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

Abstract

Objective The aim of this study was to investigate the role of insulin‐like growth factor binding protein‐related protein 1 ( IGFBP ‐r P 1) in the development of hepatic fibrogenesis in experimental disease models and human liver samples. Methods Cellular distribution patterns of IGFBP ‐r P 1 were assessed by immunohistochemistry in fibrotic and cirrhotic human liver specimens. Gene silencing of IGFBP ‐r P 1 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 P 1 on the production of extracellular matrix ( ECM ) components by W estern 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 P 1 (r IGFBP ‐r P 1). Results Expression of IGFBP ‐r P 1 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 P 1 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 P 1‐treated mice. Conclusions IGFBP ‐r P 1 contributes to the development of liver fibrosis and may be a novel molecule involved in the progression of hepatic fibrogenesis.