结缔组织生长因子通过ERK1/2和PI3K信号通路促进大鼠肝星状细胞迁移和基质金属蛋白酶2表达  

CTGF promoting migration and MMP-2 expression via ERK1/2 and PI3K pathway in rat hepatic stellate cells

作　　者：甄茂川[1] 刘平果[1] 赵一麟[1] 吴绍峰[1] 俞可克[1] 尹震宇[1] 

机构地区：[1]厦门大学附属中山医院肝胆外科,361004

出　　处：《中华普通外科学文献（电子版）》2014年第5期13-17,共5页Chinese Archives of General Surgery(Electronic Edition)

基　　金：国家自然基金资助项目(30872484);福建省医学创新基金资助项目(2009-CXB-56)

摘　　要：目的研究结缔组织生长因子(CTGF)对大鼠肝星状细胞(HSC)迁移及基质金属蛋白酶2(MMP-2)表达及活化的影响。方法分别应用RT-PCR和Western blotting法检测MMP-2表达,明胶酶谱法检测MMP-2的活性;运用Western blotting法检测ERK1/2和Akt的磷酸化水平。运用Transwell小室检测肝星状细胞迁移能力。结果 CTGF呈剂量依赖性促进大鼠HSC中MMP-2 m RNA和蛋白表达;同时CTGF能够促进HSC迁移,MMP-2特异性抑制剂能够抑制CTGF的促迁移作用。ERK1/2和PI3K抑制剂能够显著抑制CTGF诱导的MMP-2表达以及CTGF促进HSC的迁移作用。结论 MMP-2表达和活性的增强在CTGF促进HSC迁移过程中发挥着重要作用,ERK1/2和PI3K信号通路在CTGF促进MMP-2表达发挥关键作用。Objective To identify the role of connective tissue growth factor （CTGF） in hepatic stellate cell （HSC） migration and its effects on gelatinase matrix metalloproteinase-2 （MMP-2） expression and activation. Methods The expression of MMP-2 was assessed by RT-PCR and Western blotting analyses. MMP-2 activity was evaluated by zymography. ERK1/2 and Akt phosphorylation were determined by Western blotting analysis. HSC migration was performed using Transwell cell culture chambers. Results The expression of MMP-2 mRNA and protein in HSCs were substantially increased by CTGF treatment in a dose-dependent manner. In addition, CTGF could promote HSC migration, and the addition of MMP-2-specific inhibitor impaired this phenomenon. To study the intracellular signaling pathways involved in CTGF-induced MMP-2 expression, we evaluated the effects of different kinase inhibitors. The inhibitors of extracellular signal-regulated kinase 1/2 （ERK1/2） and phosphatidyl inositol 3-kinase （PI3K） abrogated CTGF-elicited MMP-2 upregulation and significantly reduced CTGF-induced invasiveness of HSC. Conclusion MMP-2 plays an important role in the invasive effects of CTGF on HSC. ERK1/2 and PI3K are the main signals involved in CTFG-mediated MMP-2 expression.

关 键 词：基质金属蛋白酶 肝星状细胞 迁移 结缔组织生长因子 

分 类 号：R575.2[医药卫生—消化系统]