【摘要】 本研究采用人胎儿肺来源的成纤维细胞株MRC 5 ,作为体外研究肝细胞生长因子 (HGF)抗组织纤维化的模型。成纤维细胞MRC 5被转化生长因子 β1(TGF β1)转化为肌成纤维细胞后 ,应用外源人重组HGF修饰细胞 ,检测细胞中分子表达水平的变化。研究发现 ,TGF β1在诱导成纤维细胞株MRC 5转化为肌成纤维细胞的同时 ,上调HGF受体 c Met在肌成纤维细胞中的表达。而且 ,应用外源人重组HGF修饰细胞后 ,内源性TGF β1的表达水平被降低 ,内源性HGF的表达水平上调 ,基质金属蛋白酶I (MMP I)mRNA表达增加 ,从而加速了细胞外基质主要成分—胶原蛋白I [Col (I) ]的水解。结果显示在组织纤维化过程中 ,HGF通过其受体c Met直接作用于肌成纤维细胞 ,抑制细胞内TGF β1的表达 ,在一定程度上抑制组织纤维化的发生和发展。研究中我们还发现 ,肝素结合表皮生长因子样生长因子 (HB EGF)上调肌成纤维细胞中HGF的表达 ,是其抑制肌成纤维细胞形成、抑制组织纤维化的可能机制之一更多还原

【Abstract】 In the present study, human embryonic lung fibroblasts MRC 5 were used as a model to identify the antifibrotic mechanism of HGF in vitro. We found that TGF β1 up regulated c Met expression in myofibroblastic MRC 5. And after the cells were transformed into myofibroblasts by TGF β1 and then cultured in the presence of HGF, endogenous TGF β1 concentration declined while HGF secretion enhanced. Consistent with these events, HGF stimulated matrix mentalloproteinase I(MMP 1) mRNA expression and enhanced subsequent proteolysis of type I collagen (Col (I)). These results indicated that HGF administration, at least in some extent, directly elicit anti fibrotic effects on myofibroblasts in organs undergone tissue fibrosis. Moreover, we also found that one of the mechanisms for heparin binding epithelial growth factor like growth factor (HB EGF) reducing myofibroblast formation may function by up regulating HGF expression.更多还原