TITLE

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

AUTHOR(S)
Li-Xin Liu; Shuai Huang; Qian-Qian Zhang; Yi Liu; Dong-Mei Zhang; Xiao-Hong Guo; De-Wu Han; Braet, Filip
PUB. DATE
July 2009
SOURCE
World Journal of Gastroenterology;7/14/2009, Vol. 15 Issue 26, p3246
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
43702020

 

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