Mechanism of TGF-β1 on the expression of CTGF and type I collagen in hepatic stellate cells.

• Main Authors: Hui Lin Yang, 楊慧霖
• Other Authors: T. L. Hwang
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/74315930419119430793

碩士 === 長庚大學 === 中醫學系天然藥物 === 101 === Liver fibrosis is a significant health issue worldwide and continues to increase in prevalence in Taiwan. The main character of liver fibrosis is excessive production of extracellular matrixes and pro-inflammatory factors. Activated hepatic stellate cells (aHSCs) produce high concentrations of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and type I collagen which are closely related to the pathogenesis of liver fibrosis. However, the effects and action mechanisms of TGF-β1 on CTGF and type I collagen expression remain controversial in HSC. Also, the mechanism of CTGF on collagen expression is still not confirmed. In this study, we demonstrated that TGF-β1 significantly induced the protein and mRNA expression of CTGF and type I collagen in concentration- and time-dependent manners in LX-2 cells, a human HSC cell line. Furthermore, we demonstrated that signaling through TGF-β type I receptor was required for TGF-β1-induced CTGF and type I collagen production. Additional experiments were performed to investigate the role of CTGF in type I collagen production. First, CTGF siRNA abrogated TGF-β1-induced CTGF protein expression, but partially inhibited TGF-β1-induced type I collagen protein expression. Second, recombinant CTGF induced expression of type I collagen in HSCs. Multiple observations made in the study suggested that TGF-β1 induced type I collagen expression through a TGF-β type I receptor-mediated Smad2/3 and Akt signaling pathways. Then, activation of Smad2/3 was responsible for TGF-β1-induced CTGF synthesis. Interestingly, by depleting endogenous CTGF and adding recombinant CTGF show that TGF-β1-induced CTGF production has a positive feedback action on type I collagen expression through Akt signaling pathway. In conclusion, our study can contribute to the pro-fibrotic TGF-β signaling and suggest that this pathway may be beneficial for the treatment of liver fibrosis.