Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis

Viral hepatitis resulting in chronic liver disease is an important clinical challenge and insight into the cellular processes that drive pathogenesis will be critical in order to develop new diagnostic and therapeutic options. Nuclear inclusions in viral and non-viral hepatitis are well documented a...

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Main Authors:	Thakur, Priyanka, Lamoke, Folami, Chaffin, Joanna M., Bartoli, Manuela, Lee, Jeffrey R., Duncan, Michael B.
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059674/

id	pubmed-4059674
recordtype	oai_dc
spelling	pubmed-40596742014-06-19 Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis Thakur, Priyanka Lamoke, Folami Chaffin, Joanna M. Bartoli, Manuela Lee, Jeffrey R. Duncan, Michael B. Research Article Viral hepatitis resulting in chronic liver disease is an important clinical challenge and insight into the cellular processes that drive pathogenesis will be critical in order to develop new diagnostic and therapeutic options. Nuclear inclusions in viral and non-viral hepatitis are well documented and have diagnostic significance in some disease contexts. However, the origins and functional consequences of these nuclear inclusions remain elusive. To date the clinical observation of nuclear inclusions in viral and non-viral hepatitis has not been explored at depth in murine models of liver disease. Herein, we report that in a transgenic model of hepatitis B surface antigen mediated hepatitis, murine hepatocytes exhibit nuclear inclusions. Cells bearing nuclear inclusions were more likely to express markers of cell proliferation. We also established a correlation between these inclusions and oxidative stress. N-acetyl cysteine treatment effectively reduced oxidative stress levels, relieved endoplasmic reticulum (ER) stress, and the number of nuclear inclusions we observed in the transgenic mice. Our results suggest that the presence of nuclear inclusions in hepatocytes correlates with oxidative stress and cellular proliferation in a model of antigen mediated hepatitis. Public Library of Science 2014-06-16 /pmc/articles/PMC4059674/ /pubmed/24932583 http://dx.doi.org/10.1371/journal.pone.0099872 Text en © 2014 Thakur et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Thakur, Priyanka Lamoke, Folami Chaffin, Joanna M. Bartoli, Manuela Lee, Jeffrey R. Duncan, Michael B.
spellingShingle	Thakur, Priyanka Lamoke, Folami Chaffin, Joanna M. Bartoli, Manuela Lee, Jeffrey R. Duncan, Michael B. Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis
author_facet	Thakur, Priyanka Lamoke, Folami Chaffin, Joanna M. Bartoli, Manuela Lee, Jeffrey R. Duncan, Michael B.
author_sort	Thakur, Priyanka
title	Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis
title_short	Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis
title_full	Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis
title_fullStr	Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis
title_full_unstemmed	Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis
title_sort	dysplastic hepatocytes develop nuclear inclusions in a mouse model of viral hepatitis
description	Viral hepatitis resulting in chronic liver disease is an important clinical challenge and insight into the cellular processes that drive pathogenesis will be critical in order to develop new diagnostic and therapeutic options. Nuclear inclusions in viral and non-viral hepatitis are well documented and have diagnostic significance in some disease contexts. However, the origins and functional consequences of these nuclear inclusions remain elusive. To date the clinical observation of nuclear inclusions in viral and non-viral hepatitis has not been explored at depth in murine models of liver disease. Herein, we report that in a transgenic model of hepatitis B surface antigen mediated hepatitis, murine hepatocytes exhibit nuclear inclusions. Cells bearing nuclear inclusions were more likely to express markers of cell proliferation. We also established a correlation between these inclusions and oxidative stress. N-acetyl cysteine treatment effectively reduced oxidative stress levels, relieved endoplasmic reticulum (ER) stress, and the number of nuclear inclusions we observed in the transgenic mice. Our results suggest that the presence of nuclear inclusions in hepatocytes correlates with oxidative stress and cellular proliferation in a model of antigen mediated hepatitis.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059674/
_version_	1612102092409798656

Dysplastic Hepatocytes Develop Nuclear Inclusions in a Mouse Model of Viral Hepatitis

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