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Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model

College of Veterinary Medicine, Kyungpook National University, 80 Daehakro, Buk-gu, Daegu 702-701, Korea
Stem Cell Therapeutic Research Institute, Kyungpook National University, 80 Daehakro, Buk-gu, Daegu 702-701, Korea
Korea Research Institute of Bioscience and Biotechnology, Daejon 305-333, Korea
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2014, 15(3), 4126-4141;
Received: 30 December 2013 / Revised: 8 February 2014 / Accepted: 26 February 2014 / Published: 7 March 2014
(This article belongs to the Section Biochemistry)
PDF [4481 KB, uploaded 19 June 2014]


Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection. View Full-Text
Keywords: hepatitis C virus; alcohol; HCV core protein; TG-99 hepatitis C virus; alcohol; HCV core protein; TG-99
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Noh, D.-H.; Lee, E.-J.; Kim, A.-Y.; Lee, E.-M.; Min, C.-W.; Kang, K.-K.; Lee, M.-M.; Kim, S.-H.; Sung, S.-E.; Hwang, M.; Yu, D.-Y.; Jeong, K.-S. Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model. Int. J. Mol. Sci. 2014, 15, 4126-4141.

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