1. Insulin-like growth factor binding protein-related protein 1 contributes to hepatic fibrogenesis.
- Author
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Guo, Xiao Hong, Liu, Li Xin, Zhang, Hai Yan, Zhang, Qian Qian, Li, Yuan, Tian, Xiao Xia, and Qiu, Zhi Hong
- Subjects
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SOMATOMEDIN , *CARRIER proteins , *LIVER diseases , *GENE silencing , *POLYMERASE chain reaction - Abstract
Objective The aim of this study was to investigate the role of insulin-like growth factor binding protein-related protein 1 ( IGFBP-r P1) in the development of hepatic fibrogenesis in experimental disease models and human liver samples. Methods Cellular distribution patterns of IGFBP-r P1 were assessed by immunohistochemistry in fibrotic and cirrhotic human liver specimens. Gene silencing of IGFBP-r P1 was performed on cultured hepatic stellate cells ( HSCs) by small interfering RNA (si RNA), and the silencing effect was determined by quantitative real-time polymerase chain reaction ( PCR) and Western blot. We also determined the effects of si RNA-mediated gene silencing of IGFBP-r P1 on the production of extracellular matrix ( ECM) components by Western blot. The expression of ECM components and transforming growth factor ( TGF)-β1 was studied by immunohistochemistry and Western blot in C57BL/6 wild-type mice treated with recombinant IGFBP-r P1 (r IGFBP-r P1). Results Expression of IGFBP-r P1 was significantly elevated in fibrotic and cirrhotic human liver specimens, and this increase was positively correlated with the number of collagen fibers observed. si RNA-mediated gene silencing of IGFBP-r P1 resulted in significantly decreased levels of collagen I and fibronectin in HSCs. Moreover, IGFBP-rP1 overexpression significantly increased the production of collagen, fibronectin and TGF-β1 in r IGFBP-r P1-treated mice. Conclusions IGFBP-r P1 contributes to the development of liver fibrosis and may be a novel molecule involved in the progression of hepatic fibrogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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