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KMID : 0614620030420050400
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Korean Journal of Gastroenterology
2003 Volume.42 No. 5 p.400 ~ p.408
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The Role of Hepatitis C Virus Core Protein on Liver Fibrogenesis: A Study Using an In Vitro Co-culture System
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신주엽/Shin JY
윤승규/왕진상/허원희/류종순/배시현/최종영/양진모/양세환/성영철/정규원/Yoon SK/Wang JS/Hur W/Ryu JS/Bae SH/Choi JY/Yang JM/Yang SH/Sung YC/Chung KW/Sun HS
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Abstract
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BACKGROUND/AIMS: The study of liver fibrogenesis by hepatitis C virus (HCV) has been limited due to the lack of an efficiency in vitro culture systems. In the present study, we investigated whether or not HCV core protein is directly related to liver fibrogenesis through stimulation of hepatic stellate cells (HSC).
METHODS: Human and rat HSC were isolated and we established an in vitro co-culture system of a stable HepG2-HCV core cell line which was transfected with HCV core gene and primary HSC. We performed immunocytochemical staining and Western and Northern blot analysis in the stimulated HSC by HCV ocre protein to identify the expression of transforming growth factor beta1 (TGF-beta1), transforming growth factor beta receptor II (TGFbeta R II), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF). The expression of matrix metaloprotinase-2 (MMP-2) and collagen type I (Col I) in the culture media were measured by zymogram and ELISA, respectively.
RESULTS: The expression of TGF-beta1 and CTGF was significantly higher in the stable HepG2-HCV core cell line than in HepG2 cells. Furthermore, the makers related to fibrosis such as alpha-SMA, TGF-beta1, Col I, TGFRII and MMP-2 were highly experssed in the co-culture of stable HepG2-HCV core with HSC.
CONCLUSIONS: HCV core protein may play a direct role in the fibrogenesis of chronic liver disease with HCV infection
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