days after Doxycycline intervention,the general conditions of the rats,the damage of oral mucosa under the naked eye,the mucosal pathological changes,Masson collagen trichrome staining and expression levels of MMP-2 under the optic microscope were observed.Results:At the same time point,Doxycycline could reduce inflammatory exudation and lighten Masson collagen staining.The positive integrated optic density (IOD) of the cells in the intervention group was remarkably lower than the control group (P<0.01).The IOD of the higher dose and lower dose group was 2186.56 ± 926.41 and 5416.12 ± 941.56,respectively,and there was statistical difference between these two groups (P<0.01).Conclusion:MMP-2 activity inhibition can improve the healing of oral ulcer in concentration-dependent manner.Within a limited range of concentration,the higher the concentrations are,the more obvious effects are.%目的:探究抑制基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)的活性对于实验性大鼠口腔溃疡的治疗效果.方法:采用浓度为75%醋酸溶液制备大鼠口腔溃疡模型,待造模成功后随机分组,各组每天给予不同浓度的强力霉素进行干预(对照组不用强力霉素).分别在1、3、5、7d观察大鼠的全身状况、肉眼下黏膜损伤情况、光镜下溃疡黏膜病理改变情况以及组织切片中Masson胶原三色染色、MMP-2的表达水平.结果:同一时间点,强力霉素干预组炎性渗出少,胶原Masson染色颜色较浅.干预组MMP-2的累积光密度值(integrated optical density,IOD)显著低于对照组(P<0.01),其中大剂量组ICD值为2186.56±926.41,小剂量组为5416.12±941.56,

  5. RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2011-07-28

    We previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70\\/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered. In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours. Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.

  6. RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation.

    Science.gov (United States)

    Walsh, Naomi; Larkin, AnneMarie; Swan, Niall; Conlon, Kevin; Dowling, Paul; McDermott, Ray; Clynes, Martin

    2011-07-28

    We previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered. In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours. Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.

  7. Identification of collagen binding domain residues that govern catalytic activities of matrix metalloproteinase-2 (MMP-2).

    Science.gov (United States)

    Mikhailova, Margarita; Xu, Xiaoping; Robichaud, Trista K; Pal, Sanjay; Fields, Gregg B; Steffensen, Bjorn

    2012-01-01

    An innovative approach to enhance the selectivity of matrix metalloproteinase (MMP) inhibitors comprises targeting these inhibitors to catalytically required substrate binding sites (exosites) that are located outside the catalytic cleft. In MMP-2, positioning of collagen substrate molecules occurs via a unique fibronectin-like domain (CBD) that contains three distinct modular collagen binding sites. To characterize the contributions of these exosites to gelatinolysis by MMP-2, seven MMP-2 variants were generated with single, or concurrent double and triple alanine substitutions in the three fibronectin type II modules of the CBD. Circular dichroism spectroscopy verified that recombinant MMP-2 wild-type (WT) and variants had the same fold. Moreover, the MMP-2 WT and variants had the same activity on a short FRET peptide substrate that is hydrolyzed independently of CBD binding. Among single-point variants, substitution in the module 3 binding site had greatest impact on the affinity of MMP-2 for gelatin. Simultaneous substitutions in two or three CBD modules further reduced gelatin binding. The rates of gelatinolysis of MMP-2 variants were reduced by 20-40% following single-point substitutions, by 60-75% after double-point modifications, and by >90% for triple-point variants. Intriguingly, the three CBD modules contributed differentially to cleavage of dissociated α-1(I) and α-2(I) collagen chains. Importantly, kinetic analyses (k(cat)/K(m)) revealed that catalysis of a triple-helical FRET peptide substrate by MMP-2 relied primarily on the module 3 binding site. Thus, we have identified three collagen binding site residues that are essential for gelatinolysis and constitute promising targets for selective inhibition of MMP-2.

  8. Relationship Between Unstable Angina Pectoris CHD and MMP-1, MMP-2 and MMP-3%冠心病不稳定型心绞痛与MMP-1、MMP-2、MMP-3相关性研究

    Institute of Scientific and Technical Information of China (English)

    王莹威; 蒋宁; 高嵩山; 魏明慧

    2013-01-01

    目的:研究冠心病不稳定型心绞痛(UA)患者血清MMP-1、MMP-2、MMP-3的表达,并探讨其与冠状动脉狭窄程度和斑块不稳定性之间的关系.方法:分离出30例UA和30例CPS患者血清,采用酶联免疫吸附法(ELISA)检测其中的MMP-1、MMP-2、MMP-3表达水平,并进行相关性研究.结果:UA和CPS组患者血清中MMP-1、MMP-2、MMP-3有统计学意义(P<0.005).结论:冠心病不稳定型心绞痛患者血清中MMP-1、MMP-2、MMP-3表达水平增高,提示其可能是动脉粥样硬化不稳定斑块的发病机制之一.%Objective:To investigate patients with unstable angina(UA) serum expressions of MMP-1,MMP-2 and M MP-3,and explore the relationship between the coronary stenosis and plaque instability.Methods:The serum from 30 patients with UA and 30 patients with CPS was isolated in which MMP-1,MMP-2,MMP-3 expression levels were tested by enzyme-linked immunosorbent assay (ELISA),and related research was carried on.Results:UA and CPS groups' MMP-1,MMP-2,MMP-3 expressions had statistical significance(P < 0.005).Conclusion:The serum expression levels of MMP-1,MMP-2 and MMP -3 in coronary heart disease patients with unstable angina were increased,suggesting that it may be one of the unstable plaque pathogenesis of atherosclerosis.

  9. The regulation of matrix metalloproteinases by Id1 in gastric cancer%由Id1介导的MMP-2、MMP-9对胃癌生成的调控作用

    Institute of Scientific and Technical Information of China (English)

    雷婷; 韩霜; 郭雪艳; 丁杰

    2011-01-01

    Background and purpose: Angiogenesis is critical for the development of all malignancies.Id transcription factors have been shown to regulate key steps in tumor growth and metastasis due to their effects on angiogenesis.This study investigated the possible relationship between Id1 and matrix metalloproteinases (MMPs)in angiogenesis of gastric cancer.Methods: Expressions of Id1 and MMPs in gastric cancer tissues were examined by immunohistochemistry.The human gastric cancer SGC7901 sub-cell lines expressing Id1-siRNA was established.Expressions of MMP-2 and MMP-9 in Id1-siRNA transfectants were examined by semi-quantitative RT-PCR and Western blot.Enzyme activity of MMP-2 and MMP-9 in Id1-siRNA cells were detected by zymography method.Expressions of MMP-2 and MMP-9 in Id1-siRNA cell-transplanted tumor tissues in nude mice were identified by immunohistochemical method and Western blot.Results: Id1 and MMP-2, MMP-9 co-expressions were identified in the gastric cancer tissues.Significantly decreased expressions of both Id1 and MMP-2, MMP-9 on both protein and mRNA levels in SGC7901 Id1-siRNA transfectants were found.Data from zymography method showed that the activations of MMPs in Id1-siRNA cell lines were reduced compared to the control groups.Decreased expression of MMP-2 and MMP-9 in the Id1-siRNA transplanted tumor tissues in nude mice were found compared to those from the control cells.Conclusion: Id1 and MMP-2, MMP-9 were co-expressed in gastric cancer tissues; Id1 could upregulate the expression of MMP-2 and MMP-9 in gastric cancer.Downregulation of Id1 in the gastric cancer cells inhibited the transcriptional activities of MMP-2 and MMP-9.So we presumed that Id1 might promote tumorigenesis by transactivating MMP-2 and MMP-9 in gastric cancer.%背景与目的:肿瘤血管生成是肿瘤的一大重要特性,肿瘤微血管密度已被作为许多恶性肿瘤预后的一个重要指标.分化抑制因子(Id)是新近发现的与血管

  10. Hypoxia induces a phenotypic switch of fibroblasts to myofibroblasts through a MMP-2/TIMP mediated pathway: Implications for venous neointimal hyperplasia in hemodialysis access

    Science.gov (United States)

    Misra, Sanjay; Fu, Alex A.; Misra, Khamal D.; Shergill, Uday M.; Leof, Edward B; Mukhopadhyay, Debabrata

    2010-01-01

    Purpose Hemodialysis grafts fail because of venous neointimal hyperplasia formation caused by adventitial fibroblasts which have become myofibroblasts (α-smooth muscle actin positive cells) and migrate to the neointima. There is increased expression of hypoxia inducible factor-1 alpha (HIF-1α in venous neointimal hyperplasia formation in experimental animal model and clinical samples. We hypothesized that under hypoxic stimulus (HIF-1α fibroblasts will convert to myofibroblasts through a matrix metalloproteinase-2 (MMP-2) mediated pathway. Materials and methods Murine AKR-2B fibroblasts were made hypoxic or normoxic for 24, 48, and 72 hours. Protein expression for HIF-1α, α-smooth muscle actin, MMP-2, MMP-9, TIMP-1, and TIMP-2 was performed to determine the kinetic changes of these proteins. Immunostaining for α-smooth muscle actin, collagen, and fibronectin was performed. Results At all time points, there was significantly increased expression of HIF-1α in the hypoxic fibroblasts when compared to normoxic fibroblasts (P<0.05). There was significantly increased expression α-smooth muscle actin at all time points which peaked by 48 hours in hypoxic fibroblasts when compared to normoxic fibroblasts (P<0.05). There was a significant increase in the expression of active MMP-2 by 48-72 hours and a significant increase in tissue inhibitor of metalloproteinase-1 (TIMP-1) by 48-72 hours by hypoxic fibroblasts (P<0.05). By 72 hours, there was significant increase in TIMP-2 expression (P<0.05). Immunohistochemical analysis demonstrated increased expression for α-smooth muscle actin, collagen, and fibronectin as the length of hypoxia increased. Conclusions Under hypoxia, fibroblasts will convert to myofibroblasts through a MMP-2 mediated pathway which may provide insight into the mechanism of venous neointimal hyperplasia. PMID:20434368

  11. Zinc-chelation contributes to the anti-angiogenic effect of ellagic acid on inhibiting MMP-2 activity, cell migration and tube formation.

    Directory of Open Access Journals (Sweden)

    Sheng-Teng Huang

    Full Text Available BACKGROUND: Ellagic acid (EA, a dietary polyphenolic compound, has been demonstrated to exert anti-angiogenic effect but the detailed mechanism is not yet fully understood. The aim of this study was to investigate whether the zinc chelating activity of EA contributed to its anti-angiogenic effect. METHODS AND PRINCIPAL FINDINGS: The matrix metalloproteinases-2 (MMP-2 activity, a zinc-required reaction, was directly inhibited by EA as examined by gelatin zymography, which was reversed dose-dependently by adding zinc chloride. In addition, EA was demonstrated to inhibit the secretion of MMP-2 from human umbilical vein endothelial cells (HUVECs as analyzed by Western blot method, which was also reversed by the addition of zinc chloride. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK, known to down-regulate the MMP-2 activity, was induced by EA at both the mRNA and protein levels which was correlated well with the inhibition of MMP-2 activity. Interestingly, zinc chloride could also abolish the increase of EA-induced RECK expression. The anti-angiogenic effect of EA was further confirmed to inhibit matrix-induced tube formation of endothelial cells. The migration of endothelial cells as analyzed by transwell filter assay was suppressed markedly by EA dose-dependently as well. Zinc chloride could reverse these two effects of EA also in a dose-dependent manner. Since magnesium chloride or calcium chloride could not reverse the inhibitory effect of EA, zinc was found to be involved in tube formation and migration of vascular endothelial cells. CONCLUSIONS/SIGNIFICANCE: Together these results demonstrated that the zinc chelation of EA is involved in its anti-angiogenic effects by inhibiting MMP-2 activity, tube formation and cell migration of vascular endothelial cells. The role of zinc was confirmed to be important in the process of angiogenesis.

  12. Neurokinin-1 receptor directly mediates glioma cell migration by up-regulation of matrix metalloproteinase-2 (MMP-2) and membrane type 1-matrix metalloproteinase (MT1-MMP).

    Science.gov (United States)

    Mou, Lingyun; Kang, Yawei; Zhou, Ying; Zeng, Qian; Song, Hongjing; Wang, Rui

    2013-01-04

    Neurokinin-1 receptor (NK1R) occurs naturally on human glioblastomas. Its activation mediates glioma cell proliferation. However, it is unknown whether NK1R is directly involved in tumor cell migration. In this study, we found human hemokinin-1 (hHK-1), via NK1R, dose-dependently promoted the migration of U-251 and U-87 cells. In addition, we showed that hHK-1 enhanced the activity of MMP-2 and the expression of MMP-2 and MT1-matrix metalloproteinase (MMP), which were responsible for cell migration, because neutralizing the MMPs with antibodies decreased cell migration. The involved mechanisms were then investigated. In U-251, hHK-1 induced significant calcium efflux; phospholipase C inhibitor U-73122 reduced the calcium mobilization, the up-regulation of MMP-2 and MT1-MMP, and the cell migration induced by hHK-1, which meant the migration effect of NK1R was mainly mediated through the G(q)-PLC pathway. We further demonstrated that hHK-1 boosted rapid phosphorylation of ERK, JNK, and Akt; inhibition of ERK and Akt effectively reduced MMP-2 induction by hHK-1. Meanwhile, inhibition of ERK, JNK, and Akt reduced the MT1-MMP induction. hHK-1 stimulated significant phosphorylation of p65 and c-JUN in U-251. Reporter gene assays indicated hHK-1 enhanced both AP-1 and NF-κB activity; inhibition of ERK, JNK, and Akt dose-dependently suppressed the NF-κB activity; only the inhibition of ERK significantly suppressed the AP-1 activity. Treatment with specific inhibitors for AP-1 or NF-κB strongly blocked the MMP up-regulation by hHK-1. Taken together, our data suggested NK1R was a potential regulator of human glioma cell migration by the up-regulation of MMP-2 and MT1-MMP.

  13. Matrix metalloproteinase-2 (MMP-2) generates soluble HLA-G1 by cell surface proteolytic shedding.

    Science.gov (United States)

    Rizzo, Roberta; Trentini, Alessandro; Bortolotti, Daria; Manfrinato, Maria C; Rotola, Antonella; Castellazzi, Massimiliano; Melchiorri, Loredana; Di Luca, Dario; Dallocchio, Franco; Fainardi, Enrico; Bellini, Tiziana

    2013-09-01

    Human leukocyte antigen-G (HLA-G) molecules are non-classical HLA class I antigens with an important role in pregnancy immune regulation and inflammation control. Soluble HLA-G proteins can be generated through two mechanisms: alternative splicing and proteolytic release, which is known to be metalloprotease mediated. Among this class of enzymes, matrix metalloproteinases (MMPs) might be involved in the HLA-G1 membrane cleavage. Of particular interest are MMP-2 and MMP-9, which regulate the inflammatory process by cytokine and chemokine modulation. We evaluated the effect of MMP-9 and MMP-2 on HLA-G1 membrane shedding. In particular, we analyzed the in vitro effect of these two gelatinases on the secretion of HLA-G1 via proteolytic cleavage in 221-G1-transfected cell line, in JEG3 cell line, and in peripheral blood mononuclear cells. The results obtained by both cell lines showed the role of MMP-2 in HLA-G1 shedding. On the contrary, MMP-9 was not involved in this process. In addition, we identified three possible highly specific cleavage sites for MMP-2, whereas none were detected for MMP-9. This study suggests an effective link between MMP-2 and HLA-G1 shedding, increasing our knowledge on the regulatory machinery beyond HLA-G regulation in physiological and pathological conditions.

  14. Phosphorylation status of 72 kDa MMP-2 determines its structure and activity in response to peroxynitrite.

    Directory of Open Access Journals (Sweden)

    Anna Laura Jacob-Ferreira

    Full Text Available Matrix metalloproteinase-2 (MMP-2 is a key intra- and extra-cellular protease which contributes to several oxidative stress related pathologies. A molecular understanding of 72 kDa MMP-2 activity, directly mediated by S-glutathiolation of its cysteine residues in the presence of peroxynitrite (ONOO(- and by phosphorylation of its serine and threonine residues, is essential to develop new generation inhibitors of intracellular MMP-2. Within its propeptide and collagen binding domains there is an interesting juxtaposition of predicted phosphorylation sites with nearby cysteine residues which form disulfide bonds. However, the combined effect of these two post-translational modifications on MMP-2 activity has not been studied. The activity of human recombinant 72 kDa MMP-2 (hrMMP-2 following in vitro treatments was measured by troponin I proteolysis assay and a kinetic activity assay using a fluorogenic peptide substrate. ONOO(- treatment in the presence of 30 µM glutathione resulted in concentration-dependent changes in MMP-2 activity, with 0.1-1 µM increasing up to twofold and 100 µM attenuating its activity. Dephosphorylation of MMP-2 with alkaline phosphatase markedly increased its activity by sevenfold, either with or without ONOO(-. Dephosphorylation of MMP-2 also affected the conformational structure of the enzyme as revealed by circular dichroism studies, suggesting an increase in the proportion of α-helices and a decrease in β-strands compared to the phosphorylated form of MMP-2. These results suggest that ONOO(- activation (at low µM and inactivation (at high µM of 72 kDa MMP-2, in the presence or absence of glutathione, is also influenced by its phosphorylation status. These insights into the role of post-translational modifications in the structure and activity of 72 kDa MMP-2 will aid in the development of inhibitors specifically targeting intracellular MMP-2.

  15. Detection and Significance of MMP-2 and CK19 on Lymph Node Micrometastases in Patients with Early Stage Cervical Cancer%MMP-2及CK19在早期宫颈癌淋巴结微转移中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    吉宏; 李莲英; 郭强; 任锦霞; 杨斌; 李晓琴

    2011-01-01

    目的:检测MMP-2和CK19在早期宫颈癌盆腔淋巴结中的表达,探讨淋巴结微转移的表达及意义.方法:采用免疫组化法对64例早期宫颈癌患者常规病理光镜检查证实无转移淋巴结902枚进行MMP-2及CK19的检测.结果:1)复发组477枚淋巴结中11枚CK19阳性(2.3%),来自32例患者中的8例(25.0%);8枚MMP-2阳性(1.7%),来自32例患者中的6例(18.8%),两种检测指标的结果有较好的一致性.未复发组425枚淋巴结中均无CK19及MMP-2阳性表达(0/425),该组32例患者中CK19及MMP-2的阳性表达率均为0.二者之间比较差异有统计学意义.2)CK19及MMP-2表达与病理类型及组织的分化程度均有相关性(P<0.05).3)复发组32例患者中带瘤生存25例,死亡7例,且均死于癌症,其中6例患者盆腔淋巴结中的CK-19及MMP-2检测均表达阳性,微转移与术后复发转移有相关性(P<0.05).结论:采用免疫组化技术检测淋巴结中CK19及MMP-2表达可检测出早期宫颈癌淋巴结中的微转移,显著提高微转移的检出率.通过本研究证实MMP-2及CK19的高表达与宫颈癌的侵袭转移有关,可作为检测早期宫颈癌淋巴转移的生物学指标之一,指导临床治疗.%Objective: To evaluate the significance of the matrix metalloproteinase-2 ( MMP-2 ) and cytokeratin 19 ( CK19 ) expressions in the pelvic lymph nodes of patients with early stage cervical cancer.Methods: Immunohistochemical staining and light microscopy were used to detect the expression of MMP-2 and CK19 in 902 lymph nodes from 64 patients.A routine pathological examination was performed to confirm lymph node metastasis.Results: In the relapse group, 11 of 477 patients had CK19-positive lymph nodes ( 2.3% ); from 8 of 32 patients ( 25% ), 8 were MMP-2 positive ( 1.7% ) from 32 patients in 6 ( 18.8% ), the results of the two test targets are in good agreement.In the group without recurrence, the 425 lymph nodes from 32 patients showed negative CK19 and MMP-2

  16. 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

  17. 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.

  18. An MMP-2 Responsive Liposome Integrating Antifibrosis and Chemotherapeutic Drugs for Enhanced Drug Perfusion and Efficacy in Pancreatic Cancer.

    Science.gov (United States)

    Ji, Tianjiao; Li, Suping; Zhang, Yinlong; Lang, Jiayan; Ding, Yanping; Zhao, Xiao; Zhao, Ruifang; Li, Yiye; Shi, Jian; Hao, Jihui; Zhao, Ying; Nie, Guangjun

    2016-02-10

    Fibrotic stroma, a critical character of pancreatic tumor microenvironment, provides a critical barrier against the penetration and efficacy of various antitumor drugs. Therefore, new strategies are urgently needed to alleviate the fibrotic mass and increase the drug perfusion within pancreatic cancer tissue. In our current work, we developed a β-cyclodextrin (β-CD) modified matrix metalloproteinase-2 (MMP-2) responsive liposome, integrating antifibrosis and chemotherapeutic drugs for regulation of pancreatic stellate cells (PSCs), a key source of the fibrosis, and targeted delivery of cytotoxic drugs for pancreatic cancer therapy. These liposomes disassembed into two functional parts upon MMP-2 cleavage at the tumor site. One part was constituted by the β-CDs and the antifibrosis drug pirfenidone, which was kept in the stroma and inhibited the expression of collagen I and TGF-β in PSCs, down-regulating the fibrosis and decreasing the stromal barrier. The other segment, the RGD peptide-modified-liposome loading the chemotherapeutic drug gemcitabine, targeted and killed pancreatic tumor cells. This integrated nanomedicine, showing an increased drug perfusion without any overt side effects, may provide a potential strategy for improvement of the pancreatic cancer therapy.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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

  3. Mycobacterium tuberculosis-infected human monocytes down-regulate microglial MMP-2 secretion in CNS tuberculosis via TNFα, NFκB, p38 and caspase 8 dependent pathways

    Directory of Open Access Journals (Sweden)

    Elkington Paul T

    2011-05-01

    Full Text Available Abstract Tuberculosis (TB of the central nervous system (CNS is a deadly disease characterized by extensive tissue destruction, driven by molecules such as Matrix Metalloproteinase-2 (MMP-2 which targets CNS-specific substrates. In a simplified cellular model of CNS TB, we demonstrated that conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb, but not direct infection, unexpectedly down-regulates constitutive microglial MMP-2 gene expression and secretion by 72.8% at 24 hours, sustained up to 96 hours (P M.tb-infected monocyte-dependent networks paradoxically involves the pro-inflammatory mediators TNF-α, p38 MAP kinase and NFκB in addition to a novel caspase 8-dependent pathway.

  4. Mechanical stretch induces MMP-2 release and activation in lung endothelium: role of EMMPRIN.

    Science.gov (United States)

    Haseneen, Nadia A; Vaday, Gayle G; Zucker, Stanley; Foda, Hussein D

    2003-03-01

    High-volume mechanical ventilation leads to ventilator-induced lung injury. This type of lung injury is accompanied by an increased release and activation of matrix metalloproteinases (MMPs). To investigate the mechanism leading to the increased MMP release, we systematically studied the effect of mechanical stretch on human microvascular endothelial cells isolated from the lung. We exposed cells grown on collagen 1 BioFlex plates to sinusoidal cyclic stretch at 0.5 Hz using the Flexercell system with 17-18% elongation of cells. After 4 days of cell stretching, conditioned media and cell lysate were collected and analyzed by gelatin, casein, and reverse zymograms as well as Western blotting. RT-PCR of mRNA extracted from stretched cells was performed. Our results show that 1) cyclic stretch led to increased release and activation of MMP-2 and MMP-1; 2) the activation of MMP-2 was accompanied by an increase in membrane type-1 MMP (MT1-MMP) and inhibited by a hydroxamic acid-derived inhibitor of MMPs (Prinomastat, AG3340); and 3) the MMP-2 release and activation were preceded by an increase in production of extracellular MMP inducer (EMMPRIN). These results suggest that cyclic mechanical stretch leads to MMP-2 activation through an MT1-MMP mechanism. EMMPRIN may play an important role in the release and activation of MMPs during lung injury.

  5. Thrombin stimulates VSMC proliferation through an EGFR-dependent pathway: involvement of MMP-2.

    Science.gov (United States)

    Smiljanic, Katarina; Obradovic, Milan; Jovanovic, Aleksandra; Djordjevic, Jelena; Dobutovic, Branislava; Jevremovic, Danimir; Marche, Pierre; Isenovic, Esma R

    2014-11-01

    In this study, the role of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK1/2), heparin-binding EGF-like growth factor (HB-EGF), general metalloproteinases, matrix metalloproteinases-2 (MMP-2) in mediating the mitogenic action of thrombin in rat vascular smooth muscle cells (VSMC) was investigated. The incubation of rat VSMC with thrombin (1 U/ml) for 5 min resulted in significant (p EGFR phosphorylation by 8.5 ± 1.3-fold (p EGFR tyrosine kinase irreversible inhibitor, 10 µM PD169540 (PD), and 20 µM anti-HB-EGF antibody significantly reduced thrombin-stimulated EGFR and ERK1/2 phosphorylation by 81, 72 % and by 48 and 61 %, respectively. Furthermore, the same pretreatments with PD or anti-HB-EGF antibody reduced thrombin-induced VSMC proliferation by 44 and 45 %, respectively. In addition, 30-min pretreatments with 10 µM specific MMP-2 inhibitor significantly reduced thrombin-stimulated phosphorylation of both EGFR and ERK1/2 by 25 %. Moreover, the same pretreatment with MMP-2 inhibitor reduced thrombin-induced VSMC proliferation by 45 %. These results show that the thrombin-induced DNA synthesis correlates with the level of ERK1/2 activation rather than EGFR activation. These results further suggest that thrombin acts through EGFR and ERK 1/2 signaling pathways involving MMP-2 to upregulate proliferation of VSMC.

  6. Molecular design of a highly selective and strong protein inhibitor against matrix metalloproteinase-2 (MMP-2).

    Science.gov (United States)

    Higashi, Shouichi; Hirose, Tomokazu; Takeuchi, Tomoka; Miyazaki, Kaoru

    2013-03-29

    Synthetic inhibitors of matrix metalloproteinases (MMPs), designed previously, as well as tissue inhibitors of metalloproteinases (TIMPs) lack enzyme selectivity, which has been a major obstacle for developing inhibitors into safe and effective MMP-targeted drugs. Here we designed a fusion protein named APP-IP-TIMP-2, in which the ten amino acid residue sequence of APP-derived MMP-2 selective inhibitory peptide (APP-IP) is added to the N terminus of TIMP-2. The APP-IP and TIMP-2 regions of the fusion protein are designed to interact with the active site and the hemopexin-like domain of MMP-2, respectively. The reactive site of the TIMP-2 region, which has broad specificity against MMPs, is blocked by the APP-IP adduct. The recombinant APP-IP-TIMP-2 showed strong inhibitory activity toward MMP-2 (Ki(app) = 0.68 pm), whereas its inhibitory activity toward MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, or MT1-MMP was six orders of magnitude or more weaker (IC50 > 1 μm). The fusion protein inhibited the activation of pro-MMP-2 in the concanavalin A-stimulated HT1080 cells, degradation of type IV collagen by the cells, and the migration of stimulated cells. Compared with the decapeptide APP-IP (t½ = 30 min), APP-IP-TIMP-2 (t½ ≫ 96 h) showed a much longer half-life in cultured tumor cells. Therefore, the fusion protein may be a useful tool to evaluate contributions of proteolytic activity of MMP-2 in various pathophysiological processes. It may also be developed as an effective anti-tumor drug with restricted side effects.

  7. 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.

  8. Inhibition of pro-/active MMP-2 by green tea catechins and prediction of their interaction by molecular docking studies.

    Science.gov (United States)

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

    2017-03-01

    Matrix metalloproteinases (MMPs) play a crucial role in developing different types of lung diseases, e.g., pulmonary arterial hypertension (PAH). Green tea polyphenolic catechins such as EGCG and ECG have been shown to ameliorate various types of diseases including PAH. Our present study revealed that among the four green tea catechins (EGCG, ECG, EC, and EGC), EGCG and ECG inhibit pro-/active MMP-2 activities in pulmonary artery smooth muscle cell (PASMC) culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-2 with the green tea catechins by computational methods. In silico analysis revealed a strong interaction of pro-/active MMP-2 with EGCG/ECG, and galloyl group has been observed to be responsible for this interaction. The in silico analysis corroborated our experimental observation that EGCG and ECG are active in preventing both the proMMP-2 and MMP-2 activities. Importantly, these two catechins appeared to be better inhibitors for proMMP-2 in comparison to MMP-2 as revealed by gelatin zymogram and also by molecular docking studies. In many type of cells, activation of proMMP-2 occurs via an increase in the level of MT1-MMP (MMP-14). We, therefore, determined the interactions of MT1-MMP with the green tea catechins by molecular docking analysis. The study revealed a strong interaction of MT1-MMP with EGCG/ECG, and galloyl group has been observed to be responsible for the interaction.

  9. Correlation of MMP-2 and TIMP-2 with Mesangial Proliferative Glomerulo-nephritis and Its Research Progress in Traditional Chinese Medicine%系膜增生性肾小球肾炎与MMP-2、TIMP-2的关系及中医药研究进展

    Institute of Scientific and Technical Information of China (English)

    胡营杰; 任现志

    2014-01-01

    Objective] To explore both the correlation of matrix metal oproteinase and the imbalance of its tissue inhibitors-MMP-2 and TIMP-2 with glomerulosclerosis and its research progress in traditional Chinese medicine. [Methods] We generalized the research progress in traditional Chinese medicine from such aspects as the biological properties of MMP-2 and TMIP-2 and their mechanisms, their relationship with mesangial proliferative glomerulonephritis and effects of traditional Chinese medicine on their expression by searching the relevant literatures. [Results] Expressions of MMP-2 and TIMP-2 vary in different pathological stages(hyperplasia and sclerosis stage here) of glomerulonephritis, and traditional Chinese herbs could adjust their expressions in different stages. Traditional Chinese herbs can inhibit the development of glomerulosclerosis. [Conclusion] Applying traditional Chinese medicine in the treatment of mesangialproliferative glomerulonephritis could provide the base for further development of TCM as wel as a new choice for treating mesangialproliferative glomerulonephritis.%[目的]探究基质金属蛋白酶及其组织抑制剂MMP-2、TIMP-2的失衡与肾小球的硬化的关系及中医药方面的研究进展。[方法]通过查阅相关文献,从MMP-2、TIMP-2的生物学特性及作用机制、与系膜增生性肾小球肾炎的关系、中医药对其表达的影响等方面加以论述,指出现阶段中医药研究方面的进展。[结果]MMP-2、TIMP-2在肾小球肾炎的疾病发展的不同病理阶段(本文主要阐述增生硬化阶段)的表达不同,中医药能够在不同的病理阶段上调或下调其表达,延缓疾病向肾小球硬化的进展。[结论]中医药在系膜增生性肾小球肾炎方向的应用为中医药的发展提供了依据,同时为系膜增生性肾小球肾炎的治疗提供新的方向。

  10. Differential actions of the endocytic collagen receptor uPARAP/Endo180 and the collagenase MMP-2 in bone homeostasis

    DEFF Research Database (Denmark)

    Madsen, Daniel H; Jürgensen, Henrik J; Ingvarsen, Signe;

    2013-01-01

    the extracellular collagenase, MMP-2, and the endocytic collagen receptor, uPARAP, by generating mice with combined deficiency of both components. In both uPARAP-deficient and MMP-2-deficient adult mice the length of the tibia and femur was decreased, along with a reduced bone mineral density and trabecular bone...... quality. An additional decrease in bone length was observed when combining the two deficiencies, pointing to both components being important for the remodeling processes in long bone growth. In agreement with results found by others, a different effect of MMP-2 deficiency was observed in the distinct bone...... structures of the calvaria. These membranous bones were found to be thickened in MMP-2-deficient mice, an effect likely to be related to an accompanying defect in the canalicular system. Surprisingly, both of the latter defects in MMP-2-deficient mice were counteracted by concurrent uPARAP deficiency...

  11. 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.

  12. Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish; Prause, Jan Ulrik; Nielsen, Boye Schnack;

    2008-01-01

    , -2, -9, and -13 mRNA expression by in situ hybridization with (35)S-radiolabeled riboprobes. Immunohistochemical studies of the same specimens were conducted with MMP-2-specific antibodies. For double-labeling experiments, primary MMP-2-specific antibodies and antibodies binding to fibroblasts...... and macrophages were used. RESULTS: MMP-2 mRNA expression was detected in 10 (91%) of 11 eyes with MASS and scleral tumor invasion. In eight (73%) of these cases, the expression signals were seen in numerous scleral fibroblasts. In melanoma cases without MASS, MMP-2 mRNA expression was detected in four (36......%) cases, and only one (9%) showed numerous positive cells. Tumor-infiltrating macrophages were found to harbor MMP-2, shown by a double-labeling experiment. The MMP-2 expression by immunostaining coincides with MMP-2 expression by in situ hybridization. No MMP-2 expression was detected in the tumor cells...

  13. The Inhibitory Effect of C-phycocyanin Containing Protein Extract (C-PC Extract) on Human Matrix Metalloproteinases (MMP-2 and MMP-9) in Hepatocellular Cancer Cell Line (HepG2).

    Science.gov (United States)

    Kunte, Mugdha; Desai, Krutika

    2017-03-30

    Spirulina platensis :have been studied for several biological activities. In the current study C-phycocyanin containing protein extract (C-PC extract) of Spirulina platensis have been studied for its effect on human matrix metalloproteinases (MMP-1, MMP-2 and MMP-9) and tissue inhibitors of MMPs (TIMP-1 and TIMP-2). In the present study, breast cancer cell line (MDA-MB 231) and hepatocellular cancer cell line (HepG2) were examined for inhibition of MMPs at different levels of expression after C-PC extract treatment. Herein, we have demonstrated that C-PC extract significantly reduced activity of MMP-2 by 55.13% and MMP-9 by 57.9% in HepG2 cells at 15 μg concentration. Additionally, the treatment has reduced mRNA expression of MMP-2 and MMP-9 at 20 μg concentration by 1.65-folds and 1.66-folds respectively. The C-PC extract treatment have also downregulated a mRNA expression of TIMP-2 by 1.12 folds at 20 μg concentration in HepG2 cells. Together, these results indicate that C-PC, extract successfully inhibited MMP-2 and -9 at different levels of expression and TIMP-2 at a mRNA expression level; however, extract did not have any effect on MMP-1 expressed in MDA-MB231 and TIMP-1 expressed in HepG2 cells as well as the exact mechanism of inhibition of MMP-2, MMP-9 and TIMP-2 remained unclear.

  14. ERK1/2 and p38 MAP kinase control MMP-2, MT1-MMP, and TIMP action and affect cell migration : a comparison between mesothelioma and mesothelial cells

    NARCIS (Netherlands)

    Zhong, Jun; Gencay, Mikael M Cornelsen; Bubendorf, Lukas; Burgess, Janette K; Parson, Holly; Robinson, Bruce W S; Tamm, Michael; Black, Judith L; Roth, Michael

    2006-01-01

    Pleural malignant mesothelioma is a locally aggressive tumor of mesothelial cell origin. In other tumor types high expression of matrix metalloproteinase (MMP)-2, together with membrane-type1-MMP (MT1-MMP), and low levels of the tissue inhibitor of MMP (TIMP)-2 have been correlated with aggressive t

  15. Toxicity reduction and MMP-2 stimulation of papain and bromelain loaded in elastic niosomes.

    Science.gov (United States)

    Manosroi, Aranya; Chankhampan, Charinya; Manosroi, Worapaka; Manosroi, Jiradej

    2012-10-01

    The elastic niosomes (Tween 61/cholesterol/sodium cholate at 1:1:0.1 molar ratio) loaded with the protease enzymes (papain and bromelain) gave the vesicular sizes of 109.5 to 143.9 nm with the negative zeta potential of -14.7 to -30.1 mv. The elastic niosomes loaded with the standard papain (PS), extracted papain (PE), standard bromelain (BS) and extracted bromelain (BE) showed deformability index (DI values) of 1.35, 1.81, 1.22 and 1.61 times higher than their corresponding non-elastic niosomes, respectively. The elastic niosomes did not only improve the entrapment efficiency of the enzymes over the non-elastic niosomes of about 1.35 times, but also reduced the toxicity on skin human fibroblasts by SRB assay of the PS, PE, BS and BE at 1.68, 2.10, 1.56 and 1.52 times, respectively. The relative MMP-2 stimulation of PS, PE, BS and BE loaded in elastic niosomes were 1.26 +/- 0.14, 1.34 +/- 0.15, 1.09 +/- 0.09 and 1.20 +/- 0.04 for the pro MMP-2 and 1.26 +/- 0.12, 1.41 +/- 0.23, 1.01 +/- 0.08 and 1.03 +/- 0.12 for the active MMP-2, respectively in comparing to the control which were similar activity to their free enzymes. The PE loaded in elastic niosomes gave superior characteristics (low cytotoxicity and high MMP-2 stimulation) to other enzymes. The elastic niosomes can enhance the chemical stability of PE, which exhibited higher remaining contents than the free PE of 1.36 times when kept at 27 +/- 2 degrees C after 8 weeks. Therefore, the extracted papain loaded in elastic niosomes appeared to have potential to be developed as a topical product for scar treatment.

  16. Alendronate inhibits cell invasion and MMP-2 secretion in human chondrosarcoma cell line

    Institute of Scientific and Technical Information of China (English)

    Te-jen LAI; Yi-chin FONG; Sheng-feng HSU; Temao LI; Horng-chaung HSU; Jaung-geng LIN; Chin-jung HSU; Ming-chih CHOU; Meng-chih LEE; Shun-fa YANG

    2007-01-01

    Aim: Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. The aim of the present study was to investigate the effect of alendronate, a bisphosphonate, on the invasion and migration of human chondrosarcoma cells (JJ012). Methods: JJ012 cells were treated with alendronate of various concentrations up to 100 μmol/L for a speci-fied period, and then gelatin zymography and matrigel invasion assay was per-formed to study the effects of alendronate on matrix metalloproteinase (MMP)-2 activity and the invasion ability of JJ012 cells, respectively. Results: Our data showed that alendronate exerted a dose- and time-dependent inhibitory effect on the invasion and migration of JJ012 cells. Furthermore, gelatin zymography and RT-PCR showed that alendronate treatment decreased the activity and mRNA levels of MMP-2 in a concentration-dependent manner. Conclusion: Our find-ings suggest that alendronate may reduce MMP-2 secretion at the transcriptional and translational levels, and inhibit the invasion of chondrosarcoma cell. Therefore,alendronate may be a potential candidate for the systemic therapy of chondro-sarcomas, as well as other malignant diseases.

  17. 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.

  18. Effect of piperine combined with cisplation on proliferation and MMP-2, VEGF of human lung adenocarcinoma A549 cell%胡椒碱联合顺铂对肺腺癌 A549 细胞生长及 MMP-2、VEGF 的影响

    Institute of Scientific and Technical Information of China (English)

    何含含; 岳红梅; 鲁文强; 罗亚娟

    2015-01-01

    目的:研究胡椒碱与顺铂联合对肺腺癌A549细胞生长和凋亡的作用,以及检测A549细胞基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达水平. 方法:MTT法检测不同质量浓度的胡椒碱、顺铂及两者联合对A549细胞增殖的影响. 流式细胞术分析细胞凋亡. RT-PCR测定各组A549细胞MMP-2 mRNA和VEGF mRNA的表达变化. 结果:胡椒碱与顺铂均可抑制人肺腺癌A549细胞的生长,呈时间—浓度依赖性( P<0.05 );联合组随作用时间延长,对A549细胞的抑制效应增加( P<0.05 ). 联合组较对照组、胡椒碱组、顺铂组的A549细胞凋亡率显著增高( P<0.05 ). 联合组与对照组及单用胡椒碱、顺铂比较, MMP-2 mRNA和VEGF mRNA 的表达明显下调( P<0.05 ). 结论:胡椒碱显著提高顺铂对肺腺癌A549细胞的生长抑制和促进凋亡效应,降低MMP-2、VEGF的表达,从而可能抑制肺癌细胞的迁移.%Objective:To investigate the proliferation and apoptosis of piperine combined with cisplation on A 549 cells and the changes in the expression of MMP-2 and VEGF.Methods: MTT assay was used to detect the proliferation on A549 cells after treatment with series of monotherapy group ( piperine or cisplation alone ) or combination group ( piperine combined with cisplation ) .Flow cytometry was performed to assess the cellular apoptosis.The expression of MMP-2,VEGF mRNA were measured by RT-PCR in each group.Results: Both piperine and cisplation could inhibit the growth of A 549 cells in a time-dose dependent manner ( P<0.05 ) .With the increasing time , the cell proliferation was significantly inhibited in the combination group ( P <0.05 ) .The combination group also showed an obviously higher apoptosis rate than piperine alone , cisplation alone and control group, respectively( P<0.05).In addition, the expression of MMP-2 and VEGF mRNA in combination group were evidently lower than

  19. MMP-2 -1575G/A polymorphism modifies the onset of optic neuritis as a first presenting symptom in MS?

    Science.gov (United States)

    Gašparović, Iva; Čizmarević, Nada Starčević; Lovrečić, Luca; Perković, Olivio; Lavtar, Polona; Sepčić, Juraj; Jazbec, Saša Šega; Kapović, Miljenko; Peterlin, Borut; Ristić, Smiljana

    2015-09-15

    Previous studies show altered activities of matrix metalloproteinase (MMP)-2 and MMP-9 in serum and cerebrospinal fluid of multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. Optic neuritis (ON) is a common symptom of both disorders. Here we investigated the impacts of MMP-2 -1575G/A and MMP-9 -1562 C/T gene polymorphisms on disease phenotype in 100 MS patients with ON as a first symptom and 376 MS patients with other initial symptomatology. The MMP-2 -1575G/A polymorphism led to a 5-year-earlier age of disease onset in MS patients with ON as a first symptom (p=0.009).

  20. 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

  1. Sphingosine-1-phosphate induces human endothelial VEGF and MMP-2 production via transcription factor ZNF580: Novel insights into angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Hui-Yan, E-mail: shy35309@sohu.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Wei, Shu-Ping, E-mail: weishuping_83@163.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Xu, Rui-Cheng, E-mail: xu_rc@sohu.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Xu, Peng-Xiao, E-mail: xupengxiao1228@sina.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Zhang, Wen-Cheng, E-mail: wenchengzhang@yahoo.com [Department of Physiology and Pathophysiology, Medical College of Chinese People' s Armed Police Forces, Tianjin 300162 (China)

    2010-05-07

    Sphingosine-1-phosphate (S1P)-induced migration and proliferation of endothelial cells are critical for angiogenesis. C2H2-zinc finger (ZNF) proteins usually play an essential role in altering gene expression and regulating the angiogenesis. The aim of this study is to investigate whether a novel human C2H2-zinc finger gene ZNF580 (Gene ID: 51157) is involved in the migration and proliferation of endothelial cells stimulated by S1P. Our study shows that EAhy926 endothelial cells express S1P1, S1P3 and S1P5 receptors. Furthermore, S1P upregulates both ZNF580 mRNA and protein levels in a concentration- and time-dependent manner. SB203580, the specific inhibitor of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, blocks the S1P-induced upregulation of ZNF580. Moreover, overexpression/downexpression of ZNF580 in EAhy926 cells leads to the enhancement/decrease of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) expression as well as the migration and proliferation of EAhy926 endothelial cells. These results elucidate the important role that ZNF580 plays in the process of migration and proliferation of endothelial cells, which provides a foundation for a novel approach to regulate angiogenesis.

  2. Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy

    DEFF Research Database (Denmark)

    Sun, S; Henriksen, K; Karsdal, M A;

    2014-01-01

    used to assess biological and clinical relevance. RESULTS: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy...... model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up...... at a 16.4 (±4.6) % increase at day 47. CONCLUSIONS: We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy....

  3. Clinical significance of serum levels of matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in gastric cancer.

    Science.gov (United States)

    Mroczko, Barbara; Lukaszewicz-Zając, Marta; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

    2011-01-01

    Matrix metalloproteinase 2 (MMP-2) is able to degrade type IV collagen, and thus plays a key role in the migration of tumor cells. MMP-2 activity is inhibited by its tissue inhibitor (TIMP-2). The imbalance between MMPs and TIMPs may facilitate progression of cancer cells. The aim of this study was to compare the clinical importance of MMP-2 and TIMP-2 to that of classical tumor markers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in the diagnosis of gastric cancer (GC) by calculating the diagnostic criteria and estimating the levels of MMP-2, TIMP-2, CEA and CA 19-9 in GC patients in relation to clinicopathological features of cancer. We found that serum levels of MMP-2 and TIMP-2 were significantly lower, whereas serum tumor markers were higher, in GC patients than in healthy subjects. Moreover, concentrations of TIMP-2 and CEA correlated with gastric wall infiltration, while CA 19-9 levels correlated with gastric wall infiltration and the presence of nodal metastasis. None of the proteins tested was found to be an independent prognostic factor for GC patients' survival. The percentage of true positive results of TIMP-2 (61%) was higher than those of MMP-2 (54%) and the classical tumor markers CEA (21%) and CA 19-9 (31%). The highest diagnostic sensitivity was observed for the combined use of TIMP-2 with MMP-2 (77%). The results suggest the greater importance of serum MMP-2 and TIMP-2 than of the classical tumor markers CEA and CA 19-9 in the diagnosis of GC. But this issue requires further investigation.

  4. Therapy of psoriasis with narrowband ultraviolet-B light influences plasma concentrations of MMP-2 and TIMP-2 in patients

    Directory of Open Access Journals (Sweden)

    Głażewska EK

    2016-10-01

    Full Text Available Edyta Katarzyna Głażewska,1 Marek Niczyporuk,1 Sławomir Ławicki,2 Maciej Szmitkowski,2 Monika Zajkowska,2 Grażyna Ewa Będkowska,3 Andrzej Przylipiak1 1Department of Esthetic Medicine, 2Department of Biochemical Diagnostics, 3Department of Haematological Diagnostics, Medical University, Białystok, Poland Background: Matrix metalloproteinases (MMPs, which show a significant ability to cleave the components of extracellular matrix, and tissue inhibitors of metalloproteinases (TIMPs, which slow down the activity of those enzymes, may be implicated in the pathogenesis and spread of psoriatic disease. This study aims to analyze plasma levels of MMP-2 and TIMP-2 in plaque psoriasis patients before and after the course of narrowband ultraviolet-B (NBUVB therapy with respect to disease advancement. Patients and methods: A total of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were enrolled into the study. Plasma levels of MMP-2 and TIMP-2 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index (PASI was used to define the disease advancement. Results: The results showed increased plasma levels of MMP-2 and TIMP-2, but this change was significant only in case of MMP-2 in total psoriatic group compared to healthy subjects. Moreover, there was an increase in the concentrations of chosen factors with an increase in the severity of the disease. The NBUVB therapy causes a decline in the concentration of the analyzed enzyme and its inhibitor, although this change was statistically significant in the total psoriatic group only in case of MMP-2. There was also a positive correlation between MMP-2, TIMP-2, and PASI score value. Conclusion: Our study highlights a possible important role of MMP-2 in the activity of psoriasis and clearance of disease symptoms. Moreover, plasma MMP-2 seems to be a valuable psoriasis biomarker. Keywords: gelatinase A, matrix metalloproteinases, tissue inhibitor of

  5. Transcription activity of MMP-2 and MMP-9 metalloproteinase genes and their tissue inhibitor (TIMP-2 in acute coronary syndrome patients

    Directory of Open Access Journals (Sweden)

    J Dabek

    2013-01-01

    Full Text Available Background: Acute coronary syndromes (ACS are a consequence of coronary vessel atherosclerosis and they are a leading cause of death in industrialized countries. One of the ACS causative factors is the deranged ratio equilibrium of the matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMPs/TIMPs. Aims: Assessment of transcriptional activity of metalloproteinase genes using Human Genome-U133A oligonucleotide microarrays and selection of candidate genes differentiating ACS patients from healthy subjects and finally, QRT-PCR (quantitative real time polymerase chain reaction confirmation of the results. Settings and Design: The study involved 67 ACS patients, admitted on a consecutive basis, to the Cardiology Clinic as well as 24 healthy subjects (control. Materials and Methods: Ribonucleic acid isolated from peripheral blood mononuclear cells was analyzed by QRT-PCR. Transcriptional activity of the analyzed gene was assessed with TaqMan gene expression assays. Statistical Analysis: U Mann-Whitney test was used to compare the results. Results: Homogeneity of the investigated group was assessed through hierarchical clusterization whereas the nine genes differentiating ACS patients from healthy persons were selected using the Bland-Altman technique. Among these genes three (platelet derived growth factor D, NUAK family SNF1-like kinase 1 and peroxisomal biogenesis factor 1 showed decreased transcriptional activity whereas the remaining six genes (MMP-2 and MMP-9, CDK5RAP3, transmembrane BAX inhibitor motif containing 1, adenylate cyclase-associated protein 1 and TIMP-2 were increased. MMP-2, MMP-9 and TIMP-2 were further characterized by QRT-PCR. Conclusions: The obtained results permit to conclude that the increased expression of MMP-2 and MMP-9 metalloproteinases and their tissue inhibitor (TIMP-2 is responsible for disturbed equilibrium of the metalloproteinase/tissue inhibitors system and as a consequence, for destabilization of

  6. Inhibition of MMP-2-mediated cellular invasion by NF-κB inhibitor DHMEQ in 3D culture of breast carcinoma MDA-MB-231 cells: A model for early phase of metastasis.

    Science.gov (United States)

    Ukaji, Tamami; Lin, Yinzhi; Okada, Shoshiro; Umezawa, Kazuo

    2017-02-08

    The three-dimensional (3D) culture of cancer cells provides an environmental condition closely related to the condition in vivo. It would especially be an ideal model for the early phase of metastasis, including the detachment and invasion of cancer cells from the primary tumor. In one hand, dehydroxymethylepoxyquinomicin (DHMEQ), an NF-κB inhibitor, is known to inhibit cancer progression and late phase metastasis in animal experiments. In the present research, we studied the inhibitory activity on the 3D invasion of breast carcinoma cells. Breast carcinoma MDA-MB-231 cells showed the most active invasion from spheroid among the cell lines tested. DHMEQ inhibited the 3D invasion of cells at the 3D-nontoxic concentrations. The PCR array analysis using RNA isolated from the 3D on-top cultured cells indicated that matrix metalloproteinase (MMP)-2 expression is lowered by DHMEQ. Knockdown of MMP-2 and an MMP inhibitor, GM6001, both inhibited the invasion. DHMEQ was shown to inhibit the promoter activity of MMP-2 in the reporter assay. Thus, DHMEQ was shown to inhibit NF-κB/MMP-2-dependent cellular invasion in 3D-cultured MDA-MB-231 cells, suggesting that DHMEQ would inhibit the early phase of metastasis.

  7. 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.

  8. Induced Neural Differentiation of MMP-2 Cleaved (RADA)4 Drug Delivery Systems.

    Science.gov (United States)

    Koss, K; Tsui, C; Unsworth, L D

    2016-12-10

    (RADA)4 self-assembling peptides (SAPs) are promising for neural nanoscaffolds with on-demand drug delivery capabilities due to their automated synthesis, in-situ assembly, and potential for interaction with and release of biomolecules. Neuroinflammation cued on-demand drug release, due to up-regulated proteases, may well be vital in the treatment of several neurological diseases. In these conditions, releasing neurotrophic growth factors (NTFs) could potentially lead to neuroprotection and neurogenesis. As such, (RADA)4 was made with the high and low activity matrix metalloproteinase 2 (MMP-2) cleaved sequences, GPQG+IASQ (CP1) and GPQG+PAGQ (CP2), the brain-derived NTF secretion stimulating peptide MVG (DP1) and the ciliary NTF analogue DGGL (DP2). PC-12 cell culture was performed to assess bioactive substrate cell adhesion and NTF specific neuronal differentiation. The laminin-derived IKVAV peptide, known for neural cell attachment and interaction, was tethered to (RADA)4-IKVAV and mixed in increasing increments with (RADA)4 for this purpose. With 1 nanomolar MMP-2 treatment, product formation was observed to increase over a three day period, with (RADA)4/(RADA)4-CP1/CP2 mixture, however there was little difference between groups. Smaller CP1/CP2 concentrations displayed comparable (RADA)4 nanoscale morphology to higher concentrations. Acetylcholine esterase and neural differentiation was observed over 3 days with 1 nM MMP-2 treatment according to the following makeup: 8/1/1 (RADA)4/(RADA)4-IKVAV/(RADA)4-CP1/CP2-DP1/DP2. Signalling gradually increased in all groups, and neurite outgrowth was visible after three days.

  9. Raman spectroscopy for assessment of bone quality in MMP-2 knockout mice

    Science.gov (United States)

    Bi, Xiaohong; Nyman, Jeffry S.; Patil, Chetan A.; Masui, Philip; Lynch, Conor; Mahadevan-Jansen, Anita

    2009-02-01

    Knocking out a gene in mice provide the means to investigate potential regulators of the compositional, structural, and biomechanical properties of bone. Suppressing genes related to matrix turnover (bone remodeling) can have a significant effect on properties related to overall bone quality, which are normally measured using tests such as micro-computed tomography (μ-CT) and three point-bending to determine the structural and mechanical properties, respectively. Although Raman spectroscopy is known to non-destructively characterize biochemical properties of bone such as degree of mineralization and crystallinity, the correlation between these measurements and those of overall bone quality has not yet been systematically investigated. In this study we present a comparison of structural and mechanical properties of bone from mice deficient in matrix metalloproteinase 2 (MMP2) to compositional properties measured with RS. Femora were collected from MMP2+/+ and MMP2-/- mice at 16 weeks of age. Multiple Raman spectra were collected from the mid-diaphysis of intact femora in order to measure the bone's average compositional properties. In addition, μ-CT was used to characterize the structure and bone mineral density (BMD) at the mid-diaphysis, and three-point bending assessed the biomechanical properties of the same bones. Raman derived measurements of mineralization (ratio of Phosphate ν1 to CH2 bending), mineral crystallinity, collagen and mineral contents were significantly lower in the MMP null mice and demonstrated correlation with volumetric BMD, bending strength and modulus. In addition, all these measurements were shown to inversely correlate with post-yield-deflection (p<0.01). These results indicate the potential for RS to qualitatively assess bone quality.

  10. Intracellular matrix metalloproteinase-2 (MMP-2) regulates human platelet activation via hydrolysis of talin.

    Science.gov (United States)

    Soslau, Gerald; Mason, Christopher; Lynch, Stephen; Benjamin, James; Ashak, Dani; Prakash, Jamunabai M; Moore, Andrew; Bagsiyao, Pamela; Albert, Trevine; Mathew, Lynn M; Jost, Monika

    2014-01-01

    Matrix metalloproteinase (MMP) activity is generally associated with normal or pathological extracellular processes such as tissue remodelling in growth and development or in tumor metastasis and angiogenesis. Platelets contain at least three MMPs, 1, 2 and 9 that have been reported to stimulate or inhibit agonist-induced platelet aggregation via extracellular signals. The non-selective Zn+2 chelating MMP inhibitor, 1,10-phenanthroline, and the serine protease inhibitor, AEBSF, were found to inhibit all tested agonist-induced platelet aggregation reactions. In vitro analysis demonstrated that 1,10-phenanthroline completely inhibited MMP-1,2,and 9 but had little to no effect on calpain activity while the converse was true with AEBSF. We now demonstrate that MMP-2 functions intracellularly to regulate agonist-induced platelet aggregations via the hydrolytic activation of talin, the presumed final activating factor of glycoprotein (GP)IIb/IIIa integrin (the inside-out signal). Once activated GPIIb/IIIa binds the dimeric fibrinogen molecule required for platelet aggregation. The active intracellular MMP-2 molecule is complexed with JAK 2/STAT 3, as demonstrated by the fact that all three proteins are co-immunoprecipitated with either anti-JAK 2, or anti-STAT 3 antibodies and by immunofluorescence studies. The MMP-2 platelet activation pathway can be synergistically inhibited with the non-selective MMP inhibitor, 1,10-phenanthroline, plus a JAK 2 inhibitor. This activation pathway is distinct from the previously reported calpain-talin activating pathway. The identification of a new central pathway for platelet aggregation presents new potential targets for drug regulation and furthers our understanding of the complexity of platelet activation mechanisms.

  11. 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

  12. Type II VLDLR promotes cell migration by up-regulation of VEGF, MMP2 and MMP7 in breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Lei He; Yanjun Lu; Jianli Guo

    2013-01-01

    Objective:Very low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cel ular signaling. Our group previously reported that type II VLDLR overexpression in breast cancer tissues. The purpose of this study is to characterize type II VLDLR activities during cel migration using breast cancer cel lines. Methods:Western blotting was used to test protein expression. Cel migration was analyzed by Scratch wound assay. The mRNA expression was tested by realtime-PCR. Reporter assay was to test the transcription activity. Results:Scratch wound and Report assay indicated up-regulated VLDLR II expression promotes cel migration via activating Wnt/β-catenin pathway. The target genes such as VEGF, MMP2 and MMP7 were upregulated in VLDLR II overexpressed cel s. On the contrary, cel s treated with TFPI had an inhibition ef ect of cel migration response to down-regulation of VLDLR II. Conclusion:Type II VLDLR conferred a migration and invasion advantage by activating Wnt/β-catenin pathway, then up-regulating VEGF, MMP2 and MMP7 in breast cancer cel s.

  13. Inonotus obliquus-derived polysaccharide inhibits the migration and invasion of human non-small cell lung carcinoma cells via suppression of MMP-2 and MMP-9.

    Science.gov (United States)

    Lee, Ki Rim; Lee, Jong Seok; Song, Jeong Eun; Ha, Suk Jin; Hong, Eock Kee

    2014-12-01

    Polysaccharides isolated from the fruiting body of Inonotus obliquus (PFIO) are known to possess various pharmacological properties including antitumor activity. However, the anti-metastatic effect and its underlying mechanistic signaling pathway involved these polysaccharides in human non-small cell lung carcinoma remain unknown. The present study therefore aimed to determine the anti-metastatic potential and signaling pathways of PFIO in the highly metastatic A549 cells. We found that PFIO suppressed the migration and invasive ability of A549 cells while decreasing the expression levels and activity of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PFIO decreased the phosphorylation levels of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) as well as the expression level of COX-2, and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in A549 cells. These results suggested that PFIO could suppress the invasion and migration of human lung carcinoma by reducing the expression levels and activity of MMP-2 and MMP-9 via suppression of MAPKs, PI3K/AKT, and NF-κB signaling pathways.

  14. VEGF、MMP-2和MMP-9检测在子宫内膜异位症诊断中的应用价值%Application value of testing VEGF, MMP-2 and MMP-9 in the diagnosis of endometriosis

    Institute of Scientific and Technical Information of China (English)

    朱锋; 彭启松; 居蓉

    2016-01-01

    group were significantly higher than those of the non-EMs group, and the concentrations were signifi-cantly higher in EMs patients ofⅢ~Ⅳstage than those in EMs patients ofⅠ~Ⅱstage and non-EMs group (P<0.01), and also in EMs patients ofⅠ~Ⅱstage than those in non-EMs group (P<0.01). Conclusion The higher expression of VEGF, MMP-2 and MMP-9 in serum and peritoneal fluid in EMs patients suggested that they were associated with the occur-rence and development of EMs. Detecting the concentrations can be helpful for the diagnosis and stage evaluation.

  15. Effects of Rock2 Regulating MMP2 on Invasion and Metastasis in Hepatocellular Carcinoma%原发性肝癌细胞中Rock2调控MMP2对其侵袭迁移的作用

    Institute of Scientific and Technical Information of China (English)

    陈磊峰; 刘天德; 杜晓红; 胡俊文; 黄子曦; 邵江华

    2014-01-01

    目的 探讨Rho相关卷曲螺旋形成蛋白激酶2(Rho associated coiled coil containing protein kinase 2,Rock2)调控基质金属蛋白酶2(matrix metalloproteinase 2,MMP2)对肝癌细胞侵袭迁移能力的影响.方法 用Western blot法检测30例肝癌组织及对应癌旁组织中Rock2和MMP2的蛋白表达,同时分析它们之间的关联;用荧光定量PCR和Western blot法观察稳定降低Rock2细胞中MMP2 mRNA及蛋白表达变化;利用PCR定点突变技术构建Rock2同义突变质粒“恢复”稳定干扰Rock2的肝癌细胞中Rock2表达后检测MMP2蛋白表达变化;采用Transwell侵袭实验和划痕实验观察空白对照组、稳定低表达Rock2组、“恢复”Rock2组HepG2细胞侵袭和迁移能力变化.结果 Rock2和MMP2蛋白在肝癌组织中均比对应癌旁组织明显增高,且两者的表达呈正相关性.稳定降低肝癌细胞中Rock2的表达后发现MMP2的mRNA和蛋白表达也随之降低;另外,“恢复”稳定干扰Rock2的肝癌细胞中Rock2的表达,MMP2表达也“恢复”;同时证实Rock2通过调节MMP2表达从而影响肝癌细胞的侵袭和迁移.结论 在原发性肝癌细胞中降低Rock2可引起MMP2表达下降,进而抑制肝癌细胞的侵袭和迁移.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. Deep sea water prevents balloon angioplasty-induced hyperplasia through MMP-2: an in vitro and in vivo study.

    Directory of Open Access Journals (Sweden)

    Pei-Chuan Li

    Full Text Available Major facts about the development of restenosis include vascular smooth muscle cells (VSMCs proliferation and migration. A previous study showed that in vitro treatment with magnesium chloride has the potential to affect the proliferation and migration of VSMCs. Magnesium is the major element in deep sea water (DSW and is a biologically active mineral. It is unclear whether DSW intake can prevent abnormal proliferation and migration of VSMCs as well as balloon angioplasty-induced neointimal hyperplasia. Thus, we attempted to evaluate the anti-restenotic effects of DSW and its possible molecular mechanisms. Several concentrations of DSW, based on the dietary recommendations (RDA for magnesium, were applied to a model of balloon angioplasty in SD rats. The results showed that DSW intake markedly increased magnesium content within the vascular wall and reduced the development of neointimal hyperplasia. The immunohistochemical analysis also showed that the expression of proteins associated with cell proliferation and migration were decreased in the balloon angioplasty groups with DSW supplement. Furthermore, in vitro treatment with DSW has a dose-dependent inhibitory effect on serum-stimulated proliferation and migration of VSMCs, whose effects might be mediated by modulation of mitogen-activated protein kinase (MAPK signaling and of the activity of matrix metalloproteinase-2 (MMP-2. Our study suggested that DSW intake can help prevent neointimal hyperplasia (or restenosis, whose effects may be partially regulated by magnesium and other minerals.

  19. Deep sea water prevents balloon angioplasty-induced hyperplasia through MMP-2: an in vitro and in vivo study.

    Science.gov (United States)

    Li, Pei-Chuan; Pan, Chun-Hsu; Sheu, Ming-Jyh; Wu, Chin-Ching; Ma, Wei-Fen; Wu, Chieh-Hsi

    2014-01-01

    Major facts about the development of restenosis include vascular smooth muscle cells (VSMCs) proliferation and migration. A previous study showed that in vitro treatment with magnesium chloride has the potential to affect the proliferation and migration of VSMCs. Magnesium is the major element in deep sea water (DSW) and is a biologically active mineral. It is unclear whether DSW intake can prevent abnormal proliferation and migration of VSMCs as well as balloon angioplasty-induced neointimal hyperplasia. Thus, we attempted to evaluate the anti-restenotic effects of DSW and its possible molecular mechanisms. Several concentrations of DSW, based on the dietary recommendations (RDA) for magnesium, were applied to a model of balloon angioplasty in SD rats. The results showed that DSW intake markedly increased magnesium content within the vascular wall and reduced the development of neointimal hyperplasia. The immunohistochemical analysis also showed that the expression of proteins associated with cell proliferation and migration were decreased in the balloon angioplasty groups with DSW supplement. Furthermore, in vitro treatment with DSW has a dose-dependent inhibitory effect on serum-stimulated proliferation and migration of VSMCs, whose effects might be mediated by modulation of mitogen-activated protein kinase (MAPK) signaling and of the activity of matrix metalloproteinase-2 (MMP-2). Our study suggested that DSW intake can help prevent neointimal hyperplasia (or restenosis), whose effects may be partially regulated by magnesium and other minerals.

  20. Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy

    Science.gov (United States)

    Bae, Sun Sik; Lee, Min Young; Rhee, Harin; Kim, Il Young; Seong, Eun Young; Lee, Dong Won; Lee, Soo Bong; Kwak, Ihm Soo; Lovett, David H.

    2017-01-01

    Background We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms. Methods We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE) and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). The streptozotocin (STZ) murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study. Results Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold). Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively). Conclusions The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for

  1. Prognostic significance of TIMP-2, MMP-2, and MMP-9 on high-grade serous ovarian carcinoma using digital image analysis.

    Science.gov (United States)

    Desmeules, Patrice; Trudel, Dominique; Turcotte, Stéphane; Sirois, Jennifer; Plante, Marie; Grégoire, Jean; Renaud, Marie-Claude; Orain, Michèle; Têtu, Bernard; Bairati, Isabelle

    2015-05-01

    The objective of this cohort study was to evaluate whether the immunohistochemical expression of tissue inhibitor of metalloprotease 2, matrix metalloproteinase (MMP) 2, and MMP-9 could predict the occurrence of death and progression in women with ovarian high-grade serous carcinoma (HGSC). A total of 100 women with primary HGSC who were treated by cytoreductive surgery and adjuvant chemotherapy at the Centre Hospitalier Universitaire de Québec (Canada) were included. Biomarker expression was evaluated by immunohistochemistry on tissue microarrays constructed from primary tumors. Immunostaining quantification was performed using digital image analysis, from algorithms created with Calopix software, and continuous H-score data were obtained. The cancer antigen-125 and/or the Response Evaluation Criteria In Solid Tumors criteria were used to define progression. Dates of death were obtained by record linkage with the Québec mortality files. Hazard ratios (HRs) of death and progression with their 95% confidence intervals (CIs) were estimated using the Cox proportional hazards regression model. Overall, a low variability of expression was observed for each marker. No association was found between the level of expression and standard prognostic factors. When assessed as a continuous variable, increased MMP-9 expression (10 units of H-score) was associated with death (HR, 1.08; 95% CI, 1.01-1.16; P = .02), but not with progression (HR, 1.03; 95% CI, 0.97-1.10; P = .29). There was no association between the expression of MMP-2 or tissue inhibitor of metalloprotease 2 and death or progression. In conclusion, in a homogeneous cohort of women with HGSC, increased MMP-9 tissue expression, as assessed by automated immunostaining quantification, was associated with a higher risk of death.

  2. Quantum dots based molecular beacons for in vitro and in vivo detection of MMP-2 on tumor.

    Science.gov (United States)

    Li, Xin; Deng, Dawei; Xue, Jianpeng; Qu, Lingzhi; Achilefu, Samuel; Gu, Yueqing

    2014-11-15

    Matrix metalloproteinase-2 (MMP-2) is a protease related to tumor invasion and metastasis. It is heavily secreted by malignant tumor cells, allowing the protease to serve as an imaging biomarker of cancer. In this study, a novel sensing system based on fluorescence resonance energy transfer (FRET) from quantum dot (QD, the donor) to organic dye (the acceptor) was constructed for the in vitro and in vivo detection of matrix metalloproteinases-2 via a MMP-2-specific peptide substrate (GPLGVRGKGG). Specifically, 535 nm-emitting CdTe QD were bound to Rhodamine B (RB) through the peptide for in vitro detection of MMP-2, while 720 nm-emitting CdTeS QDs was linked to near infrared dye ICG-Der-02 (MPA) by the peptide for measurement in vivo. When these probes were exposed to MMP-2, the selective cleavage of the peptide resulted in the recovery of fluorescence from QDs. By using the produced 540QD-peptide-RB and 720QD-peptide-MPA probes, we successfully examined MMP-2 in live cells and tumor on nude mouse, respectively. Due to the tunable fluorescence of Qds, this nanosensor can be fine-tuned for a wide range of applications such as the detection of different biomarkers and early diagnosis of disease.

  3. Elevated STAT3 Signaling-Mediated Upregulation of MMP-2/9 Confers Enhanced Invasion Ability in Multidrug-Resistant Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Fei Zhang

    2015-10-01

    Full Text Available The development of multidrug resistance greatly impedes effective cancer therapy. Recent advances in cancer research have demonstrated that acquisition of multidrug resistance by cancer cells is usually accompanied by enhanced cell invasiveness. Several lines of evidence indicated that cross activation of other signaling pathways during development of drug resistance may increase invasive potential of multidrug-resistant (MDR cancer cells. However, the accurate mechanism of this process is largely undefined. In this study, to better understand the associated molecular pathways responsible for cancer progression induced by drug resistance, a MDR human breast cancer cell line SK-BR-3/EPR with P-glycoprotein overexpression was established using stepwise long-term exposure to increasing concentration of epirubicin. The SK-BR-3/EPR cell line exhibited decreased cell proliferative activity, but enhanced cell invasive capacity. We showed that the expression of metastasis-related matrix metalloproteinase (MMP-2/9 was elevated in SK-BR-3/EPR cells. Moreover, SK-BR-3/EPR cells showed elevated activation of STAT3. Activation of STAT3 signaling is responsible for enhanced invasiveness of SK-BR-3/EPR cells through upregulation of MMP-2/9. STAT3 is a well-known oncogene and is frequently implicated in tumorigenesis and chemotherapeutic resistance. Our findings augment insight into the mechanism underlying the functional association between MDR and cancer invasiveness.

  4. Elevated STAT3 Signaling-Mediated Upregulation of MMP-2/9 Confers Enhanced Invasion Ability in Multidrug-Resistant Breast Cancer Cells.

    Science.gov (United States)

    Zhang, Fei; Wang, Zhiyong; Fan, Yanling; Xu, Qiao; Ji, Wei; Tian, Ran; Niu, Ruifang

    2015-10-16

    The development of multidrug resistance greatly impedes effective cancer therapy. Recent advances in cancer research have demonstrated that acquisition of multidrug resistance by cancer cells is usually accompanied by enhanced cell invasiveness. Several lines of evidence indicated that cross activation of other signaling pathways during development of drug resistance may increase invasive potential of multidrug-resistant (MDR) cancer cells. However, the accurate mechanism of this process is largely undefined. In this study, to better understand the associated molecular pathways responsible for cancer progression induced by drug resistance, a MDR human breast cancer cell line SK-BR-3/EPR with P-glycoprotein overexpression was established using stepwise long-term exposure to increasing concentration of epirubicin. The SK-BR-3/EPR cell line exhibited decreased cell proliferative activity, but enhanced cell invasive capacity. We showed that the expression of metastasis-related matrix metalloproteinase (MMP)-2/9 was elevated in SK-BR-3/EPR cells. Moreover, SK-BR-3/EPR cells showed elevated activation of STAT3. Activation of STAT3 signaling is responsible for enhanced invasiveness of SK-BR-3/EPR cells through upregulation of MMP-2/9. STAT3 is a well-known oncogene and is frequently implicated in tumorigenesis and chemotherapeutic resistance. Our findings augment insight into the mechanism underlying the functional association between MDR and cancer invasiveness.

  5. Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

    Science.gov (United States)

    Ammazzalorso, Alessandra; De Filippis, Barbara; Campestre, Cristina; Laghezza, Antonio; Marrone, Alessandro; Amoroso, Rosa; Tortorella, Paolo; Agamennone, Mariangela

    2016-01-01

    Matrix metalloproteinases (MMPs) are an important family of zinc-containing enzymes with a central role in many physiological and pathological processes. Although several MMP inhibitors have been synthesized over the years, none reached the market because of off-target effects, due to the presence of a zinc binding group in the inhibitor structure. To overcome this problem non-zinc-binding inhibitors (NZIs) have been recently designed. In a previous article, a virtual screening campaign identified some hydroxynaphtyridine and hydroxyquinoline as MMP-2 non-zinc-binding inhibitors. In the present work, simplified analogues of previously-identified hits have been synthesized and tested in enzyme inhibition assays. Docking and molecular dynamics studies were carried out to rationalize the activity data. PMID:27782083

  6. Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

    Directory of Open Access Journals (Sweden)

    Alessandra Ammazzalorso

    2016-10-01

    Full Text Available Matrix metalloproteinases (MMPs are an important family of zinc-containing enzymes with a central role in many physiological and pathological processes. Although several MMP inhibitors have been synthesized over the years, none reached the market because of off-target effects, due to the presence of a zinc binding group in the inhibitor structure. To overcome this problem non-zinc-binding inhibitors (NZIs have been recently designed. In a previous article, a virtual screening campaign identified some hydroxynaphtyridine and hydroxyquinoline as MMP-2 non-zinc-binding inhibitors. In the present work, simplified analogues of previously-identified hits have been synthesized and tested in enzyme inhibition assays. Docking and molecular dynamics studies were carried out to rationalize the activity data.

  7. MMP-2 inhibits PCSK9-induced degradation of the LDL receptor in Hepa1-c1c7 cells.

    Science.gov (United States)

    Wang, Xiang; Berry, Evan; Hernandez-Anzaldo, Samuel; Sun, Difei; Adijiang, Ayinuer; Li, Liang; Zhang, Dawei; Fernandez-Patron, Carlos

    2015-02-13

    Low-density lipoprotein receptor (LDLR) catalyzes the uptake of LDL-cholesterol by liver and peripheral organs. The function of the LDLR is antagonized by pro-protein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR at the plasma membrane inducing LDLR degradation. Here, we report that matrix metalloproteinase-2 (MMP-2) interacts with and cleaves PCSK9, as evidenced by proteomic, chemical cross-linkage, blue native-PAGE and domain-specific antibodies Western blot analyses. Furthermore, MMP-2 overexpression renders Hepa1-c1c7 cells resistant to PCSK9-induced LDLR degradation. The data suggest that pathological MMP-2 overexpression may protect the LDLR from PCSK-9-induced degradation.

  8. Tumour-targeting properties of antibodies specific to MMP-1A, MMP-2 and MMP-3

    Energy Technology Data Exchange (ETDEWEB)

    Pfaffen, Stefanie; Frey, Katharina; Stutz, Irene; Roesli, Christoph; Neri, Dario [Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zuerich, Zuerich (Switzerland)

    2010-08-15

    Matrix metalloproteinases (MMPs), a group of more than 20 zinc-containing endopeptidases, are upregulated in many diseases, but several attempts to use radiolabelled MMP inhibitors for imaging tumours have proved unsuccessful in mouse models, possibly due to the limited specificity of these agents or their unfavourable pharmacokinetic profiles. In principle, radiolabelled monoclonal antibodies could be considered for the selective targeting and imaging of individual MMPs. We cloned, produced and characterized high-affinity monoclonal antibodies specific to murine MMP-1A, MMP-2 and MMP-3 in SIP (small immunoprotein) miniantibody format using biochemical and immunochemical methods. We also performed comparative biodistribution analysis of their tumour-targeting properties at three time points (3 h, 24 h, 48 h) in mice bearing subcutaneous F9 tumours using radioiodinated protein preparations. The clinical stage L19 antibody, specific to the alternatively spliced EDB domain of fibronectin, was used as reference tumour-targeting agent for in vivo studies. All anti-MMP antibodies and SIP(L19) strongly stained sections of F9 tumours when assessed by immunofluorescence methods. In biodistribution experiments, SIP(SP3), specific to MMP-3, selectively accumulated at the tumour site 24 and 48 h after intravenous injection, but was rapidly cleared from other organs. By contrast, SIP(SP1) and SIP(SP2), specific to MMP-1A and MMP-2, showed no preferential accumulation at the tumour site. Antibodies specific to MMP-3 may serve as vehicles for the efficient and selective delivery of imaging agents or therapeutic molecules to sites of disease. (orig.)

  9. 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.

  10. Structural basis for matrix metalloproteinase-2 (MMP-2)-selective inhibitory action of β-amyloid precursor protein-derived inhibitor.

    Science.gov (United States)

    Hashimoto, Hiroshi; Takeuchi, Tomoka; Komatsu, Kyoko; Miyazaki, Kaoru; Sato, Mamoru; Higashi, Shouichi

    2011-09-23

    Unlike other synthetic or physiological inhibitors for matrix metalloproteinases (MMPs), the β-amyloid precursor protein-derived inhibitory peptide (APP-IP) having an ISYGNDALMP sequence has a high selectivity toward MMP-2. Our previous study identified amino acid residues of MMP-2 essential for its selective inhibition by APP-IP and demonstrated that the N to C direction of the decapeptide inhibitor relative to the substrate-binding cleft of MMP-2 is opposite that of substrate. However, detailed interactions between the two molecules remained to be clarified. Here, we determined the crystal structure of the catalytic domain of MMP-2 in complex with APP-IP. We found that APP-IP in the complex is indeed embedded into the substrate-binding cleft of the catalytic domain in the N to C direction opposite that of substrate. With the crystal structure, it was first clarified that the aromatic side chain of Tyr(3) of the inhibitor is accommodated into the S1' pocket of the protease, and the carboxylate group of Asp(6) of APP-IP coordinates bidentately to the catalytic zinc of the enzyme. The Ala(7) to Pro(10) and Tyr(3) to Ile(1) strands of the inhibitor extend into the nonprime and the prime sides of the cleft, respectively. Therefore, the decapeptide inhibitor has long range contact with the substrate-binding cleft of the protease. This mode of interaction is probably essential for the high MMP-2 selectivity of the inhibitor because MMPs share a common architecture in the vicinity of the catalytic center, but whole structures of their substrate-binding clefts have sufficient variety for the inhibitor to distinguish MMP-2 from other MMPs.

  11. 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.

  12. Caffeine induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in human leukemia U937 cells via Ca2+/ROS-mediated suppression of ERK/c-fos pathway and activation of p38 MAPK/c-jun pathway.

    Science.gov (United States)

    Liu, Wen-Hsin; Chang, Long-Sen

    2010-09-01

    Caffeine attenuated invasion of human leukemia U937 cells with characteristic of decreased protein expression and mRNA levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Down-regulation of MMP-2 and MMP-9 in U937 cells was abrogated by abolishment of caffeine-elicited increase in intracellular Ca(2+) concentration and ROS generation. Pretreatment with BAPTA-AM (Ca(2+) chelator) and N-acetylcysteine (ROS scavenger) abolished caffeine-induced ERK inactivation and p38 MPAK activation. Moreover, caffeine treatment led to MAPK phosphatase-1 (MKP-1) down-regulation and protein phosphatase 2A catalytic subunit (PP2Ac) up-regulation, which were involved in cross-talk between p38 MAPK and ERK. Transfection of constitutively active MEK1 or pretreatment with SB202190 (p38 MAPK inhibitor) restored MMP-2 and MMP-9 protein expression in caffeine-treated cells. Caffeine treatment repressed ERK-mediated c-Fos phosphorylation but evoked p38 MAPK-mediated c-Jun phosphorylation. Knock-down of c-Fos and c-Jun by siRNA reflected that c-Fos counteracted the effect of c-Jun on MMP-2/MMP-9 down-regulation. Taken together, our data indicate that MMP-2/MMP-9 down-regulation in caffeine-treated U937 cells is elicited by Ca(2+)/ROS-mediated suppression of ERK/c-Fos pathway and activation of p38 MAPK/c-Jun pathway.

  13. The expressions and significance of MMP-2 and TIMP-2 in human pancreatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Matrix metalloproteinases(MMPs)are a fami-ly of zinc-dependent proteinases that are associatedwith the tumorigenic process.Essential steps in thisprocess are the degradation of basement membranesand remodeling of the extracellular matrix(ECM)by proteolytic enzymes such as MMPs,which areregulated by their tissue inhibitors of metalloprotei-nases(TI MPs).MMPs and TI MPs are associatedwiththe invasion and metastasis of tumor,these en-zymes can degrade the various components of theECM[1-4].This study is to prov...

  14. Relaxin stimulates MMP-2 and α-smooth muscle actin expression by human periodontal ligament cells

    NARCIS (Netherlands)

    Henneman, S.; Bildt, M.M.; Groot, J. de; Kuijpers-Jagtman, A.M.; Von den Hoff, J.W.

    2008-01-01

    The main cells in the periodontal ligament (PDL) are the fibroblasts, which play an important role in periodontal remodelling. Matrix metalloproteinases (MMPs) are largely responsible for the degradation of extracellular matrix proteins in the PDL. Previous studies have indicated that MMP production

  15. Relaxin stimulates MMP-2 and alpha-smooth muscle actin expression by human periodontal ligament cells.

    NARCIS (Netherlands)

    Henneman, S.; Bildt, M.M.; Degroot, J.; Kuijpers-Jagtman, A.M.; Hoff, J.W. Von den

    2008-01-01

    The main cells in the periodontal ligament (PDL) are the fibroblasts, which play an important role in periodontal remodelling. Matrix metalloproteinases (MMPs) are largely responsible for the degradation of extracellular matrix proteins in the PDL. Previous studies have indicated that MMP production

  16. Data in support of the negative influence of divalent cations on (-)-epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2).

    Science.gov (United States)

    Deb, Gauri; Batra, Sahil; Limaye, Anil M

    2016-03-01

    In this data article we have provided evidence for the negative influence of divalent cations on (-)-epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2) activity in cell-free experiments. Chelating agents, such as EDTA and sodium citrate alone, did not affect MMP-2 activity. While EDTA enhanced, excess of divalent cations interfered with EGCG-mediated inhibition of MMP-2.

  17. Arctigenin, a lignan from Arctium lappa L., inhibits metastasis of human breast cancer cells through the downregulation of MMP-2/-9 and heparanase in MDA-MB-231 cells.

    Science.gov (United States)

    Lou, Chenghua; Zhu, Zhihui; Zhao, Yaping; Zhu, Rui; Zhao, Huajun

    2017-01-01

    Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L. which has been widely used as a diuretic and a diaphoretic in Traditional Chinese Medicine. In the present study, the authors investigated the effects of arctigenin on tumor migration and invasion in aggressive human breast cancer cells. The MTT assay results showed that arctigenin did not show a significant cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound healing migration and Boyden chamber invasion assays demonstrated that arctigenin significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells. Furthermore, gelatin zymography results showed that arctigenin reduced the activity of MMP-2 and MMP-9. Western blot analysis results demonstrated that the expression of MMP-2, MMP-9 and heparanase proteins was significantly downregulated following the treatment of arctigenin. Finally, the antiangiogenic activity of arctigenin was also examined by the chick embryo chorioallantoic membrane (CAM) assay. Arctigenin treatment significantly inhibited angiogenesis in the CAM. In conclusion, the results revealed that arctigenin significantly inhibited the migration and invasion of MDA-MB-231 cells by downregulating MMP-2, MMP-9 and heparanase expression. However, further studies are still necessary to investigate the exact mechanisms involved and to explore signal transduction pathways to better understand the biological mechanisms.

  18. Study on Serum Concentrations of MMP-2 TIMP-2 TIMP-1 Copper Zinc and Terminal Propeptides of Precollagen in Inguinal Patients with Hernia%腹股沟疝病人血清 MMP-2 TIMP-2 TIMP-1锌铜及前胶原末端肽的测定分析

    Institute of Scientific and Technical Information of China (English)

    李剑; 孙启玉; 张学军; 孙启天; 邢恩鸿; 高英梅; 于海平

    2014-01-01

    Objective:To investigate the expression of MMP-2, TIMP-2, TIMP-1, copper, zinc and terminal propeptides of precollagen in the serum of inguinal hernia and explore the pathogenesis of the dis-ease.Method:The samples were collected from inguinal hernia patients ( direct n=35, indirect n=35, re-current n=17) and from healthy controls ( n=35) .The indicators in serum were measured according to the instruction books of the reagent kits .Result:Serum levels of MMP-2 in direct and recurrent hernia patients were higher than indirect hernia patients and controls (P<0.05).TIMP-2 and TIMP-1 were lower(P<0. 05).Serum levels of Cu and Zn in four groups (especially the recurrent hernia group) have no significant difference.The results of serum PICP/PⅢNP were lower in direct and recurrent groups compared to indirect group and controls(P<0.05).Conclusion:The changes of serum MMP-2, TIMP-2, TIMP-1 and PICP/PⅢNP might be associated with the development of direct and recurrent inguinal hernia .%目的:比较血清MMP-2、TIMP-2、TIMP-1、锌、铜及前胶原末端肽的表达,探讨腹股沟疝的发病机制。方法:以在我院行疝修补术患者为研究对象,其中直疝35例;斜疝35例;复发疝17例;正常对照35例。收集各组病人血清标本,对血清指标进行检测。结果:直疝及复发疝组病人血清MMP-2水平显著高于正常组及斜疝组(P<0.05),尤其为复发疝;血清TIMP-2及TIMP-1水平在直疝和复发疝明显低于正常组及斜疝组( P<0.05);血清铜和锌含量在各组无显著性差异;直疝及复发疝组血清前胶原末端肽PⅠCP/PⅢNP比值显著低于正常组及斜疝组,( P<0.05)。结论:和结缔组织代谢相关指标MMP-2、TIMP-2、TIMP-1及PICP/PⅢNP 的改变参与了直疝的发生,并和疝术后复发密切相关。

  19. 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.

  20. Peptide from the C-terminal domain of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) inhibits membrane activation of matrix metalloproteinase-2 (MMP-2).

    Science.gov (United States)

    Xu, Xiaoping; Mikhailova, Margarita; Chen, Zhihua; Pal, Sanjay; Robichaud, Trista K; Lafer, Eileen M; Baber, Sam; Steffensen, Bjorn

    2011-09-01

    Cellular activation of latent matrix metalloproteinase-2 (proMMP-2) requires formation of a cell membrane-associated activation complex that involves specific binding between the hemopexin domain of proMMP-2 (PEX) and the C-terminal domain of tissue inhibitor of matrix metalloproteinases-2 (C-TIMP-2). In this study, we tested the feasibility of inhibiting activation of proMMP-2 by exogenous inhibitors, which block the binding between PEX and TIMP-2. The recombinant C-TIMP-2 and synthetic peptides from C-TIMP-2 were used as inhibitors for proMMP-2 activation. Recombinant C-TIMP-2 bound specifically to both the catalytically inactive MMP-2(E404A) and the C-terminal domain of MMP-2 (PEX) in a concentration dependent manner with apparent K(d) of 3.9×10(-7)M and 1.7×10(-7)M, respectively. Moreover, C-TIMP-2 competed the binding between MMP-2(E404A) and full-length TIMP-2. Finally, activity assays showed that addition of C-TIMP-2 to HT-1080 fibrosarcoma cells inhibited proMMP-2 activation in a concentration-dependent manner. We then designed a synthetic peptide, P175L, consisting of 20 residues from the PEX-binding tail region of C-TIMP-2. P175L bound PEX and inhibited cell membrane-mediated activation of proMMP-2 in a concentration dependent manner. Deletion of the last 9 tail residues of C-TIMP-2 in P175L abrogated the inhibitory activities of the peptide showing that these residues were essential for function. Overall, these experiments have demonstrated that proMMP-2 activation can be inhibited by exogenous inhibitors which points to a potential strategy for MMP-2 specific inhibition.

  1. Concentrations of MMP-2 in gingival crevicular fluid of porcelain teeth with three different alloys%三种金属烤瓷冠修复后龈沟液中MMP-2水平检测

    Institute of Scientific and Technical Information of China (English)

    许卫星; 苏俭生; 袁剑鸣

    2012-01-01

    目的 研究镍铬合金、钴铬合金、金合金三组金属烤瓷冠修复前后,龈沟液(gingival crevicular fluid,GCF)中基质金属蛋白酶-2(matrix metalloproteinase,MMP-2)水平变化,提示三种合金烤瓷冠在不同时期对牙周组织的刺激程度.方法 临床随机选择三种金属烤瓷冠修复患者共45例,每组各15例,测定在修复前、修复后1个月、3个月、6个月GCF量并采用双抗体夹心酶联免疫吸附法(ABC-ELISA)检测同期GCF中MMP-2水平.结果 镍铬合金烤瓷冠GCF量、MMP-2水平在不同检测周期差异有显著性(P<0.01),钴铬合金、金合金烤瓷冠修复后MMP-2水平在不同检测周期差异无显著性(P>0.05).结论 MMP-2可作为对不同金属烤瓷冠内冠材料刺激牙周组织的评价指标,临床应采用生物相容性好的合金作为内冠材料.%Objective To measure MMP-2 concentrations in gingival crevicular fluid ( GCF) of porcelain teeth coated with Ni-Cr, Co-Cr or gold alloy at different time period, and to demonstrate the degree of stimulation by these alloy on gingivae. Methods Sandwich enzyme-linked immunosorbent assay(ELISA) was used to determine the concentration and total amount of MMP-2 in gingival crevicular fluids in 45 randomly selected cases of porcelain teeth coated with Ni-Cr, Co-Cr or gold alloy, with 15 cases in each group. The assay was performed before and at 1, 3, 6 months after treatment. Results There was significant difference in the total amounts of MMP-2 and GCF volume for the Ni-Cr alloy coated porcelain teeth in different time period(P 0. 05 ). Conclusion MMP-2 is a useful assessment criterion for the evaluation of degree of stimulation on gingivae by different alloy coating materials in porcelain teeth. The bio-compatibility of alloy coating for porcelain teeth should be carefully considered for the clinical application.

  2. A monoclonal antibody interferes with TIMP-2 binding and incapacitates the MMP-2-activating function of multifunctional, pro-tumorigenic MMP-14/MT1-MMP

    DEFF Research Database (Denmark)

    Shiryaev, S A; Remacle, A G; Golubkov, V S;

    2013-01-01

    Matrix metalloproteinases (MMPs) and, especially membrane type 1 (MT1)-MMP/MMP-14, are promising drug targets in malignancies. In contrast with multiple small-molecule and protein pan-inhibitors of MT1-MMP cleavage activity, the murine 9E8 monoclonal antibody targets the MMP-2-activating function...... tissue inhibitor of metalloproteinases-2 (TIMP-2) association with MT1-MMP. As a result, the 9E8 antibody incapacitates the TIMP-2-dependent MMP-2-activating function alone rather than the general enzymatic activity of human MT1-MMP. The specific function of the 9E8 antibody we determined directly...... supports an essential, albeit paradoxical, role of the protein inhibitor (TIMP-2) in MMP-2 activation via a unique membrane-tethered mechanism. In this mechanism, the formation of a tri-molecular MT1-MMPTIMP-2MMP-2 complex is required for both the capture of the soluble MMP-2 proenzyme by cells...

  3. Matrix metalloproteinase-2 functional promoter polymorphism G1575A is associated with elevated circulatory MMP-2 levels and increased risk of cardiovascular disease in systemic lupus erythematosus patients.

    Science.gov (United States)

    Bahrehmand, F; Vaisi-Raygani, A; Kiani, A; Rahimi, Z; Tavilani, H; Navabi, S J; Shakiba, E; Hassanzadeh, N; Pourmotabbed, T

    2012-05-01

    Matrix metalloproteinase-2 (MMP-2) is a zinc dependent endonuclease that degrades type IV collagen, the major structural component of basement membranes. MMP-2 functional promoter polymorphism G1575A affects circulating level of MMP-2 and may be considered an important genetic determinant of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) patients. In this study, association between MMP-2 1575A allele with serum MMP-2, neopterin and lipid-lipoprotein levels and with SLE and developing CVD was investigated. The present case-control study consisted of 109 SLE patients with and without CVD (mean age, 35.6 years) and 101 gender- and age-matched, unrelated, healthy controls (mean age, 37.1 years) from the population in the west of Iran. MMP-2 1575G/A polymorphism was detected by polymerase chain reaction (restriction fragment length polymorphism) PCR-RFLP, serum MMP-2, neopterin and lipid levels were determined by enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC) and enzyme assay, respectively. The presence of MMP-2 G1575A allele was found to be associated with SLE and developed CVD (OR = 1.78, p = 0.029 and OR = 3.43, p = 0.025, respectively). The SLE patients with MMP-2 A (G/A + A/A) allele had higher MMP-2 activity (301 ± 166 vs. 194 ± 35.5, p = 0.002), neopterin (29.4 ± 39.4 vs. 7.3 ± 4.6, p = 0.005), LDL-C (120 ± 25.7 vs. 87 ± 39.3, p = 0.045) and lower HDL-C (39.6 ± 11 vs. 45.9 ± 11.8, p = 0.031) levels than the control subjects. There was a significantly positive correlation between MMP-2 level with neopterin, total cholesterol and TG levels and negative correlation with HDL-C level in SLE patients with CVD. MMP-2 G1575A allele may be a risk factor for SLE. The carriers of this allele have high levels of MMP-2, neopterin, total cholesterol and TG and lower levels of HDL, thus, they are more likely to develop heart disease.

  4. Synthesis, Biological Evaluation, and Docking of Dihydropyrazole Sulfonamide Containing 2-hydroxyphenyl Moiety: A Series of Novel MMP-2 Inhibitors.

    Science.gov (United States)

    Wang, Peng-Fei; Qiu, Han-Yue; Baloch, Shahla Karim; Gong, Hai-Bin; Wang, Zhong-Chang; Zhu, Hai-Liang

    2015-12-01

    In this study, we synthesized a series of dihydropyrazole sulfonamide derivatives containing 2-hydroxyphenyl moiety as antitumor agents to target the matrix metalloproteinase-2 (MMP-2). All of the synthesized compounds were examined by bioactivity assays, in which compound 4c turned out as a potential antagonist of MMP-2 along with potent anticancer activity against four tumor cell lines. Structure-activity relationship analysis was also performed to examine how structural changes impacted the bioactivity. Suggested to be caused by the induction of apoptosis, the antitumor mechanism of 4c was further confirmed by PI combining with annexin V-FITC staining assay using flow cytometry analysis. These new findings along with molecular docking observations suggested that compound 4c could be developed as a potential anticancer agent.

  5. 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.

  6. 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.

  7. TGF-{beta}1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-{kappa}B/IL-6/MMP-2

    Energy Technology Data Exchange (ETDEWEB)

    Binker, Marcelo G. [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); CBRHC Research Center, Buenos Aires (Argentina); Binker-Cosen, Andres A. [CBRHC Research Center, Buenos Aires (Argentina); Gaisano, Herbert Y. [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); Cosen, Rodica H. de [CBRHC Research Center, Buenos Aires (Argentina); Cosen-Binker, Laura I., E-mail: laura.cosen.binker@utoronto.ca [Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 (Canada); CBRHC Research Center, Buenos Aires (Argentina)

    2011-02-04

    Research highlights: {yields} Rac1 mediates TGF-{beta}1-induced SW1990 invasion through MMP-2 secretion and activation. {yields} NADPH-generated ROS act downstream of Rac1 in TGF-{beta}1-challenged SW1990 cells. {yields} TGF-{beta}1-stimulated ROS activate NF-{kappa}B in SW1990 cells. {yields} NF{kappa}B-induced IL-6 release is required for secretion and activation of MMP-2 in SW1990 cells. -- Abstract: Human pancreatic cancer invasion and metastasis have been found to correlate with increased levels of active matrix metalloproteinase 2 (MMP-2). The multifunctional cytokine transforming growth factor beta 1 (TGF-{beta}1) has been shown to increase both secretion of MMP-2 and invasion by several pancreatic cancer cell types. In the present study, we investigated the signaling pathway involved in TGF-{beta}1-promoted MMP-2 secretion and invasion by human pancreatic cancer cells SW1990. Using specific inhibitors, we found that stimulation of these tumor cells with TGF-{beta}1 induced secretion and activation of the collagenase MMP-2, which was required for TGF-{beta}1-stimulated invasion. Our results also indicate that signaling events involved in TGF-{beta}1-enhanced SW1990 invasiveness comprehend activation of Rac1 followed by generation of reactive oxygen species through nicotinamide adenine dinucleotide phosphate-oxidase, activation of nuclear factor-kappa beta, release of interleukin-6, and secretion and activation of MMP-2.

  8. ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

    Institute of Scientific and Technical Information of China (English)

    Xu Li; Ying Meng; Xi-Shan Yang; Ling-Fei Mi; Shao-Xi Cai

    2005-01-01

    AIM: Angiotensin Ⅱ has pro-fibrotic function in the liver.Blockade of the renin-angiotensin-aldosterone-system (RAAS) attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensinconverting enzyme inhibitor (ACEI) on the progression of rat hepatic fibrosis.METHODS: Forty male Wistar rats were divided into three groups. Model group (Mo): The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group (Pe): The rats were injected subcutaneously with administrated. Control group (Nc): the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed.The liver sections were stained with Masson. The protein expressions of AT1R, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB (NF-κB) DNA binding activity was examined by EMSA (Electrophoretic gel mobility shift assay). Matrix metalloproteinase-2,9(MMP-2,9) activity was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radioimmunoassays.RESULTS: Using Western blot, we clearly provided direct evidence for the expression of AT1R in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score,protein levels of AT1R, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA binding activity markedly increased in model group, perindopril treatment considerably reduced NF-κB DNA binding activity.CONCLUSION: Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB,NF-κB and MMP-2,9.

  9. Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors

    Institute of Scientific and Technical Information of China (English)

    Takahiro Nemoto; Shunichiro Kubota; Hideyuki Ishida; Nobuo Murata; Daijo Hashimoto

    2005-01-01

    AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively.RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels.CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.

  10. 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.

  11. MMP-1和MMP-2在肝纤维化组织中的表达和意义

    Institute of Scientific and Technical Information of China (English)

    安运卿; 马天江

    2003-01-01

    目的:探讨MMP-1和MMP-2在肝纤维化组织中的作用及其机制.方法:应用免疫组化法并用图像分析技术定量检测28例手术切除的肝纤维化组织标本中MMP-1和MMP-2的表达.结果:正常肝组织与肝纤维化组织MMP-1表达无显著性差异(P>0.05),而MMP-2的表达在肝纤维化组织中明显高于正常肝组织(P<0.01).结论:MMP-1和MMP-2可能在肝纤维化的发生和发展中有重要作用.

  12. 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.

  13. Functional cooperativity by direct interaction between PAK4 and MMP-2 in the regulation of anoikis resistance, migration and invasion in glioma.

    Science.gov (United States)

    Kesanakurti, D; Chetty, C; Rajasekhar Maddirela, D; Gujrati, M; Rao, J S

    2012-12-20

    Gliomas display anoikis resistance, enhanced invasion in to the adjacent brain parenchyma and eventually recur despite using the standard therapies. Our studies on increased anoikis sensitization in matrix metalloproteinase-2 (MMP-2)-knockdown 4910 and 5310 human glioma xenograft cells were interestingly correlated with p21-activated kinase 4 (PAK4) inhibition, prompting us to further investigate the role of PAK4 in glioma. Here, we report the PAK4 upregulation in positive correlation with increasing glioma pathological grades. The siRNA-mediated PAK4 knockdown elevated anoikis, and inhibited invasion and migration by downregulating MMP-2, αvβ3-integrin and phospho-epidermal growth factor receptor (phospho-EGFR). The cDNA-PCR arrays revealed a transcriptional suppression of essential proteins involved in cell proliferation and adhesion in PAK4-knockdown cells. Most importantly, glutathione S-transferase pull-down assays demonstrated the MMP-2 as a new PAK4-interacting protein which binds to PAK4 kinase domain. Individual EGFR/ErbB2 inhibitor and αvβ3 antibody treatments in PAK4si-treated cells indicated the regulation of αvβ3/EGFR survival signaling by PAK4. Overexpression of PAK4 significantly reversed the MMP2si-induced cell death in both cell lines. Codepletion of PAK4 and MMP-2 resulted in robust anoikis-mediated cell death, and severely inhibited invasive and migratory properties in these cells. PAK4si inhibited in vivo tumor growth in nude mice by inhibiting MMP-2, β3-integrin and phospho-EGFR levels in tumors. Our findings indicate a physical association between PAK4 and MMP-2, and suggest the future therapeutic potential of PAK4/MMP-2 dual targeting in glioma treatment.

  14. 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.

  15. 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.

  16. Exhaustive exercise with different rest periods changes the collagen content and MMP-2 activation on the calcaneal tendon.

    Science.gov (United States)

    De Aro, Andrea Aparecida; Ferrucci, Danilo Lopes; Borges, Frederico Padovan; Stach-Machado, Dagmar Ruth; Macedo, Denise Vaz; Pimentel, Edson Rosa

    2014-02-01

    Tendons adapt to different mechanical stimuli through a remodeling process involving metalloproteinases (MMPs) and collagen synthesis. The purpose of this study was to investigate the activities of MMP-2 and MMP-9 and the collagen content in tendons after exhaustive acute exercise sessions over the course of 1, 3, or 6 days, with 1-hr or 3-hr rest periods between each session. Wistar rats were grouped into control (C), trained with 1-hr (groups 1d1h, 3d1h, and 6d1h) and trained with 3-hr (groups 1d3h, 3d3h and 6d3h) groups with rest periods between the treadmill running sessions, for 1, 3, and 6 days. The analysis of MMP-2 showed a larger presence of the latent isoform in the 1d3h group and a larger presence of the active isoform in the 6d3h group compared to the control. No differences were detected for MMP-9. A lower concentration of hydroxyproline was found in the 6d3h group compared to the 6d1h group. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed more prominent collagen bands in the 6d3h group, which was confirmed by Western blotting for collagen type I. A higher concentration of glycosaminoglycans was observed in the 3d3h group compared to the 3d1h group, and the 6d3h group presented the highest value for non-collagenous proteins compared to other groups. In conclusion, different rest periods between exercise sessions had different effects on the composition of the calcaneal tendon because a greater activation of MMP-2 and a reduction of total collagen were observed on day 6 of exercise with 3-hr rest periods compared to 1-hr rest periods.

  17. Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities

    Energy Technology Data Exchange (ETDEWEB)

    Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de; Alexi, Pascal; Tihaa, Lidia; Haas, Ute; Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de

    2015-02-13

    Platelet-derived growth factor-D (PDGF-D) is a more recent recognized growth factor involved in the regulation of several cellular processes, including cell proliferation, transformation, invasion, and angiogenesis by binding to and activating its cognate receptor PDGFR-β. After bile duct ligation or in the carbon tetrachloride-induced hepatic fibrosis model{sub ,} PDGF-D showed upregulation comparable to PDGF-B. Moreover, adenoviral PDGF-D gene transfer induced hepatic stellate cell proliferation and liver fibrosis. We here investigated the molecular mechanism of PDGF-D involvement in liver fibrogenesis. Therefore, the GRX mouse cell line was stimulated with PDGF-D and evaluated for fibrotic markers and PDGF-D signaling pathways in comparison to the other PDGF isoforms. We found that PDGF-D failed to enhance Col I and α-smooth muscle actin (α-SMA) production but has capacity to upregulate expression of the tissue inhibitor of metalloprotease 1 (TIMP-1) resulting in attenuation of MMP-2 and MMP-9 gelatinase activity as indicated by gelatinase zymography. This phenomenon was restored through application of a PDGF-D neutralizing antibody. Unexpectedly, PDGF-D incubation decreased both PDGFR-α and -β in mRNA and protein levels, and PDGF-D phosphorylated typrosines specific for PDGFR-α and -β. We conclude that PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity of the TIMP-1/MMP system and that PDGF-D signaling is mediated through both PDGF-α and -β receptors. - Highlights: • PDGF-D signals through PDGF receptor type α and β. • PDGF-D modulates extracellular matrix homeostasis and remodeling. • Like PDGF-B, PDGF-D triggers phosphorylation of PLC-γ, Akt/PKB, JNK, ERK1/2, and p38. • PDGF-D induces TIMP-1 expression through ERK and p38 MAPK. • PDGF-D attenuates MMP-2 and MMP-9 gelatinase activities.

  18. GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity

    Energy Technology Data Exchange (ETDEWEB)

    Fiorentini, Chiara; Bodei, Serena; Bedussi, Francesca; Fragni, Martina; Bonini, Sara Anna [Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia (Italy); Simeone, Claudio; Zani, Danilo [Division of Urology, Department of Surgery, Radiology and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia (Italy); Berruti, Alfredo [Medical Oncology, Department of Surgery, Radiology, and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia (Italy); Missale, Cristina; Memo, Maurizio; Spano, PierFranco [Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia (Italy); Sigala, Sandra, E-mail: sigala@med.unibs.it [Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia (Italy)

    2014-04-15

    Non-metastatic glycoprotein melanoma protein B (GPNMB), also known as osteoactivin (OA) is expressed in a wide array of tumors and represents an emerging target for drug development. In this study, we investigated the role of GPNMB/OA in the progression of human metastatic DU145 and PC3 prostate cancer cells. GPNMB/OA contribution in PCa malignant phenotype has been analyzed by small interfering RNA-induced GPNMB/OA silencing. We found that following GPNMB/OA silencing the migration capability of both DU145 and PC3 cells, evaluated by using in vitro invasivity assay, as well as the metalloproteinases MMP-2 and MMP-9 activity were equally strongly inhibited. By contrast knocking down GPNMB/OA weakly attenuated cell proliferation rate of DU145, an effect that paralleled with an increase number of apoptotic cells. However, PC3 cell growth seems to be not affected by GPNMB/OA. Together, these data reveal that GPNMB/OA acts as a critical molecular mediator promoting the acquisition of the more aggressive, pro-metastatic phenotype distinctive of human DU145 and PC3 cell lines. - Highlights: • GPNMB/OA expression correlates with DU145 and PC3 cells malignant phenotype. • GPNMB/OA silencing affects the migration capability of both DU145 and PC3 cells. • GPNMB/OA increases invasiveness by up-regulating MMPs activity. • GPNMB/OA promotes DU145 and PC3 cells progression into a more aggressive phenotype.

  19. 肾细胞癌MMP-2、MMP-3和TIMP-2表达与浸润转移

    Institute of Scientific and Technical Information of China (English)

    钱智玲; 张劲光; 韩辉; 张丽芝; 李泉林; 关宏伟

    2004-01-01

    目的 探讨肾细胞癌基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶抑制剂-2(TIMP-2)表达与浸润转移。方法 通过免疫组化S-P法检测66例肾细胞癌组织MMP-2、MMP-3和TIMP-2的半定量表达情况及其与肿瘤临床病理指标的关系。结果 肾细胞癌组织MMP-2、MMP-3、TIMP-2阳性表达主要表现在肿瘤细胞胞浆,胞膜亦有表达,阳性细胞呈散在、片状或灶状分布。少量间质细胞也有表达。肾癌组织MMP-2、MMP-3和TIMP-2阳性表达率分别为89.4%(59/66)、86.3%(57/66)、95.5%(63/66)。MMP-2和MMP-3表达与肾癌细胞类型(1.76±0.15和2.52±0.16,l_65±0.15和2.17±0.21 P<0.05)相关;MMP-2、MMP-3、TIMP-2及MMP-2/TIMP-2比率表达与肾癌包膜状况(1.80±0.17和2.29±0.17,1.60±0.16和2.10±0.19,2.49±0.13和1.97±0.18,0.70±0.08和1.37±0.18P均<0.05)相关;结论 肾癌细胞是MMP-2、MMP-3及TIMP-2高表达肿瘤,阳性表达具有异质性。MMP-2和MMP-3表达与肾癌细胞类型相关,颗粒细胞和混合细胞型表达明显高于透明细胞型,说明不同类型浸润能力不同。MMP-2、MMP-3、TIMP-2和MMP-2/TIMP-2比值在肾癌组织表达与包膜状况密切相关,且MMP-2、MMP-3和MMP-2/TIMP-2比值与肿瘤浸润呈正相关,TIMP-2与肿瘤浸润呈负相关,MMP-2/TIMP-2比值失衡导致浸润转移。

  20. Exogenous coenzyme Q10 modulates MMP-2 activity in MCF-7 cell line as a breast cancer cellular model

    Directory of Open Access Journals (Sweden)

    Mirmiranpour Hossein

    2010-11-01

    Full Text Available Abstract Background/Aims Matrix Metalloproteinases 2 is a key molecule in cellular invasion and metastasis. Mitochondrial ROS has been established as a mediator of MMP activity. Coenzyme Q10 contributes to intracellular ROS regulation. Coenzyme Q10 beneficial effects on cancer are still in controversy but there are indications of Coenzyme Q10 complementing effect on tamoxifen receiving breast cancer patients. Methods In this study we aimed to investigate the correlation of the effects of co-incubation of coenzyme Q10 and N-acetyl-L-cysteine (NAC on intracellular H2O2 content and Matrix Metalloproteinase 2 (MMP-2 activity in MCF-7 cell line. Results and Discussion Our experiment was designed to assess the effect in a time and dose related manner. Gelatin zymography and Flowcytometric measurement of H2O2 by 2'7',-dichlorofluorescin-diacetate probe were employed. The results showed that both coenzyme Q10 and N-acetyl-L-cysteine reduce MMP-2 activity along with the pro-oxidant capacity of the MCF-7 cell in a dose proportionate manner. Conclusions Collectively, the present study highlights the significance of Coenzyme Q10 effect on the cell invasion/metastasis effecter molecules.

  1. Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and matrix metalloproteinase-2 in neoplasms and precursor lesions derived from cutaneous squamous cells: An immunohistochemical study.

    Science.gov (United States)

    Ayva, Sebnem Kupana; Karabulut, Ayse Anil; Akatli, Ayşe Nur; Atasoy, Pinar; Bozdogan, Onder

    2013-10-01

    Extracellular matrix metalloproteinase inducer (CD147) is a transmembrane glycoprotein involved in the regulation of matrix metalloproteinases (MMPs). The study investigated CD147 and MMP-2 expression in epidermis of cutaneous squamous lesions. CD147 and MMP-2 expressions were evaluated immunohistochemically in 44 specimens: 18 actinic keratoses (AK), 6 squamous cell carcinomas in situ (SCCIS), 13 squamous cell carcinomas (SCC; peritumoral and invasive portions assessed), and 7 normal skins. Patterns of expression were assessed, with MMP-2 in nuclei (MMP-2n) and cytoplasm (MMP-2c) evaluated separately. The expression of each marker was quantified using a calculated immunohistochemical/histologic score (H-score). Correlations were analyzed for the marker H-scores in each study group. Associations between H-scores and histopathologic parameters were also evaluated. CD147 H-score was the highest in SCC (invasive islands), followed by AK, SCCIS, and control specimens, respectively. MMP-2n and MMP-2c H-scores were the highest in AK, followed by SCCIS, SCC, and control specimens, respectively. MMP-2c and MMP-2n H-scores were significantly higher in peritumoral epidermis than in invasive islands of SCC. MMP-2c and CD147 H-scores were positively correlated in the peritumoral SCCs. CD147 H-score was positively correlated with tumor differentiation in SCC. The findings suggest that overexpression of CD147 plays a role in the development of SCC.

  2. Predicting Novel Antitumor Agents: 3D-Pharmacophore Mapping of β-N-biaryl Ether Sulfonamide-Based Hydroxamates as Potentially MMP-2 Inhibitors.

    Science.gov (United States)

    Medeiros Turra, Kely; Pineda Rivelli, Diogo; Berlanga de Moraes Barros, Silvia; Fernanda Mesquita Pasqualoto, Kerly

    2014-09-01

    Matrix metalloproteinases (MMP) are a group of enzymes related to extracelular matrix remodeling. Some types of MMP are overexpressed by malignant tumors, mainly the MMP-2 subtype, and have been associated to cancer invasiveness and metastasis. A receptor-independent (RI) 4D-QSAR formalism was applied, herein, to a set of forty β-N-biaryl ether sulfonamide hydroxamates, previously reported as potent MMP-2 inhibitors, in order to map 3D-pharmacophore models and predict novel antitumor agents. The best RI 4D-QSAR model was statistically significant (N=30, r(2) =0.93, q(2) =0.88, five occupancy descriptors (GCOD), LSE=0.04, LOF=0.11, outliers=0), robust and not obtained by chance. The external predictability was 75 % (test set; N=8). A different orientation (binding mode) in the MMP-2 catalytic site was suggested regarding the most hydrophobic portion (R1 ) of the compounds' structure. Compounds were predicted and their inhibitory activity against MMP-2 was calculated by using the optimum RI 4D-QSAR model. The findings have provided interesting information to drive the designing and synthesis of novel potentially MMP-2 inhibitors against melanoma invasion.

  3. 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.

  4. BubR1 Acts as a Promoter in Cellular Motility of Human Oral Squamous Cancer Cells through Regulating MMP-2 and MMP-9

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    Chou-Kit Chou

    2015-07-01

    Full Text Available BubR1 is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubR1 was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC. However, the effect of BubR1 on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubR1 in the progression of OSCC and confirm the expression of BubR1 in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubR1 was markedly increased in four OSCC cell lines, Ca9-22, HSC3, SCC9 and Cal-27 cells, compared to two normal cells, normal human oral keratinocytes (HOK and human gingival fibroblasts (HGF. Moreover, the expression of BubR1 in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubR1 was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubR1 knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. Consistently, the activities of metastasis-associated metalloproteinases MMP-2 and MMP-9 were attenuated in BubR1 knockdown Ca9-22 cells, suggesting the role of BubR1 in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubR1 could be a prognostic index in OSCC patients.

  5. 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.

  6. 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.

  7. Worse prognosis in breast cancer patients can be predicted by immunohistochemical analysis of positive MMP-2 and negative estrogen and progesterone receptors

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    Edneia A. S. Ramos

    Full Text Available Summary Introduction: Breast cancer is the most cause of death, and approximately 90% of these deaths are due to metastases. Matrix metalloproteinase-2 (MMP-2 gelatinase activity is able to degrade a major constituent of the tumor microenvironment, type IV collagen. Two well-established proteins used as markers in clinical practice for breast cancer are the receptors for estrogen (ER and progesterone (PR. Although the presence of these receptors has been associated with a better prognosis, loss of these proteins can occur during tumor progression, with subsequent resistance to hormone therapy. Objective: To study the correlation among MMP-2, ER, and PR, as well as the establishment of the metastatic process in primary breast tumors. Method: Breast cancer samples (n=44 were analyzed by immunohistochemistry for MMP-2, ER, and PR. Results: We observed that 90% of patients who had metastases and died showed positive staining for MMP-2 (p=0.0082 for both. Using Kaplan-Meier analysis, we found that negative ER patients who were also positive for MMP-2 had even worse disease-free survival (DFS and overall survival (OS (p= 0.012 and p=0.005, respectively. Similar results were found in PR-negative patients for DFS (a trend p=0.077 and OS (p=0.038. Conclusion: Regardless of our small sample size (n=44, the data obtained strongly suggest that MMP-2 in combination with already well-established markers could help to predict the emergence of metastases and death in patients with breast cancer.

  8. Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors.

    Science.gov (United States)

    Kushlinskii, N E; Timofeev, Yu S; Solov'ev, Yu N; Gerstein, E S; Lyubimova, N V; Bulycheva, I V

    2014-08-01

    Serum levels of sRANKL, RANK, OPG, IL-8, IL-6, IL-16, MMP-2, and calcitonin were measured by ELISA in patients with malignant, borderline, and benign bone tumors and in healthy individuals (control). Serum levels of RANK, OPG, IL-8, IL-6, and the OPG/sRANKL ratio were significantly higher, while the level of MMP-2 was significantly lower in patients with bone tumors than in controls. Serum concentration of IL-16 in osteosarcoma patients was significantly lower than in chondrosarcoma patients. No significant differences between bone sarcomas of different differentiation were detected for any of the studied markers. Calcitonin level depended on the tumor location and type.

  9. 冠心病患者心外膜脂肪体积及脂肪组织基质蛋白酶2表达、磷脂酶A2水平及意义%Epicardial adipose tissue volume and MMP-2 and PLA2 levels in epicardial adipose tissues of patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    杜文涛; 白净; 智华

    2016-01-01

    Objective To detect the content of epicardial adipose tissue volume ( EATV ) and the levels of matrix metalloproteinase 2 (MMP-2) and phospholipase A2(PLA2) in the epicardial adipose tissues of patients with coronary heart disease ( CHD) and to analyze the significance.Methods A total of 113 patients receiving thoracic surgery were collect-ed, including 67 patients with coronary heart disease (CHD group) and 46 cases with heart valve disease (valvular disease group) .EATV and the nature of the plaque were detected by dual-source CT before surgery to determine whether vascular positive remodeling happened.Then, epicardial adipose tissue ( EAT) and intrathoracic adipose tissue ( TAT) were collect-ed.MMP-2 mRNA and protein levels were detected by RT-PCR and Western blotting.The PLA2 level was detected by ELISA.Finally, the factors related to vascular positive remodeling were analyzed by the logistic regression.Results The EATV in the CHD group was (128.08 ±45.34) cm3 , and (84.21 ±25.37) cm3 in the valvular disease group.There were respectively 36 and 10 cases of vascular positive remodeling in the two groups (all P<0.01).The MMP-2 mRNA and protein expression levels, PLA2 in EATV of the CHD group were significantly higher than those of the valvular disease group (all P<0.05), but the differences of the above indexes were not statistically significant in the thoracic adipose tis-sues (all P>0.05).EATV, MMP-2, PLA2 and high blood pressure were the independent risk factors for the development of vascular positive remodeling in CHD patients.Conclusions The levels of EATV, MMP-2 and PLA2 in the epicardial adipose tissues of CHD patients were increased.EATV, MMP-2 and PLA2 were the independent risk factors for the devel-opment of vascular positive remodeling in CHD patients.%目的 检测冠心病患者心外膜脂肪体积(EATV)及心外膜脂肪组织基质蛋白酶2(MMP-2)表达、磷脂酶A2(PLA2)水平,分析其意义.方法 选择行心脏手术患者113

  10. PRL-3 promotes the motility, invasion, and metastasis of LoVo colon cancer cells through PRL-3-integrin β1-ERK1/2 and-MMP2 signaling

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    Wu Jian

    2009-11-01

    Full Text Available Abstract Background Phosphatase of regenerating liver-3 (PRL-3 plays a causative role in tumor metastasis, but the underlying mechanisms are not well understood. In our previous study, we observed that PRL-3 could decrease tyrosine phosphorylation of integrin β1 and enhance activation of ERK1/2 in HEK293 cells. Herein we aim to explore the association of PRL-3 with integrin β1 signaling and its functional implications in motility, invasion, and metastasis of colon cancer cell LoVo. Methods Transwell chamber assay and nude mouse model were used to study motility and invasion, and metastsis of LoVo colon cancer cells, respectively. Knockdown of integrin β1 by siRNA or lentivirus were detected with Western blot and RT-PCR. The effect of PRL-3 on integrin β1, ERK1/2, and MMPs that mediate motility, invasion, and metastasis were measured by Western blot, immunofluorencence, co-immunoprecipitation and zymographic assays. Results We demonstrated that PRL-3 associated with integrin β1 and its expression was positively correlated with ERK1/2 phosphorylation in colon cancer tissues. Depletion of integrin β1 with siRNA, not only abrogated the activation of ERK1/2 stimulated by PRL-3, but also abolished PRL-3-induced motility and invasion of LoVo cells in vitro. Similarly, inhibition of ERK1/2 phosphorylation with U0126 or MMP activity with GM6001 also impaired PRL-3-induced invasion. In addition, PRL-3 promoted gelatinolytic activity of MMP2, and this stimulation correlated with decreased TIMP2 expression. Moreover, PRL-3-stimulated lung metastasis of LoVo cells in a nude mouse model was inhibited when integrin β1 expression was interfered with shRNA. Conclusion Our results suggest that PRL-3's roles in motility, invasion, and metastasis in colon cancer are critically controlled by the integrin β1-ERK1/2-MMP2 signaling.

  11. Matrix Metalloproteinase 2 (MMP-2) Plays a Critical Role in the Softening of Common Carp Muscle during Chilled Storage by Degradation of Type I and V Collagens.

    Science.gov (United States)

    Xu, Chao; Wang, Cheng; Cai, Qiu-Feng; Zhang, Qian; Weng, Ling; Liu, Guang-Ming; Su, Wen-Jin; Cao, Min-Jie

    2015-12-30

    Matrix metalloproteinases (MMPs) are proposed to play important roles in the degradation of collagens, thus causing the post-mortem softening of fish muscle, although the specific mechanism remains largely unresolved. Previously, we reported the existence of gelatinase-like proteinases in common carp (Cyprinus carpio) muscle. The primary structures of these proteinases, however, have never been investigated. In the present study, two MMPs with molecular masses of 66 and 65 kDa were purified to homogeneity from common carp muscle by ammonium sulfate fractionation and a series of column chromatographies. Matrix-assisted laser desorption/ionization-tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS/MS) analysis indicated that they are completely identical to MMP-2 from common carp. During chilled storage of common carp at 4 °C, the enzymatic activity of MMP-2 increased to 212% in 12 h while the texture profile increased over the first 2 h and gradually decreased. On the other hand, type V collagen was purified to homogeneity and a specific polyclonal antibody against this protein was prepared. Both type I and V collagens were effectively hydrolyzed by MMP-2 at 30 °C and even at 4 °C. Furthermore, injection of metalloproteinase proteinase inhibitor EDTA into the blood vessel of live common carp suppressed post-mortem tenderization significantly. All of these results confirmed that MMP-2 is a major proteinase responsible for the degradation of collagens, resulting in the softening of fish muscle during chilled storage.

  12. The Research Progress of CD147 and MMP-2 in Breast Cancer%CD147和MMP-2在乳腺癌中的研究进展

    Institute of Scientific and Technical Information of China (English)

    崔凌志

    2012-01-01

    基质金属蛋白酶(MMPs)是一类锌离子依赖内肽酶,在恶性肿瘤的侵袭和转移中发挥重要作用,并参与着细胞外基质和基底膜的降解;CD147(EMMPRIN-细胞外基质金属蛋白酶诱导因子)参与恶性肿瘤的侵润转移过程.近期有研究证实CD147在乳腺癌的浸润转移中发挥重要作用.本文旨在对于基质金属蛋白酶家族中的MMP-2及其诱导因子CD147在乳腺癌及肿瘤周围组织中的作用的最新研究作一综述.

  13. The relationship between the first episode of wheezing and matrix metalloproteinases-9 and MMP-2 and tissue inhibitors of MMP-1 levels in preterm infants

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    Rabia Gonul Sezer

    2013-01-01

    Full Text Available Aims: Matrix metalloproteinases (MMP have been associated with neonatal lung morbidity and MMP dysregulation contributes to the pathology of chronic and acute lung disorders. Most of the previous studies were performed in the 1 st weeks of life of the preterm newborns. There are no data on the serum levels of MMP-2, MMP-9 or tissue inhibitors of matrix metalloproteinases (TIMP-1 from preterm infants recovering from lung morbidities. We aimed to compare MMP-2, MMP-9 and TIMP-1 levels in preterm and term infants hospitalized with their first episode of wheezing. Methods: We prospectively evaluated 18 preterm infants with a history of chronic lung disease, respiratory distress syndrome or oxygen therapy and 14 age- and sex-matched term infants who were admitted for a first episode of wheezing. We quantified total serum concentrations of MMP-2, MMP-9 and TIMP-1 to assess whether these serum markers levels were associated with the first episode of wheezing in infants with a history of oxygen therapy during the neonatal period. Results: Upon hospitalization, MMP-2 and TIMP-1 levels were higher in preterm infants than in term infants. In contrast, there was no significant relationship between MMP-9 levels or the MMP-9/TIMP-1 ratio between preterm and term infants. The area under the receiver operating characteristic curve for MMP-2 was 0.70 (95% confidence interval [CI] 0.51-0.89. The area under the curve for TIMP-1 was 0.78 (95% CI 0.61-0.94. MMP-9, MMP-2 and TIMP-1 levels did not correlate with gestational age, gender or severity of wheezing. Conclusion: The negative proportion of MMP-9 to TIMP-1 that we detected in term infants was not present in preterm infants. The balance of MMP-9 to TIMP-1 may have been disrupted by lung damage in the premature infants. Overproduction of MMP-2 and TIMP-1 in the serum may be associated with the pathogenesis of wheezing in preterm infants.

  14. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis

    Science.gov (United States)

    Sampieri, Clara Luz; de la Peña, Sol; Ochoa-Lara, Mariana; Zenteno-Cuevas, Roberto; León-Córdoba, Kenneth

    2010-01-01

    AIM: To assess expression of matrix metalloproteinases 2 (MMP2) and MMP9 in gastric cancer, superficial gastritis and normal mucosa, and to measure metalloproteinase activity. METHODS: MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction. Normalization was carried out using three different factors. Proteins were analyzed by quantitative gelatin zymography (qGZ). RESULTS: 18S ribosomal RNA (18SRNA) was very highly expressed, while hypoxanthine ribosyltransferase-1 (HPRT-1) was moderately expressed. MMP2 was highly expressed, while MMP9 was not detected or lowly expressed in normal tissues, moderately or highly expressed in gastritis and highly expressed in cancer. Relative expression of 18SRNA and HPRT-1 showed no significant differences. Significant differences in MMP2 and MMP9 were found between cancer and normal tissue, but not between gastritis and normal tissue. Absolute quantification of MMP9 echoed this pattern, but differential expression of MMP2 proved conflictive. Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2, total MMP-9, 250 and 110 kDa bands. CONCLUSION: MMP9 expression is enhanced in gastric cancer compared to normal mucosa; interpretation of differential expression of MMP2 is difficult to establish. PMID:20333791

  15. Amlodipine inhibits matrix metalloproteinases expression and secretion in mouse macrophage

    Institute of Scientific and Technical Information of China (English)

    Yamin CAO; Shiwen WANG; Haiyun WU

    2005-01-01

    To investigate whether the calcium channel blocker amlodipine could inhibit macrophage matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression and secretion. Methods Peritoneal macrophages were isolated from BALB/C mice and incubated with low (5μg/L), middle (15μg/L) and high (305μg/L) concentrations of amlodipine, or in the medium alone (controls) for 24 hours, and the expression and secretion of MMP-2 and MM-9 of the cells were analyzed by RT-PCR and gelatin zymography. Results Compared with controls, amlodipine at low concentration had no significant effects on the expression and secretion of either MMP-2 and MMP-9 (P>0.05);at middle concentrationit it could inhibited MMP-2 and MMP-9 expressions completely and significantly reduced the secretion of MMP-9 (P<0.05); but it had no effect on the secretion of MMP-2. At high concentration it also inhibited MMP-2 and MMP-9 expression completely. Conclusion Amlodipine at 15 ìg/L inhibited the expression of MMP-2 and MMP-9 and reduced the secretion of MMP-9, suggesting that amlodipine may stabilize atherosclerotic plaque.

  16. Study on the correlation of MMP-2 and Hyp levels in the synovial fluid with the lesion degree in patients with TMD

    Institute of Scientific and Technical Information of China (English)

    Xiao-Huan Liao

    2016-01-01

    Objective:To explore the correlation of MMP-2 and Hyp levels in the synovial fluid with the lesion degree in patients with TMD.Methods: The clinical materials of 89 cases with TMD (97 sides) who were admitted in our hospital from December, 2010 to December, 2013 were retrospectively analyzed. According to the diagnostic results of clinical examinations and imaging examinations, 37 sides with structural disorders were served as the disorder group, 32 sides with osteoarthropathy were served as the joint disease group, and 28 sides with joint inflammation were served as the inflammation group. While 25 healthy individuals who came for physical examinations were served as the control group. The double-antibody sandwich ELISA was used to detect the levels of MMP-2 and Hyp in the synovial fluids, and their correlations with the lesion degree were analyzed.Results:The comparison of MMP-2 level among the four groups was statistically significant; the comparison between the disorder group and joint disease group was not statistically significant; the comparison between the inflammation group and other three groups was statistically significant; while MMP-2 level in the 3 groups of TMD was significantly higher than that in the control group. The comparison of Hyp level among the four groups was statistically significant; the comparison between the inflammation group and the joint disease group was statistically significant; while Hyp level in the 3 groups of TMD was significantly higher than that in the control group.Conclusions:MMP-2 and Hyp levels in the synovial fluids are different in TMD patients, are closely associated with the pathological damage, and can be served as an effective biochemical indicator in the diagnosis of lesion degree of TMD.

  17. 子宫内膜腺癌组织中CD147、MMP-2的表达变化及意义

    Institute of Scientific and Technical Information of China (English)

    郭哲

    2011-01-01

    目的 观察子宫内膜腺癌组织中CD147、基质金属蛋白酶2(MMP2)的表达变化,并探讨其临床意义.方法 采用免疫组化SP法检测53例子宫内膜腺癌(A组)、35例子宫内膜增殖症(B组)及19例增生期子宫内膜(C组)组织中的CD147、MMP-2蛋白.结果 A组CD147、MMP2蛋白阳性表达44、49例,B组分别为16、20例,C组分别为7、9例;各组间比较,P均<0.05.CD147蛋白表达与子宫内膜癌组织分级有关(P<0.05).子宫内膜腺癌组织中CD147和MMP2蛋白表达呈正相关(r=0.441,P<0.01).结论 子宫内膜腺癌组织中CD147、MMP2的表达增高,二者在子宫内膜腺癌的发展恶化、侵袭和转移中发挥重要作用.

  18. Value of serum MMP-7 conbined MMP-2 in predicting the prognosis of patients with liver cancer and the relationship between them and infiltration, metastasis%血清MMP-7和MMP-2联合肝癌预测预后的价值及其与肝癌浸润转移的关系

    Institute of Scientific and Technical Information of China (English)

    邓少源

    2016-01-01

    目的:探讨肝癌患者血清MMP-7和MMP-2水平联合预测预后的价值及其与肝癌浸润转移的关系.方法:选择原发性肝癌患者125例为观察组,30例同期良性肝脏疾病患者为对照组.检测两组血清MMP-7和MMP-2水平,分析观察组肝癌浸润程度、淋巴结转移情况、3年生存率以及血清MMP-7和MMP-2水平与肝癌浸润、转移及预后的关系.结果:观察组治疗前后的血清MMP-7和MMP-2水平均高于对照组.与治疗前比较,治疗后观察组血清MMP-7和MMP-2水平均降低(P<0.05).观察组浸润超过包膜、出现淋巴结转移和死亡患者血清MMP-7和MMP-2水平均高于未浸润包膜、无淋巴结转移和存活患者(P<0.05).观察组血清MMP-7和MMP-2水平与其浸润超过包膜率、淋巴结转移率和3年生存率均相关,且两者联合预测肝癌预后的价值良好.结论:肝癌患者血清MMP-7和MMP-2水平较高,且与肝癌浸润、转移及预后相关,MMP-7和MMP-2联合预测预后的价值良好,可用于肝癌浸润、转移及预后评估.

  19. 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.

  20. 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.

  1. Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer.

    NARCIS (Netherlands)

    Jagt, M. van der; Sweep, C.G.J.; Waas, E.T.; Hendriks, T.; Ruers, T.J.M.; Merry, A.H.; Wobbes, Th.; Span, P.N.

    2006-01-01

    mRNA, and latent and active levels MMP-2 and -9 were higher in tumor tissue compared to normal tissue from 63 patients with colorectal cancer, whereas RECK and EMMPRIN levels were lower. Correlations between mRNA, latent, and active MMP were particular high for MMP-2 in tumor tissue (R(s)=0.6-0.8, P

  2. The effect of hormone in treating idiopathic pulmonary interstitial fibrosis on the levels of MMP-2,TIMP-1 and type Ⅳ collagen%激素治疗对特发性肺间质纤维化患者血清MMP-2和TIMP-1及Ⅳ型胶原水平的影响

    Institute of Scientific and Technical Information of China (English)

    李繁丽; 戈艳蕾; 刘聪辉; 王红阳

    2012-01-01

    目的 观察特发性肺间质纤维化(IPF)患者血清基质金属蛋白酶-2(MMP-2)、基质金属蛋白抑制因子(TIMP-1)及Ⅳ型胶原(Ⅳ-C)含量及激素治疗前后对其影响.方法 选择50例IPF患者及15例健康对照人群,测定IPF患者及对照组血清MMP-2、TIMP-1及Ⅳ-C水平;IPF患者予口服激素治疗,据IPF患者治疗后临床症状缓解程度,判定为治疗有效组或无效组,比较2组治疗前后血清MMP-2、TIMP-1及Ⅳ-C水平变化.结果 IPF患者治疗前血清MMP-2、TIMP-1及Ⅳ-C含量高于对照组(P0.05),无效组血清MMP-2、TIMP-1及Ⅳ-C水平治疗前后变化差异无统计学意义(P>0.05).结论 治疗前血清MMP-2高可以提示对激素治疗反映较好,血清TIMP-1及Ⅳ-C高,提示激素治疗疗效较差.%Objective To investigate the effect of hormone therapy on the serum levels of matrix matalloproteinase-2 ( MMP-2 ), tissue inhibitor of metalloproteinase-1 ( TIMP-1 ) and type IV collagen in patients with idiopathic pulmonary interstitial fibrosis ( IPF ). Methods The 50 patients with IPF and 15 healthy subjects ( control group ) were enrolled in the study, and the serum levels of MMP-2, TIMP-1 and type IV collagen were detected for all the patients and healthy subjects. The patients were treated by oral hormones, then the patients were divided into efficiency group and no efficiency group according to the relief extent of clinical symptoms, and the changes of serum levels of MMP-2, TIMP-1 and type IV collagen before and after treatment were detected and compared. Results Before treatment the serum levels of MMP-2,TIMP-1 and type IV collagen in patients with IPF were significantly higher than those of healthy subjects ( P 0. 05 ), nor were the serum levels of MMP-2,TIMP-1 and type IV collagen before treatment and after treatment in no efficiency group ( P > 0.05 ). Conclusion The higher levels of serum MMP-2 in patients with IPF may suggest that the therapeutic effect of hormone is better

  3. 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.

  4. Matrix Metalloproteinases Expression in Choroidal Neovascular Membranes

    Institute of Scientific and Technical Information of China (English)

    Jun Zeng; Deyong Jiang; Xiangping Liu; Xiaohua Zhu; Luosheng Tang

    2004-01-01

    Purpose: To investigate the expression of matrix metalloproteinases (MMPs) in choroidal neovascular membranes with age-related macular degeneration (AMD).Methods: Seventeen choroidal neovascular membranes surgically removed from AMD patients with pars plana vitrectomy and subretinal membranes peeling were investigated.The expression of MMP-2 and MMP-9 was determined with immunohistochemical technique.Results: Immunohistochemistry staining in choroidal neovascular membranes for MMP2 and MMP-9 was observed in 17 specimens. There was no detective of MMP-2 and MMP-9 in normal retinas.Conclusions: MMP-2 and MMP-9 were found in choroidal neovascular membranes, may degrade the Bruch membrane and be associated with the perforation of new vessels into Bruch membrane, involving a basic pathogenic process of AMD.

  5. Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Ming-Chao Bi

    2016-01-01

    Full Text Available Zeaxanthin at nonlethal dosages (3–10 μM significantly inhibited the cell migration of cultured uveal melanoma cells (C918 cell line as determined by wound healing assay and Boyden chamber assay. Matrigel invasion assay showed that cell invasion of uveal melanoma cells could be significantly inhibited by zeaxanthin. Secretion of MMP-2 by melanoma cells was significantly inhibited by zeaxanthin in a dose-dependent manner as measured by ELISA kit. Zeaxanthin also significantly inhibited the NF-κB levels in nuclear extracts of the UM cells, which is the upstream of the MMP-2 secretion. These results suggest that zeaxanthin might be a potentially therapeutic approach in the prevention of metastasis in uveal melanoma.

  6. 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

  7. Evaluation of a Triple-Helical Peptide with Quenched Fluorophores for Optical Imaging of MMP-2 and MMP-9 Proteolytic Activity

    Directory of Open Access Journals (Sweden)

    Xuan Zhang

    2014-06-01

    Full Text Available Matrix metalloproteinases (MMP 2 and 9, the gelatinases, have consistently been associated with tumor progression. The development of gelatinase-specific probes will be critical for identifying in vivo gelatinoic activity to understand the molecular role of the gelatinases in tumor development. Recently, a self-assembling homotrimeric triple-helical peptide (THP, incorporating a sequence from type V collagen, with high substrate specificity to the gelatinases has been developed. To determine whether this THP would be suitable for imaging protease activity, 5-carboxyfluorescein (5FAM was conjugated, resulting in 5FAM3-THP and 5FAM6-THP, which were quenched up to 50%. 5FAM6-THP hydrolysis by MMP-2 and MMP-9 displayed kcat/KM values of 1.5 × 104 and 5.4 × 103 M−1 s−1, respectively. Additionally 5FAM6-THP visualized gelatinase activity in gelatinase positive HT-1080 cells, but not in gelatinase negative MCF-7 cells. Furthermore, the fluorescence in the HT-1080 cells was greatly attenuated by the addition of a MMP-2 and MMP-9 inhibitor, SB-3CT, indicating that the observed fluorescence release was mediated by gelatinase proteolysis and not non-specific proteolysis of the THPs. These results demonstrate that THPs fully substituted with fluorophores maintain their substrate specificity to the gelatinases in human cancer cells and may be useful in in vivo molecular imaging of gelatinase activity.

  8. Direct inhibition of matrix metalloproteinase-2 (MMP-2) by (-)-epigallocatechin-3-gallate: A possible role for the fibronectin type II repeats.

    Science.gov (United States)

    Jha, Shalinee; Kanaujia, Shankar Prasad; Limaye, Anil M

    2016-11-15

    Matrix metalloproteinases (MMPs) -2 and -9, also called gelatinases, constitute a distinct subgroup within the MMP family of extracellular matrix remodeling proteases. Gelatinases are implicated in tumor cell invasion and metastasis, and are attractive therapeutic targets. Several synthetic small molecule inhibitors of MMPs developed till date have failed in clinical trials. This has prompted explorations into the gamut of dietary compounds and nutraceuticals for specific inhibitors of MMPs with desirable properties. (-)-epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, is popular as a potential chemotherapeutic agent with demonstrable anti-metastatic and MMP inhibitory activities. Here, we have addressed the mechanism of EGCG-mediated inhibition of MMP-2 using in silico molecular docking approach. We show for the first time that EGCG targets the fibronectin type II repeat regions 1 and 3 of MMP-2, binds amino acids that constitute the exosite of this enzyme and hinders proper positioning of the substrate. This study offers a novel insight into the inhibition of MMP-2 by EGCG and presents a starting point for development of novel therapeutic molecules that can specifically target the gelatinases.

  9. Basement membrane zone remodeling during appendageal development in human fetal skin. The absence of type VII collagen is associated with gelatinase-A (MMP2) activity.

    Science.gov (United States)

    Karelina, T V; Bannikov, G A; Eisen, A Z

    2000-02-01

    Epithelial cell adhesion, migration, and differentiation are controlled by interactions at the basement membrane zone (BMZ). Type VII collagen is the major collagenous component of anchoring fibrils that are essential for the attachment of the epidermis to the dermis. Gelatinase A (MMP-2) is believed to be necessary for the degradation of type VII collagen. In this study we have examined the in vivo distribution of type VII collagen and gelatinase A (Gel A) in the developing human epidermis and its appendages. At 13-15 wk of gestation a marked decrease in type VII collagen immunoreactivity was seen in the BMZ surrounding invading appendageal buds; however, type VII collagen mRNA was strongly expressed in the budding epidermal keratinocytes adjacent to the BMZ. At these stages, Gel A-positive mesenchymal-like cells were found scattered throughout the stroma with numerous Gel A-containing cells in direct contact with the developing appendageal buds. In situ zymography was used to show Gel A-activity in vivo. Gel A-mediated lysis was present at the interface between the appendageal buds and the underlying BMZ. By 20-25 wk of gestational age, immunostaining for type VII collagen protein was absent from the BMZ surrounding the distal portion of invading appendageal epithelial cords of both hair follicles and sweat glands. In contrast, type VII collagen mRNA was present in the basal keratinocytes adjacent to the BMZ surrounding the distal portion of these invading appendageal epithelial cords. At these stages Gel A-positive cells were present in the stroma directly adjacent to the distal portion of developing appendageal cords that lacked type VII collagen. In situ zymography showed zones of Gel A-mediated stromal lysis at the distal portion of developing appendageal cords. Interestingly, no differences were seen in the distribution of type IV collagen in the BMZ of both budding and resting fetal epidermis. These observations suggest that the absence of type VII collagen

  10. QM/MM Studies of the Matrix Metalloproteinase 2 (MMP2) Inhibition Mechanism of (S)-SB-3CT and its Oxirane Analogue.

    Science.gov (United States)

    Zhou, Jia; Tao, Peng; Fisher, Jed F; Shi, Qicun; Mobashery, Shahriar; Schlegel, H Bernhard

    2010-11-09

    SB-3CT, (4-phenoxyphenylsulfonyl)methylthiirane, is a potent, mechanism-based inhibitor of the gelatinase sub-class of the matrix metalloproteinase (MMP) family of zinc proteases. The gelatinase MMPs are unusual in that there are several examples where both enantiomers of a racemic inhibitor have comparable inhibitory abilities. SB-3CT is one such example. Here, the inhibition mechanism of the MMP2 gelatinase by the (S)-SB-3CT enantiomer and its oxirane analogue is examined computationally, and compared to the mechanism of (R)-SB-3CT. Inhibition of MMP2 by (R)-SB-3CT was shown previously to involve enzyme-catalyzed C-H deprotonation adjacent to the sulfone, with concomitant opening by β-elimination of the sulfur of the three-membered thiirane ring. Similarly to the R enantiomer, (S)-SB-3CT was docked into the active site of MMP2, followed by molecular dynamics simulation to prepare the complex for combined quantum mechanics and molecular mechanics (QM/MM) calculations. QM/MM calculations with B3LYP/6-311+G(d,p) for the QM part (46 atoms) and the AMBER force field for the MM part were used to compare the reaction of (S)-SB-3CT and its oxirane analogue in the active site of MMP2 (9208 atoms). These calculations show that the barrier for the proton abstraction coupled ring opening reaction of (S)-SB-3CT in the MMP2 active site is 4.4 kcal/mol lower than its oxirane analogue, and the ring opening reaction energy of (S)-SB-3CT is only 1.6 kcal/mol less exothermic than its oxirane analogue. Calculations also show that the protonation of the ring-opened products by water is thermodynamically much more favorable for the alkoxide obtained from the oxirane, than for the thiolate obtained from the thiirane. In contrast to (R)-SB-3CT and the R-oxirane analogue, the double bonds of the ring-opened products of (S)-SB-3CT and its S-oxirane analogue have the cis-configuration. Vibrational frequency and intrinsic reaction path calculations on a reduced size QM/MM model (2747 atoms

  11. 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-9、MMP-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.

  12. 乳腺癌患者手术治疗前后血清CA153、IL-8、MMP-2和TIMP-2水平检测的临床意义%Clinical significance of serum level of CA153,IL-8,MMP-2,TIMP-2 changes of patients with breast cancer before and after surgical treatment

    Institute of Scientific and Technical Information of China (English)

    王仲

    2013-01-01

    目的 探讨乳腺癌患者手术治疗前后血清糖类抗原-153 (CA153)、白细胞介素-8(IL-8)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-2组织抑制剂(TIMP-2)的含量及临床价值.方法 应用放射免疫分析法和酶联法对34例乳腺癌患者(观察组)进行手术治疗前后血清CA153、IL-8和MMP-2、TIMP-2水平的检测,并与35例正常对照组作比较.结果 观察组在手术前血清CA153、IL-8、MMP-2、TIMP-2均显著高于对照组(P<0.01);手术后3个月未复发的29例其血清CA153、IL-8和MMP-2、TIMP-2水平下降或接近正常,而复发的5例其血清水平又回升到手术前的水平(P<0.01);且血清CA153水平与IL-8、MMP-2 、TIMP-2测定显著相关(r=0.5784、0.4926、0.6011,P<0.01).结论 检测乳腺癌患者手术治疗前后血清CA153、IL-8、MMP-2、TIMP-2水平的变化可作为乳腺癌患者诊断和疗效观察的参数.

  13. Effects of Danggui Buxue Decoction (当归补血汤) on Lipid Peroxidation and MMP-2/9 Activities of Fibrotic Liver in Rats

    Institute of Scientific and Technical Information of China (English)

    陈园; 陈倩; 吕靖; 李凤华; 陶艳艳; 刘成海

    2009-01-01

    Objective:To explore the mechanism of Danggui Buxue Decoction(当归补血汤,DBD) on the liver fibrosis related to hepatic lipid peroxidation and matrix metalloproteinases(MMP) -2/9 activities.Methods: The liver fibrosis in 28 rats was induced by an injection of carbon tetrachloride(CCl_4) and fed with high lipid and low protein diet for 6 weeks,the model rats were randomly divided into the model group and DBD treated group,14 in each group,and another 10 rats as the normal group were observed as well.Rats in the...

  14. Preliminary evidence for a matrix metalloproteinase-2 (MMP-2)-dependent shedding of soluble CD40 ligand (sCD40L) from activated platelets.

    Science.gov (United States)

    Reinboldt, Stephan; Wenzel, Folker; Rauch, Bernhard H; Hohlfeld, Thomas; Grandoch, Maria; Fischer, Jens W; Weber, Artur-Aron

    2009-09-01

    Platelets are the major source of soluble CD40 ligand (sCD40L) in the blood. It has been demonstrated that CD40L is cleaved from the surface of activated platelets to release sCD40L. However, the enzyme involved in sCD40L shedding has not been identified yet. Using a panel of pharmacological inhibitors of serine, cysteine, aspartate, or metalloproteinases, preliminary evidence is presented for the hypothesis that matrix metalloproteinase-2 (MMP-2) might be the protease, primarily responsible for CD40L cleavage from platelet surface.

  15. High glucose enhance expression of matrix metalloproteinase—2 in smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    HAOFeng; YUJin-De

    2003-01-01

    AIM:To investigate the effects of high glucose on expression of matrix metalloproteinase-2(MMP-2) in rat aortic smooth muscle cells and the influence of matrix remodeling on atherogenesis in diabetic patients. METHODS: The smooth muscle cells were cultured from the thoracic aorta of Sprague-Dawley (SD) rat. MMP-2 mRNA was determined by reverse transcriptase-polymerase chain reaction(RT-PCR),MMP-2 protein was measured by Western blotting, and MMP-2 activity in conditioned medium was observed by zymography. RESULTS:In comparison with the control, there was no difference in the expression of MMP-2 when glucose concentration was 1g/L,whereas MMP-2 activity in smooth muscle cells was significantly increased by the glucose 5 g/L(P<0.01). CONCLUSION:High glucose enhanced the expression and activity of MMP-2 in smooth muscle cells, which may provide an explanation for the phenomenon that diabetes patients are prone to have atherosclerotic lesions.

  16. Detection and the clinical significance of serum MMP-2、MMP-3、MMP-9 and TIMP-4 levels in patients with systemic lupus erythematosus%系统性红斑狼疮患者外周血MMP-2、MMP-3、MMP-9和TIMP-4水平的检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    胡亮; 彭奕冰; 王学锋; 巩惠芸

    2012-01-01

    目的:检测系统性红斑狼疮(SLE)患者外周血基质金属蛋白酶(MMP)-2、MMP-3、MMP-9和基质金属蛋白酶组织型抑制因子(TIMP)-4的水平,并探讨其临床意义.方法:采用双抗夹心ELISA法,检测58例SLE患者及30例正常对照者的血清MMP-2、MMP-3、MMP-9和TIMP-4水平.结果:SLE患者血清MMP-3、TIMP-4水平显著高于正常对照者,但其血清MMP-2、MMP-9水平则与正常对照者间无统计学差异.SLE患者的血清MMP-3水平与MMP-2、MMP-9、TIMP-4水平均呈正相关,MMP-9水平与MMP-2水平间亦呈正相关;同时其MMP-2、MMP-3、MMP-9水平与反映肾脏、肝脏及机体免疫状态的多组指标间存在相关性,包括尿素氮、肌酐、尿酸、白蛋白、免疫球蛋白G、免疫球蛋白A、免疫球蛋白M、补体C3和补体C4等;SLE患者中,发生血小板减少者的血清MMP-2、MMP-9水平与血小板正常者相比显著降低.结论:SLE患者外周血MMP-3和TIMP-4水平显著升高.不同MMP间可相互调节,同时也受TIMP-4等TIMP的调节.MMP-2、MMP-3和MMP-9可能参与了SLE患者肾脏和肝脏的病理损害过程.%Objective To detect serum matrix metalloproteinase (MMP)-2, MMP-3, MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-4 levels in patients with systemic lupus erythematosus (SLE) and define its clinical significance. Methods Serum levels of MMP-2, MMP-3, MMP-9 and TIMP-4 were measured by ELISA. Results Levels of MMP-3 and TIMP-4 were significantly higher in SLE patients than those in healthy controls. Positive correlation was found between these MMPs. Serum MMP-2, MMP-3, MMP-9 levels had a correlation with other laboratory results reflecting the condition of kidney, liver and immunity. MMP-2 and MMP-9 levels were decreased in SLE patients having a low platelet count. Conclusins Serum MMP-2 and TIMP-4 levels are significantly higher in patients with SLE. MMP-2, MMP-3 and MMP-9 were regulated by a complicated network. TIMP-4 is involved in this

  17. Effect of IPS e.max Press Ceramic Crown on the Level of MMP-2 in Gingival Crevicular Fluid%IPS e.max Press铸瓷全冠对龈沟液中MMP-2水平的影响

    Institute of Scientific and Technical Information of China (English)

    董蕾; 孙振学; 朱海燕

    2015-01-01

    Objective To observe the ef ects of IPS e.max press ceramic crown on the periodontal tissue of the restored teeth. Methods 79 clinical patients (107 anterior teeth)were selected to be placed by IPS e.max press ceramic crown ,and before and 6 months after rehab,the weight of gingival crevicular fluid (GCF)was mensurated and the level of MMP-2 in GCF was checked by way of enzyme-linked immuno sorbent assay,the result was analyzed. Results The weight of GCF,the level of MMP-2 in GCF after rehab had no significantly statistical dif erence with those before rehab(﹥0.05). Conclusion IPS e.max press ceramic crown has no significantly negative influence on gingival health of the restored teeth. And it is a kind of restoration with favorable biocompatibility.%目的:探讨IPS e.max Pres 铸瓷全冠修复对牙周组织的影响。方法选择IPS e.max Pres 铸瓷全冠修复患者79例107颗患牙,在修复前和修复后6个月,测定龈沟液(GCF)量,并运用采用酶联免疫吸附试验(ELISA)对龈沟液中基质金属蛋白酶-2(MMP-2)水平进行分析。结果修复后GCF量、MMP-2水平与修复前比较差异无统计学意义(﹥0.05)。结论 IPS e.max Pres 铸瓷全冠对牙周组织无明显影响,是一种生物相容性良好的修复方式。

  18. Correlation investigation between levels of MMP-2,MMP-3,MMP-10,TIMP-1 and type 1 diabetes with albuminuria%MMP -2、MMP -3、MMP -10及 TIMP -1与1型糖尿病蛋白尿的相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱于坚

    2016-01-01

    Objective To investigate the correlation between levels of MMP - 2,MMP - 3,MMP - 10,TIMP - 1 and type 1 diabetes with albuminuria. Methods Fourty patients of type 1 diabetes with microalbuminuria or macroalbuminuria were selected in this study(observa-tion group). Meanwhile 40 healthy people for healthy check in the same period were selected as control group. General information and biochemi-cal indices(HbA1c,LDL,TC,MMP - 2,MMP - 3,MMP - 10,TIMP - 1,sVCAM - 1,E - selectin,CRP,IL - 6,TNF - α levels)in two group were compared. Simultaneously,MMP - 2,MMP - 3,MMP - 10,TIMP - 1,sVCAM - 1,E - selectin,CRP,IL - 6,TNF - α levels in patients with microalbuminuria and macroalbuminuria were compared. Respectively analysis MMPs and TIMP - 1 and sVCAM - 1 correlation of E- selectin,CRP,IL - 6,TNF - α. Results ①The levels of HbA1c,LDL,TC,MMP - 2,MMP - 3,MMP - 10,TIMP - 1,sVCAM - 1,E- selectin,CRP,IL - 6,TNF - αlevels in observation group were higher than those in control group,showing statistically significant difference( P 0. 05). ③MMP - 10,TIMP - 1 showed a significant positive correlation with sVCAM - 1and E - selectin( P < 0. 05). And MMP - 2 and MMP - 3 was negatively correlated with E - se-lectin and positively correlated with sVCAM - 1. MMP - 3,MMP - 10,TIMP - 1 displayed significantly positive correlation with CRP,TNF - α, IL - 6( P < 0. 05),but MMP - 2 only showed a significant positive correlation with IL - 6,and no significant correlation with CRP and TNF -α. Conclusion MMP - 2,MMP - 3,MMP - 10 and TIMP - 1 were related with albuminuria in type 1 diabetes - related. With the increased levels of albumin excretion,MMP - 2,MMP - 3,MMP - 10 and TIMP - 1 levels were accordingly increased,suggesting their correlation with the severity of albuminuria in type 1 diabetes.%目的探讨基质金属蛋白酶(MMP)-2、MMP -3、MMP -10及基质金属蛋白酶组织抑制因子(TIMP)-1与1型糖尿病蛋白尿的相关性。方法选择40例1型糖尿病伴微量

  19. Role of MMP-2 and MMP-9 and their natural inhibitors in liver ifbrosis, chronic pancreatitis and non-speciifc inlfammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Jacek Kurzepa; Agnieszka Mądro; Grażyna Czechowska; Joanna Kurzepa; Krzysztof Celiński; Weronika Kazmierak; Maria Słomka

    2014-01-01

    BACKGROUND: There is a growing evidence that matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases) play an important role in the pathogenesis of numerous disorders, especially with inflammatory etiology and extracellular matrix (ECM) remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation. DATA SOURCES: We carried out a PubMed search of Englishlanguage articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases. RESULTS: The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however, reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation. CONCLUSION: The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatorybowel diseases is observed, but the exact role of these enzymes demands further studies.

  20. MMP2 and MMP9 serum levels are associated with favorable outcome in patients with inflammatory breast cancer treated with bevacizumab-based neoadjuvant chemotherapy in the BEVERLY-2 study

    Science.gov (United States)

    Tabouret, Emeline; Bertucci, François; Pierga, Jean-Yves; Petit, Thierry; Levy, Christelle; Ferrero, Jean-Marc; Campone, Mario; Gligorov, Joseph; Lerebours, Florence; Roché, Henri; Bachelot, Thomas; van Laere, Steven; Ueno, Naoto T.; Toiron, Yves; Finetti, Pascal; Birnbaum, Daniel; Borg, Jean-Paul; Viens, Patrice

    2016-01-01

    Purpose Addition of bevacizumab to trastuzumab-based neoadjuvant chemotherapy in HER2-positive inflammatory breast cancer (IBC) was associated with favorable outcome in the BEVERLY-2 phase II trial. Circulating levels of matrix metalloproteinases (MMP) 2 and 9 were correlated to high response rate and prolonged survival in high-grade glioma treated with bevacizumab. We examined the prognostic impact of MMP2 and MMP9 serum levels in BEVERLY-2 patients. Experimental design MMP2 and MMP9 serum levels were assessed using ELISA at baseline and before surgery in 45/52 available samples. Correlations were tested with pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Results Baseline (b) MMP2 and MMP9 serum levels were independent from patient characteristics and circulating tumor or endothelial cells, and were not correlated to pCR. High bMMP2 was correlated to better DFS (p=0.001) and OS (p=0.032), while low bMMP9 was correlated to better OS (p=0.022) and tended to be associated with longer DFS (p=0.071). In multivariate analyses, bMMP2 (p=0.003, Hazard Ratio [HR]: 0.115) and bMMP9 (p=0.041, HR: 3.511) remained correlated to DFS. As continuous variables, bMMP2 was associated with relapse (p=0.002) and death (p=0.049), while bMMP9 was associated with death (p=0.035). During treatment, significant increase in MMP2 and decrease in MMP9 levels (p<0.001 for both) were observed in 100% and 87% of patients respectively. Conclusions High bMMP2 and low bMMP9 serum levels were associated with better survival in HER2-positive IBC patients treated with bevacizumab- and trastuzumab-based neoadjuvant chemotherapy. Their predictive value of bevacizumab benefit should be evaluated in a randomized trial. PMID:26921265

  1. Expression and characterization of common carp (Cyprinus carpio) matrix metalloproteinase-2 and its activity against type I collagen.

    Science.gov (United States)

    Wang, Ci; Zhan, Chun-Lan; Cai, Qiu-Feng; Du, Cui-Hong; Liu, Guang-Ming; Su, Wen-Jin; Cao, Min-Jie

    2014-05-10

    Matrix metalloproteinases (MMPs) play essential roles in the metabolism of animal collagen while few reports are available for MMPs in aquatic animals. In this study, we report the complete sequence of matrix metalloproteinase-2 (MMP-2) gene from common carp (Cyprinus carpio) skeletal muscle. The full-length cDNA of MMP-2 was 2792bp which contains an open reading frame of 1974bp, corresponding to a protein of 657 amino acid residues. Based on the structural feature of MMP-2, the gene of the catalytic domain containing 351 amino acid residues was cloned and expressed in Escherichia coli. SDS-PAGE showed that the truncated recombinant MMP-2 (trMMP-2) with molecular mass of approximately 38kDa was in the form of inclusion body. The trMMP-2 was further purified by immobilized metal ion affinity chromatography. After renaturation, similar to native MMP-2, the trMMP-2 exhibited high hydrolyzing activity toward gelatin as appeared on gelatin zymography and optimal activity was at pH 8.0 and 40°C. The activity of the trMMP-2 was completely suppressed by metalloproteinase inhibitors, including EDTA, EGTA and 1,10-phenanthroline while other proteinase inhibitors did not show any inhibitory effect. Divalent metal ion Ca(2+) was necessary for the gelatinolytic activity, suggesting it is a calcium-dependent metalloproteinase. Moreover, the trMMP-2 effectively hydrolyzed native type I collagen at 37°C and even at 4°C, implying its potential application value as a collagenase for preparation of biologically active oligopeptides.

  2. 基质金属蛋白酶及其抑制物在正常和异位子宫内膜中的表达%The expression of matrix metalloproteinase and its inhibitor in eutopic and ectopic endometria

    Institute of Scientific and Technical Information of China (English)

    王丽; 李东爽; 郭雪霏

    2011-01-01

    目的研究基质金属蛋白酶2、9(Matrix metalloprotein MMP2、MMP9)和基质金属蛋白酶抑制剂1(TIMP1)与子宫内膜异位症的相关性.方法采用免疫组化方法检测MMP2、MMP9、TIMP1蛋白的表达.结果 异位子宫内膜标本中MMP2表达增强,MMP9、TIMP1的表达在各组之间差异无统计学意义.结论 MMP2可能与子宫内膜异位症的发生密切相关.%Objective To evaluate the expression and localization of matrix metalloproteinase2、9 (MMP2、MMP9)and tissue inhibitor of matrix metollaproteinase 1 (TIMP1) in endometriosis.Method The expression of MMP2、MMP9 protein on paraffin embeded tissues was determined by immunohistochemical analysis.Results Endometriotic tissues showed statisticaly stronger MMP2 protein compared with eutopic endometria (P < 0.05).MMP9、TIMP1 expresion were same in eutopic endometria and ectopic endometria.Conclusion Compared to eutopic endometrium,ectopic endometrium has a higher capacity to produce MMP2.

  3. 姜黄素对心肌梗死后血流动力学及心肌基质金属蛋白酶-2表达的影响%Effects of curcumin on MMP-2 and hemodynamics following myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    贺兆发; 刘春辉; 刘聪辉; 卢均坤; 李奕红; 范蕾; 刘畅; 张丽

    2015-01-01

    Objective The present study was designed to examine the effects of curcumin on hemodynamics and ma-trix metallo proteinases-2 ( MMP-2 ) expression in myocardial infarction rats. Method 70 cases Sprague-Dawley healthy adult male rats (250~300g) were randomly divided into sham operation group (n=15) and miocardial in-farction group ( MI, n=55 ) . The mode of operation was that the line in left anterior descending coronary artery threading and knotting but not to block the blood flow had used for sham operation group. MI group was established by ligation of left anterior descending branch of coronary artery and the sham operation group ( sham) rats underwent the same procedure without ligation. 24 hours later, the MI group was further sub-divided into 3 groups: control group, solvent group and curcumin group. The solvent group was treated with only solvent( a blend which blend Po-lyethylene glycol, alcohol and water)and curcumin group was intraperitoneally administered with curumin at 100mg/kg/d for 28 days. MP150 type multichannel physiological functions signal collection processing system was used to test left ventricular end diastolic pressure ( LVDEP) , systolic pressure ( SYS) , maximum change in pressure over the cycle (dp/dtmax), minimum change in pressure over the cycle (dp/dtmin) and mean blood pressure (MBP). HE stalning was employed to detect the morphological changes of cardiomyocytes. Moreover, the expression of MMP-2 protein in the myocardium of the rats was tested by immunohistochemical technique. Result SYS, dp/dtmax and dp/dtmin were significantly increased while the LVDEP decreased in the curcumin group compared with control (P<0. 05). Immunohistochemistry revealed a decrease in expression of MMP2 in curcumin group compared to con-tral and solvent groups(P<0. 05). HE stalning revealed that some normal cardiac myocytes were disappeared after MI, and were replaced by collagens. Conclusion Our study revealed that curcumin ameliorated hemodynamics and

  4. The coordinate alteration of actin cytoskeleton, CD44 and matrix metalloproteinase-2 in the metastasis of breast cancer cells%转移相关分子链Actin-CD44-MMP-2在乳腺癌转移实验中的改变

    Institute of Scientific and Technical Information of China (English)

    赵威; 韩海勃; 林仲翔; 张志谦

    2011-01-01

    Objective To study the roles of actin and associated molecules in the control of human breast cancer cell malignant behaviors in vitro and in vivo.Methods A highly metastatic human breast cancer cell line BICR-H1 was compared with another breast cancer cell line MCF-7, which was well differentiated and non-metastatic.Western blot, immunofluorescence, gelatin zymography analysis and a chick embryonic chorioallantoic membrane (CAM) assay were used in this research.5~30 μg cisplatin or MMP-2 C terminal PEX domain were injected i.v.in CAM.Results BICR - H 1 expressed high level of CD44, which was closely associated with actin aggregates at the bottom side of attached cells.It was also shown with MMP-2 activity.On the contrary, MCF-7 cells showed weak disruption of actin cytoskeleton structures and a few actin aggregates.It expressed low or minimal level of CD44 and MMP-2.The expression of CD44 was down-regulated in cisplatin-treated BICR-H1 cells, and the activity of MMP-2 was also decreased upon PEX treatment.Both cell lines could form tumors in CAM, but only BICR-H1 cells could metastasize to distant tissues.Cisplatin inhibited the growth of BICR-H1 and MCF-7 cells in a time and dose dependent manner in CAM.The lung metastatic foci of BICR-H1 cells treated with 30 μg cisplatin were reduced from 30 ± 15/embryo (PBS group) to 8 ± 6/embryo, and the same dose of PEX could completely inhibit BICR-H1 metastasis.Conclusion It is concluded that actin cytoskeleton, CD44 and MMP-2 (ACM) molecular linkage is associated with breast cancer metastatic phenotypes, and both cisplatin and PEX can interfere with the ACM molecular linkage, resulting in the suppression of both tumor growth and metastasis.%目的 研究乳腺癌转移相关的分子机制及抑制体内外转移的作用和机制.方法 选择高、低转移性乳腺癌细胞系BICR-H1和MCF-7,用明胶底物非变性电泳分析法、Western blot和免疫荧光染色等方法,观察肌动蛋白、CD44

  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活

  6. 多发性骨髓瘤患者MMP-2和MMP-9在塑料包埋骨髓活检组织的表达

    Institute of Scientific and Technical Information of China (English)

    韦中玲; 汪兴洪; 黄东平

    2008-01-01

    目的:通过观察基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)在多发性骨髓瘤(MM)患者塑料包埋骨髓活检块中的表达,探讨MM的发病机制和预后。方法:用SP免疫组化法检测MM患者骨髓活检组织塑料包埋块中MMP-2和MMP-9的表达。结果:MMP-2和MMP-9在MM组中高表达,在对照组中低表达,P〈0.05差异具有统计学意义;与MMP-9表达阴性患者相比,高表达MMP-9的患者骨损害明显,白蛋白低,β2微球蛋白高。结论:MMP-2和MMP-9在MM发病中具有促进作用,MMP-9可能参与MM骨病的发生,提示预后不良。

  7. Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Jin Man Kim; Sang Wook Kang; Su-Mi Shin; Duck Su Kim; Kyong-Kyu Choi; Eun-Cheol Kim; Sun-Young Kim

    2014-01-01

    All-trans retinoic acid (ATRA) inhibits matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fibroblasts, skin fibroblasts, bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells (HDPCs). The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and-9 in HDPCs. The productions and messenger RNA (mRNA) expressions of MMP-2 and-9 were accessed by gelatin zymography and real-time polymerase chain reaction (PCR), respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 mmol?L21 ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs, which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.

  8. 异丙酚对肺气肿大鼠 MMP-2和 MMP-9的影响%Effect of propofol on matrix metaloproteinase-2 and matrix metaloproteinase-9 in emphysema in rats

    Institute of Scientific and Technical Information of China (English)

    闵振兴; 陈丽辉; 黄漫

    2013-01-01

      Objective: To study the Effect of propofol on matrix metaloproteinase-2 and matrix metaloproteinase-9 in emphysema in rats and its clinical significance. Methods:30 Wistar rats, weighing 200 to 250 g, male or female. Were randomly divided into three groups: smoking plus Klebsiela pneumoniae infection group (S group), propofol treatment group P group and the control group (C group). (N = 10). S Group and P Group were infected Klebsiela pneumoniae contamination by nasal inhalation 1-2 times a week, each time each animal 0.1ml, a total of 10 weeks; both groups were inhaled cigarettes through the catheter each 2h, 5 times a week for 16 C Group animals were no smoke, while the culture medium instead of bacteria inhaled.RESULTS: Under light microscope, C group lung tissue was normal, But S group showed severe structural damage, alveolar colapse, interstitial pulmonary edema, hemorrhage, inflammatory cel infiltration, showed obvious signs of emphysema changes. Pathological changes of the P group were light compared with S group. Conclusions: MMP-2 and MMP-9 expression are significantly increased in emphysema in rats, and propofol can protect lung function in related to inhibit matrix metaloproteinases.%  目的探索异丙酚对肺气肿大鼠血清和气管肺泡灌洗液 MMP-2和 MMP-9的变化及其临床意义。方法Wistar 大鼠30只,体重200-250 g,雌雄不拘。分为三组:吸烟加肺炎克雷伯杆菌感染组(S 组)、异丙酚处理组(P 组)和对照组(C 组)。每组10只。S 组和 P 组采用经鼻吸入肺炎克雷伯杆菌感染的方法染菌,每周1-2次,每次每只动物0.1ml,共10周;两组香烟吸入每次使用12支,分4回燃烧,烟雾通过导管进入约300L 的烟雾吸入箱内,每次2h,每周5次,共16周。C 组动物不吸烟,以培养液代替菌液经鼻吸入。结果光镜下 C 组肺组织结构正常,S 组肺组织呈现结构毁损严重,肺泡塌陷,肺间质水肿,出血,炎症细胞浸润,呈

  9. 基质金属蛋白酶-2、9在根尖周炎中的表达%Expression and Significance of Matrix Metalloproteinase -2 9 in Periodontitis.

    Institute of Scientific and Technical Information of China (English)

    李汉玲; 胡晓春; 隋晓光

    2011-01-01

    Objective: To investigate the role of matrix metalloproteinase-2, 9 (MMP-2, 9) in pathogenesis of periodontitis. Methods: The expressions of MMP-2 9 were detected by immunohistochemical method and the activity of MMP-2 9 were measured by SDS- Page- Zymograph in 18 cases of periapical granuloma, 15 cases of periapical cyst and 10 cases of normal periapical tissue. Results: It was revealed that MMP-2, 9 were positively expressed in plasma cell,macrophage, fibroblast and neutrophilic granulocyte. The SDS-Page-Zymograph analysis indicated that the level of pro-MMP-2 and active MMP-2 were significantly higher in periapical granulomas and periapical cysts than those in normal tissues (P<0.01). The pro-MMP-9 and active MMP-9 were highly detectable in inflamed periapical tissue. The relative expression of MMP- 2, 9 between the periapical granuloma group and the periapical cysts group has no significant difference. Conclusion: MMP-2, 9 may participate in the process of the periodontitis, and play significant roles in the destruction of bone matrix.%目的:探讨基质金属蛋白酶-2、9(MMP-2、9)在根尖周炎发病机制中的作用.方法:采用免疫组化和明胶酶谱法,检测18例根尖肉芽肿、15例根尖囊肿及10例正常根尖组织基质金属蛋白酶-2、9的蛋白表达及酶活性.结果:MMP-2、9在炎症根尖周组织中均有阳性表达,定位于浆细胞、巨噬细胞、成纤维细胞和中性粒细胞.明胶酶谱分析,炎症组MMP-2酶原及活性蛋白表达均高于正常组(P<0.01).炎症组MMP-9酶原及活性的蛋白表达强阳性.根尖肉芽肿组与根尖囊肿组MMP-2、9的蛋白表达及活性比较,差异无统计学意义.结论:MMP-2、9可能参与根尖周炎的发病过程,并在骨破坏中发挥作用.

  10. EXPRESSION OF MATRIX METALLOPROTEINASE-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN HUMAN GLIOMA AND THEIR RELATION TO THE INVASION OF THE TUMOR

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To study the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in different grade human glioma. To investigate their relation to the pathological grade and invasion of the tumor. Methods The expression of MMP-2 and VEGF were determined by immunohistochemical technique in 48 cases of human glioma and 10 specimens of normal brain tissue. Results The expression levels of MMP-2 and VEGF in human glioma were positively related to tumor grades (P<0.01), and their expressions in the glioma of grade Ⅲ and Ⅳ were significantly different from those in the glioma of grade Ⅰ-Ⅱand normal brain tissue (P<0.01). The expression of MMP-2 was positively correlated to that of VEGF (P<0.01). Conclusion MMP-2 and VEGF were highly expression in human glioma and were positively related to the tumor grades. The synergic interaction of MMP-2 and VEGF promoted the angiogenesis and invasion of human glioma.

  11. Gene expression in distinct regions of rat tendons in response to jump training combined with anabolic androgenic steroid administration

    DEFF Research Database (Denmark)

    Marqueti, Rita Cássia; Marqueti, Rita de Cássia; Heinemeier, Katja Maria;

    2012-01-01

    RNA levels of COL1A1, COL3A1, TIMP-1, TIMP-2, MMP-2, IGF-IEa, GAPDH, CTGF and TGF-ß-1 were evaluated by quantitative PCR. Our main results indicated that mRNA levels alter in different regions in each tendon of sedentary animals. The training did not alter the expression of COL1A1, COL3A, IGF-IEa and MMP-2...

  12. Losartan inhibited expression of matrix metalloproteinases in rat atherosclerotic lesions and angiotensin Ⅱ-stimulated macrophages

    Institute of Scientific and Technical Information of China (English)

    ChunLIANG; Zong-guiWU; JianDING; Jian-feiJIANG; Gao-zhongHUANG; Rong-zengDU; Jun-boGE

    2004-01-01

    AIM: To explore whether the angiotensin Ⅱ (Ang Ⅱ) receptor 1 (ATI) antagonist, losartan could reduce activity and expression of matrix metalloproteinases (MMPs) in rat atherosclerotic plaques. METHODS: Male Wistar-Kyoto rats were ip