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시험관내 공동배양법을 이용한 C형 간염 바이러스 Core 단백이 간섬유화 기전에 미치는 영향
신주엽 ( Sin Ju Yeob ),윤승규 ( Yun Seung Gyu ),왕진상 ( Wang Jin Sang ),허원희 ( Heo Won Hui ),류종순 ( Lyu Jong Sun ),배시현 ( Bae Si Hyeon ),최종영 ( Choe Jong Yeong ),양진모 ( Yang Jin Mo ),양세환 ( Yang Se Hwan ),성영철 ( Seo 대한소화기학회 2003 대한소화기학회지 Vol.42 No.5
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 β1 (TGF-β1), transforming growth factor β receptor II (TGFβRII), α-smooth muscle actin (α-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-β1 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 α-SMA, TGF-β1, 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. (Korean J Gastroenterol 2003;42:400-408)