Korean J Gastroenterol.
2003 Nov;42(5):400-408.
The Role of Hepatitis C Virus Core Protein on Liver Fibrogenesis: A Study Using an In Vitro Co-culture System
- Affiliations
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- 1Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea. yoonsk@cmc.cuk.ac.kr
- 2WHO Collaborating Center of Viral Hepatitis, Seoul, Korea.
- 3Department of Life Science, Pohang University of Science and Technology, Pohang, Korea.
Abstract
- 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.
MeSH Terms
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Actins/metabolism
Animals
Cell Line, Tumor
Coculture Techniques
Connective Tissue Growth Factor
Fibrosis
Hepatitis C Antigens/*physiology
Humans
Immediate-Early Proteins/metabolism
Immunoblotting
Immunohistochemistry
Intercellular Signaling Peptides and Proteins/metabolism
Liver/metabolism/*pathology
Protein-Serine-Threonine Kinases
Rats
Rats, Sprague-Dawley
Receptors, Transforming Growth Factor beta/metabolism
Transforming Growth Factor beta/metabolism
Transforming Growth Factor beta1
Viral Core Proteins/*physiology
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