Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Noh, Dong-Hyung, Lee, Eun-Joo, Kim, Ah-Young, Lee, Eun-Mi, Min, Chang-Woo, Kang, Kyung-Ku, Lee, Myeong-Mi, Kim, Sang-Hyeob, Sung, Soo-Eun, Hwang, Meeyul, Yu, Dae-Yeul, Jeong, Kyu-Shik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975388/
https://www.ncbi.nlm.nih.gov/pubmed/24608925
http://dx.doi.org/10.3390/ijms15034126
_version_ 1782310142410227712
author Noh, Dong-Hyung
Lee, Eun-Joo
Kim, Ah-Young
Lee, Eun-Mi
Min, Chang-Woo
Kang, Kyung-Ku
Lee, Myeong-Mi
Kim, Sang-Hyeob
Sung, Soo-Eun
Hwang, Meeyul
Yu, Dae-Yeul
Jeong, Kyu-Shik
author_facet Noh, Dong-Hyung
Lee, Eun-Joo
Kim, Ah-Young
Lee, Eun-Mi
Min, Chang-Woo
Kang, Kyung-Ku
Lee, Myeong-Mi
Kim, Sang-Hyeob
Sung, Soo-Eun
Hwang, Meeyul
Yu, Dae-Yeul
Jeong, Kyu-Shik
author_sort Noh, Dong-Hyung
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3975388
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Molecular Diversity Preservation International (MDPI)
record_format MEDLINE/PubMed
spelling pubmed-39753882014-04-04 Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model Noh, Dong-Hyung Lee, Eun-Joo Kim, Ah-Young Lee, Eun-Mi Min, Chang-Woo Kang, Kyung-Ku Lee, Myeong-Mi Kim, Sang-Hyeob Sung, Soo-Eun Hwang, Meeyul Yu, Dae-Yeul Jeong, Kyu-Shik Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2014-03-07 /pmc/articles/PMC3975388/ /pubmed/24608925 http://dx.doi.org/10.3390/ijms15034126 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Noh, Dong-Hyung
Lee, Eun-Joo
Kim, Ah-Young
Lee, Eun-Mi
Min, Chang-Woo
Kang, Kyung-Ku
Lee, Myeong-Mi
Kim, Sang-Hyeob
Sung, Soo-Eun
Hwang, Meeyul
Yu, Dae-Yeul
Jeong, Kyu-Shik
Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model
title Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model
title_full Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model
title_fullStr Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model
title_full_unstemmed Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model
title_short Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model
title_sort alcohol induced hepatic degeneration in a hepatitis c virus core protein transgenic mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975388/
https://www.ncbi.nlm.nih.gov/pubmed/24608925
http://dx.doi.org/10.3390/ijms15034126
work_keys_str_mv AT nohdonghyung alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT leeeunjoo alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT kimahyoung alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT leeeunmi alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT minchangwoo alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT kangkyungku alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT leemyeongmi alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT kimsanghyeob alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT sungsooeun alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT hwangmeeyul alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT yudaeyeul alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel
AT jeongkyushik alcoholinducedhepaticdegenerationinahepatitiscviruscoreproteintransgenicmousemodel