HCV core protein promotes liver fibrogenesis via up-regulation of CTGF with TGF-beta1.
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 beta receptor II (TGFbetaRII), 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, TGFbetaRII 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.
Shin
Ju Yeop
JY
WHO Collaborating Center of Viral Hepatitis, The Catholic University of Korea, Seoul, Korea.
Hur
Wonhee
W
Wang
Jin Sang
JS
Jang
Jeong Won
JW
Kim
Chang Wook
CW
Bae
Si Hyun
SH
Jang
Sung Key
SK
Yang
Se-Hwan
SH
Sung
Young Chul
YC
Kwon
Oh-Joo
OJ
Yoon
Seung Kew
SK
D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D024042:Collagen Type I; D055513:Connective Tissue Growth Factor; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020778:Matrix Metalloproteinase 2; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014758:Viral Core Proteins; C526316:CCN2 protein, rat; C508962:Tgfb1 protein, rat; C069130:nucleocapsid protein, Hepatitis C virus; C498862:Acta2 protein, rat