Exp Mol Med.  2005 Apr;37(2):138-145.

HCV core protein promotes liver fibrogenesis via up-regulation of CTGF with TGF-beta1

• Shin JY
• Hur W
• Wang JS
• Jang JW
• Kim CW
• Bae SH
• Jang SK
• Yang SH
• Sung YC
• Kwon OJ
• Yoon SK

Abstract

Liver cirrhosis is one of the major complications of hepatitis C virus (HCV) infection, but the mechanisms underlying HCV-related fibrogenesis are still not clear. Although the roles of HCV core protein remain poorly understood, it is supposed to play an important role in the regulation of cellular growth and hepatocarcinogenesis. The aim of this study was to examine the role of HCV core protein on the hepatic fibrogenesis. We established an in vitro co-culture system with primary hepatic stellate cell (HSC) isolated from rats, and a stable HepG2-HCV core cell line which had been transfected with HCV core gene. The expressions of fibrosis-related molecules transforming growth factor beta1 (TGF-beta1), transforming growth factor b receptor II (TGF beta RII), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were analyzed via histological or molecular methods. In addition, the expression levels of matrix metaloprotinase-2 (MMP-2) and collagen type I (Col I) from the co-cultured media were measured by zymogram and ELISA, respectively. The expressions of alpha-SMA, TGF-beta1, Col I, TGF beta RII and MMP-2 were significantly increased in the co-culture of stable HepG2-HCV core with HSC. Moreover, the significant increases of CTGF and TGF-beta1 in the HCV core-expressing cells were observed by either Northern or Western blot analysis. These results suggest that HCV core protein may contribute to the hepatic fibrogenesis via up-regulation of CTGF and TGF-beta1.

Keyword

connective tissue growth factor; fibrogenesis; hepatitis C virus; liver cirrhosis; stellate cell

MeSH Terms

Actins/metabolism
Animals
Cell Line, Tumor
Cells, Cultured
Coculture Techniques
Collagen Type I/metabolism
Gelatinase A/metabolism
Immediate-Early Proteins/*biosynthesis
Intercellular Signaling Peptides and Proteins/*biosynthesis
Liver/metabolism/*pathology
Liver Cirrhosis/*metabolism
Male
Rats
Rats, Sprague-Dawley
Receptors, Transforming Growth Factor beta/metabolism
Research Support, Non-U.S. Gov't
Transforming Growth Factor beta/*metabolism
Up-Regulation
Viral Core Proteins/genetics/*metabolism