Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro |
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Authors: | Li-Xin Liu Shuai Huang Qian-Qian Zhang Yi Liu Dong-Mei Zhang Xiao-Hong Guo De-Wu Han |
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Institution: | 1. Experimental Center of Science and Research of The First Teaching Hospital of Shanxi Medical University, Institute of Liver Disease of Shanxi Medical University and Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Taiyuan 030001,Shanxi Province, China 2. Experimental Center of Science and Research of The First Teaching Hospital of Shanxi Medical University,Taiyuan 030001, Shanxi Province, China 3. Institute of Liver Disease of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China 4. The First Teaching Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China 5. Experimental Center of Science and Research of The First Teaching Hospital of Shanxi Medical University, and Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Taiyuan 030001, Shanxi Province,China |
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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,col lagen Ⅰ and α-SMA al so 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. |
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Keywords: | Insulin-like growth factor-binding protein- Smooth muscle actin Fibronectins Hepatic stellate cells |
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