期刊
JOURNAL OF PATHOLOGY
卷 219, 期 2, 页码 253-262出版社
WILEY
DOI: 10.1002/path.2592
关键词
hepatitis C virus; liver pathogenesis; NS5A protein; steatosis; transgenic mice
资金
- 21st Century Frontier Programme in the Functional Human Genome Project of Korea [HGM0200833]
- KRIBB Research Initiative Programme Grant, by the Research Programme for New Drug Target Discovery [M10601000044-06N0100-04410]
- Biotechnology Development [2008-04100]
- Ministry of Education, Science and Technology [120A-2007-000-20051-0]
- BioGreen 21 programme, Rural Development Administration, Korea [20070401034015]
- Rural Development Administration (RDA), Republic of Korea [20070401034015] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). However, the mechanism of HCV pathogenesis is not well understood. Our previous in vitro studies suggested that non-structural 5A (NS5A) protein may play an important role in liver pathogenesis. To elucidate the mechanism of HCV-induced liver pathogenesis, we investigated the histopathological changes of liver in transgenic mice harbouring the NS5A gene. We generated transgenic mice harbouring HCV NS5A gene under the control of hepatitis B virus (HBV) enhancer. Pathological changes were analysed by immunohistochemical staining and western blot analysis. Lipid composition and reactive oxygen species (ROS) production in NS5A transgenic mice were analysed. HCV NS5A transgenic mice developed extraordinary steatosis over 6 months old and induced HCC in some mice. NS5A was co-localized with apolipoprotein A-1 in fatty hepatocytes. In addition, the extraordinarily high levels of ROS, NF-kappa B and STAT3 were detected in hepatocytes of NS5A transgenic mice. These data suggest that NS5A, independent of other HCV viral proteins, may play an important role in the development of hepatic pathologies, including steatosis and hepatoceullular carcinoma in transgenic mice. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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