Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro  

作　　者：Li-Xin Liu Shuai Huang Qian-Qian Zhang Yi Liu Dong-Mei Zhang Xiao-Hong Guo De-Wu Han 

机构地区：[1]Experimental Center of Science and Research of The First Teaching Hospital of Shanxi Medical University,Taiyuan 030001, Shanxi Province, China [2]Institute of Liver Disease of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China [3]The First Teaching Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China [4]Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Taiyuan 030001, Shanxi Province,China

出　　处：《World Journal of Gastroenterology》2009年第26期3246-3253,共8页世界胃肠病学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China No.30740031,No.30871146;the New Century Excellent Talent of the Ministry of Education of China,No.NCET-06-0264

摘　　要：AIM:To investigate the role of insulin-like growth factor binding protein-7 (IGFBP-7) in the activation and transdifferentiation of hepatic stellate cells (HSC) in vitro.METHODS:Rat HSC-T6 cells were cultured in separate dishes and treated with various concentration of transforming growth factor (TGF)-β1,IGFBP-7 or antiIGFBP-7 antibody for 24 h.The supernatant or a cytoplasm suspension was obtained from cultured HSC,followed by transfer of cells to form cell-coated dishes.Immunocytochemistry and Western blotting were used to analyze the expression of IGFBP-7 induced by TGF-β1 and the level of fibronectin,collagen and α-smooth muscle actin (SMA).The pro-apoptotic effect of antiIGFBP-7 antibody was determined by flow cytometry.RESULTS:Immunocytochemistry and Western blotting revealed that the expression of IGFBP-7 in TGF-β1 treated HSC was significantly up-regulated compared to that in the control group.In addition,fibronectin,collagen and α-SMA also showed enhanced expression in accordance with the transdifferentiation process in a dose-dependent manner to some extent.Moreover,flow cytometry suggested that anti-IGFBP-7 antibody induced apoptosis of activated HSC,which is responsible for the development of liver fibrosis,and may represent a novel pathway and target for therapeutic intervention.CONCLUSION:IGFBP-7 showed increased expression in activated HSC and played an important role in the activation and transdifferentiation process of HSC.AntiIGFBP-7 antibody may ameliorate liver fibrogenesis.AIM： To investigate the role of insulin-like growth factor binding protein-7 （IGFBP-7） in the activation and transdifferentiation of hepatic stellate cells （HSC） in vitro. METHODS： Rat HSC-T6 cells were cultured in separate dishes and treated with various concentration of transforming growth factor （TGF）-β1, IGFBP-7 or anti- IGFBP-7 antibody for 24 h. The supernatant or a cytoplasm suspension was obtained from cultured HSC, followed by transfer of cells to form cell-coated dishes. Immunocytochemistry and Western blotting were used to analyze the expression of IGFBP-7 induced by TGF-β1 and the level of fibronectin, collagen Ⅰ and α-smooth muscle actin （SMA）. The pro-apoptotic effect of anti- IGFBP-7 antibody was determined by flow cytometry. RESULTS： Immunocytochemistry and Western blotting revealed that the expression of IGFBP-7 in TGF-β1 treated HSC was significantly up-regulated compared to that in the control group. In addition, fibronectin, collagen Ⅰ and α-SMA also showed enhanced expression in accordance with the transdifferentiation process in a dose-dependent manner to some extent. Moreover, flow cytometry suggested that anti-IGFBP-7 antibody induced apoptosis of activated HSC, which is responsible for the development of liver fibrosis, and may represent a novel pathway and target for therapeutic intervention. CONCLUSION： IGFBP-7 showed increased expression in activated HSC and played an important role in the activation and transdifferentiation process of HSC. Anti- IGFBP-7 antibody may ameliorate liver fibrogenesis.

关 键 词：Insulin-like growth factor-binding protein-7 Smooth muscle actin FIBRONECTINS Collagen type Ⅰ Hepatic stellate cells 

分 类 号：Q55[生物学—生物化学] S823.5[农业科学—畜牧学]