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

International Journal of Molecular Sciences

Dong-Hyung Noh²  Eun-Joo Lee²  Ah-Young Kim²  Eun-Mi Lee²  Chang-Woo Min²  Kyung-Ku Kang²  Myeong-Mi Lee²  Sang-Hyeob Kim²  Soo-Eun Sung²  Meeyul Hwang²  Dae-Yeul Yu¹ 

[1] Korea Research Institute of Bioscience and Biotechnology, Daejon 305-333, Korea; E-Mail:;College of Veterinary Medicine, Kyungpook National University, 80 Daehakro, Buk-gu, Daegu 702-701, Korea; E-Mails:

关键词: hepatitis C virus;    alcohol;    HCV core protein;    TG-99;   

DOI  :  10.3390/ijms15034126

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland