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J Dig Dis. 2014 Apr;15(4):202-10. doi: 10.1111/1751-2980.12126.

Insulin-like growth factor binding protein-related protein 1 contributes to hepatic fibrogenesis.

Author information

1
Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China; Experimental Center of Science and Research, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China; Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi Province, China.

Abstract

OBJECTIVE:

The aim of this study was to investigate the role of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) in the development of hepatic fibrogenesis in experimental disease models and human liver samples.

METHODS:

Cellular distribution patterns of IGFBP-rP1 were assessed by immunohistochemistry in fibrotic and cirrhotic human liver specimens. Gene silencing of IGFBP-rP1 was performed on cultured hepatic stellate cells (HSCs) by small interfering RNA (siRNA), and the silencing effect was determined by quantitative real-time polymerase chain reaction (PCR) and Western blot. We also determined the effects of siRNA-mediated gene silencing of IGFBP-rP1 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-rP1 (rIGFBP-rP1).

RESULTS:

Expression of IGFBP-rP1 was significantly elevated in fibrotic and cirrhotic human liver specimens, and this increase was positively correlated with the number of collagen fibers observed. siRNA-mediated gene silencing of IGFBP-rP1 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 rIGFBP-rP1-treated mice.

CONCLUSIONS:

IGFBP-rP1 contributes to the development of liver fibrosis and may be a novel molecule involved in the progression of hepatic fibrogenesis.

KEYWORDS:

extracellular matrix; hepatic fibrosis; hepatic stellate cells; insulin-like growth factor binding protein-related protein 1; transforming growth factor β1

PMID:
24373620
DOI:
10.1111/1751-2980.12126
[Indexed for MEDLINE]

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