Liu LX, Huang S, Zhang QQ, Liu Y, Zhang DM, Guo XH, Han DW. Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro. World J Gastroenterol 2009; 15(26): 3246-3253 [PMID: 19598300 DOI: 10.3748/wjg.15.3246]
Corresponding Author of This Article
Li-Xin Liu, Institute of Liver Disease of Shanxi Medical University, Mailbox 206, 56 Xinjian South Road, Taiyuan 030001, Shanxi Province, China. lixinl6@yahoo.com
Article-Type of This Article
Original Articles
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jul 14, 2009; 15(26): 3246-3253 Published online Jul 14, 2009. doi: 10.3748/wjg.15.3246
Insulin-like growth factor binding protein-7 induces activation and transdifferentiation of hepatic stellate cells in vitro
Li-Xin Liu, Shuai Huang, Qian-Qian Zhang, Yi Liu, Dong-Mei Zhang, Xiao-Hong Guo, De-Wu Han
Li-Xin Liu, Qian-Qian Zhang, 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
Shuai Huang, Experimental Center of Science and Research of The First Teaching Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Yi Liu, De-Wu Han, Institute of Liver Disease of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Dong-Mei Zhang, The First Teaching Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Xiao-Hong Guo, 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
Author contributions: Liu LX and Huang S contributed equally to this work; Liu LX designed this study; Huang S, Zhang QQ, Liu Y, Zhang DM, Guo XH performed the experiments; Han DW review the paper.
Correspondence to: Li-Xin Liu, Institute of Liver Disease of Shanxi Medical University, Mailbox 206, 56 Xinjian South Road, Taiyuan 030001, Shanxi Province, China. lixinl6@yahoo.com
Telephone: +86-351-8263169
Fax: +86-351-8263169
Received: February 24, 2009 Revised: May 23, 2009 Accepted: May 30, 2009 Published online: July 14, 2009
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.
