HCV core protein promotes liver fibrogenesis via up-regulation of CTGF with TGF-beta1.
- Author:
Ju Yeop SHIN
1
;
Wonhee HUR
;
Jin Sang WANG
;
Jeong Won JANG
;
Chang Wook KIM
;
Si Hyun BAE
;
Sung Key JANG
;
Se Hwan YANG
;
Young Chul SUNG
;
Oh Joo KWON
;
Seung Kew YOON
Author Information
1. WHO Collaborating Center of Viral Hepatitis, Korea. yoonsk@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
connective tissue growth factor;
fibrogenesis;
hepatitis C virus;
liver cirrhosis;
stellate cell
- MeSH:
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
- From:Experimental & Molecular Medicine
2005;37(2):138-145
- CountryRepublic of Korea
- Language:English
-
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.
