Objective To investigate the regulatory effect of multifactor on the matrix metalloproteinases-9 （MMP-9） and the tissue inhibitor of metalloproteinase-1 （TIMP-1） in endometrial stromal cells. Methods The endometri...Objective To investigate the regulatory effect of multifactor on the matrix metalloproteinases-9 （MMP-9） and the tissue inhibitor of metalloproteinase-1 （TIMP-1） in endometrial stromal cells. Methods The endometrial stromal cells separated from the proliferative endometrial tissues were incubated with medium alone, 17-β estradiol （E2,10^-8 mol/L）, medroxyprogesterone acetate （MPA, 10^-6 mol/L）, E2（10^-8 mol/L）＋MPA （10^-6 mol/L）, E2 （10^-8 mol/L）＋MPA （10^-6 mol/L）＋RU486 （10^-5 mol/L） or HB-EGF （10 ng/ml） for 48 h respectively. The expressions of MMP-9 and TIMP-1 were detected by in situ hybridization, immunocytochemistry, reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blotting. Results Compared with control group [mRNA, 0. 729 ± 0. 090 （MMP-9） and 1.056± 0.154 （TIMP-1）; protein, 0.545 ±0.086 （MMP-9） and 0.745 ±0.154 （TIMP-1）], expressions of MMP-9 and TIMP-1 in E2 alone, progestin alone or E2 combined with progestin group were respectively：mRNA, 0.413 ± 0.069, 0.402 ± 0.073 and 0.407 ± 0.039; 0.487 ± 0.093, 0.503 ± 0.093 and 0.468 ± 0.075：protein, 0.294 ± 0.076, 0.331 ±0.064 and 0.265 ±0.049; 0.425 ±0.085, 0.397 ±0.065 and 0.435 ± 0.099. RU486 weakened the expression level of down-regulation, while HB-EGF elevated the level of MMP-9 and TIMP-1 after 48 h treatment （mRNA, 0.955 ± 0.068 and 1.396 ± 0.238; protein, 0. 780 ± 0.109 and 0.985 ± 0.165）. Conclusions 1） Both E2 and progestin can down-regulate the expressions of MMP-9 and TIMP-1 in endometrial stromal cells, but RU486 can inhibit the effect. 2） HB-EGF can elevate the level of MMP-9 and TIMP-1. 3） E2, progestin and HB-EGF have effect on the ratio of MM-P/TIMP-1.展开更多
Objective To investigate the role of matrix metalloproteinase-1 （MMP-1）/protease- activated receptor-1 （PAR-l） signaling in the cervical cancer invasion. Methods RT-PCR was used to test the mRNA level of MMP-1 in ...Objective To investigate the role of matrix metalloproteinase-1 （MMP-1）/protease- activated receptor-1 （PAR-l） signaling in the cervical cancer invasion. Methods RT-PCR was used to test the mRNA level of MMP-1 in 59 cases of cervical squamous cell cancer. Cell invasion was evaluated by Transwell assay to explore the effect of adding human recombinant MMP-1 （rhMMP-1） and PARI-siRNA on cervical cancer invasion. Results In cervical cancer tissues, more MMP-1 expression was observed than that in the normal cervical tissues, and its expression correlated with cancer status. Human recombinant MMP-1 （rhMMP-1） could promote Hela cell invasion, and its number of invasive cell correlated with the concentration of rhMMP-1. Disrupting the expression of PAR-1 reduced the MMP-1 promoting-effect on Hela cell invasion, but had no effect on non-MMP-1 invasive action. Conclusion The MMP-1/PAR-1 signaling pathway is involved in cervical cancer invasion. Therefore, blocking PAR-1 may represent a new therapeutic option for metastatic cervical cancer.展开更多
目的研究活动期类风湿关节炎(rheum atoid arthritis,RA)患者血清基质金属蛋白酶-3(m atrix m etalloproteinase3,M M P-3)、金属蛋白酶组织抑制剂-1(tissue inhibitors ofm etalloproteinase1,TIM P-1)的水平及其相关影响因素,探讨M M ...目的研究活动期类风湿关节炎(rheum atoid arthritis,RA)患者血清基质金属蛋白酶-3(m atrix m etalloproteinase3,M M P-3)、金属蛋白酶组织抑制剂-1(tissue inhibitors ofm etalloproteinase1,TIM P-1)的水平及其相关影响因素,探讨M M P-3及TIM P-1在R A的作用机制。方法选择41例初诊活动期RA患者和30名正常健康志愿者,以酶联免疫吸附试验(ELISA)分别检测血清M M P-3及TIM P-1水平,计算M M P-3/TIM P-1,同时测定关节功能、X线、关节肿胀数(SJC)、血沉(ESR)、类风湿因子(R F)、C反应蛋白(CR P)等相关实验室指标。结果活动期R A患者血清M M P-3、TIM P-1明显增高(P<0.01),且以M M P-3增高更为显著,M M P-3/TIM P-1较正常组亦增高(P<0.05)。不同关节功能分级时,上述指标差异无统计学意义(P>0.05),而不同X线分期时,各指标差异有统计学意义(P<0.01或P<0.05)。M M P-3、M M P-3/TIM P-1与SJC(P<0.01)、CRP(P<0.01)、ESR(P<0.05)呈正相关,二者与年龄、病程、晨僵时间、RF无明显相关性(P>0.05)。结论M M P-3、TIM P-1在RA血清中高水平存在,二者比例失衡导致RA发生。M M P-3、M M P-3/TIM P-1的高低可作为反映病情活动及预后的指标,阻断M M P-3高水平有可能成为治疗RA的新途径之一。展开更多
文摘Objective To investigate the regulatory effect of multifactor on the matrix metalloproteinases-9 （MMP-9） and the tissue inhibitor of metalloproteinase-1 （TIMP-1） in endometrial stromal cells. Methods The endometrial stromal cells separated from the proliferative endometrial tissues were incubated with medium alone, 17-β estradiol （E2,10^-8 mol/L）, medroxyprogesterone acetate （MPA, 10^-6 mol/L）, E2（10^-8 mol/L）＋MPA （10^-6 mol/L）, E2 （10^-8 mol/L）＋MPA （10^-6 mol/L）＋RU486 （10^-5 mol/L） or HB-EGF （10 ng/ml） for 48 h respectively. The expressions of MMP-9 and TIMP-1 were detected by in situ hybridization, immunocytochemistry, reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blotting. Results Compared with control group [mRNA, 0. 729 ± 0. 090 （MMP-9） and 1.056± 0.154 （TIMP-1）; protein, 0.545 ±0.086 （MMP-9） and 0.745 ±0.154 （TIMP-1）], expressions of MMP-9 and TIMP-1 in E2 alone, progestin alone or E2 combined with progestin group were respectively：mRNA, 0.413 ± 0.069, 0.402 ± 0.073 and 0.407 ± 0.039; 0.487 ± 0.093, 0.503 ± 0.093 and 0.468 ± 0.075：protein, 0.294 ± 0.076, 0.331 ±0.064 and 0.265 ±0.049; 0.425 ±0.085, 0.397 ±0.065 and 0.435 ± 0.099. RU486 weakened the expression level of down-regulation, while HB-EGF elevated the level of MMP-9 and TIMP-1 after 48 h treatment （mRNA, 0.955 ± 0.068 and 1.396 ± 0.238; protein, 0. 780 ± 0.109 and 0.985 ± 0.165）. Conclusions 1） Both E2 and progestin can down-regulate the expressions of MMP-9 and TIMP-1 in endometrial stromal cells, but RU486 can inhibit the effect. 2） HB-EGF can elevate the level of MMP-9 and TIMP-1. 3） E2, progestin and HB-EGF have effect on the ratio of MM-P/TIMP-1.
基金supported by the project of Shanghai Municipal Health Bureau(2011160)
文摘Objective To investigate the role of matrix metalloproteinase-1 （MMP-1）/protease- activated receptor-1 （PAR-l） signaling in the cervical cancer invasion. Methods RT-PCR was used to test the mRNA level of MMP-1 in 59 cases of cervical squamous cell cancer. Cell invasion was evaluated by Transwell assay to explore the effect of adding human recombinant MMP-1 （rhMMP-1） and PARI-siRNA on cervical cancer invasion. Results In cervical cancer tissues, more MMP-1 expression was observed than that in the normal cervical tissues, and its expression correlated with cancer status. Human recombinant MMP-1 （rhMMP-1） could promote Hela cell invasion, and its number of invasive cell correlated with the concentration of rhMMP-1. Disrupting the expression of PAR-1 reduced the MMP-1 promoting-effect on Hela cell invasion, but had no effect on non-MMP-1 invasive action. Conclusion The MMP-1/PAR-1 signaling pathway is involved in cervical cancer invasion. Therefore, blocking PAR-1 may represent a new therapeutic option for metastatic cervical cancer.
文摘目的研究活动期类风湿关节炎(rheum atoid arthritis,RA)患者血清基质金属蛋白酶-3(m atrix m etalloproteinase3,M M P-3)、金属蛋白酶组织抑制剂-1(tissue inhibitors ofm etalloproteinase1,TIM P-1)的水平及其相关影响因素,探讨M M P-3及TIM P-1在R A的作用机制。方法选择41例初诊活动期RA患者和30名正常健康志愿者,以酶联免疫吸附试验(ELISA)分别检测血清M M P-3及TIM P-1水平,计算M M P-3/TIM P-1,同时测定关节功能、X线、关节肿胀数(SJC)、血沉(ESR)、类风湿因子(R F)、C反应蛋白(CR P)等相关实验室指标。结果活动期R A患者血清M M P-3、TIM P-1明显增高(P<0.01),且以M M P-3增高更为显著,M M P-3/TIM P-1较正常组亦增高(P<0.05)。不同关节功能分级时,上述指标差异无统计学意义(P>0.05),而不同X线分期时,各指标差异有统计学意义(P<0.01或P<0.05)。M M P-3、M M P-3/TIM P-1与SJC(P<0.01)、CRP(P<0.01)、ESR(P<0.05)呈正相关,二者与年龄、病程、晨僵时间、RF无明显相关性(P>0.05)。结论M M P-3、TIM P-1在RA血清中高水平存在,二者比例失衡导致RA发生。M M P-3、M M P-3/TIM P-1的高低可作为反映病情活动及预后的指标,阻断M M P-3高水平有可能成为治疗RA的新途径之一。
