Document Detail

Hepatitis C virus induces epithelial-mesenchymal transition in primary human hepatocytes.
MedLine Citation:
PMID:  23035229     Owner:  NLM     Status:  MEDLINE    
Hepatitis C virus (HCV)-mediated liver disease progression may reflect distinct molecular mechanisms for increased hepatocyte growth and hepatic stellate cell activation. In this study, we have observed that primary human hepatocytes, when infected in vitro with cell culture-grown HCV genotype 1a or 2a, display viral RNA and protein expression. Infected hepatocytes displayed a fibroblast-like shape and an extended life span. To understand the changes at the molecular level, we examined epithelial-mesenchymal transition (EMT) markers. Increased mRNA and protein expression levels of vimentin, snail, slug, and twist and a loss of the epithelial cell marker E-cadherin were observed. Snail and twist, when examined separately, were upregulated in chronically HCV-infected liver biopsy specimens, indicating an onset of an active EMT state in the infected liver. An increased expression level of fibroblast-specific protein 1 (FSP-1) in the infected hepatocytes was also evident, indicating a type 2 EMT state. Infected hepatocytes had significantly increased levels of phosphorylated β-catenin (Ser(552)) as an EMT mediator, which translocated into the nucleus and activated Akt. The phosphorylation level of β-catenin at Thr(41)/Ser(45) moieties was specifically higher in control than in HCV-infected hepatocytes, implicating an inactivation of β-catenin. Together, these results suggested that primary human hepatocytes infected with cell culture-grown HCV display EMT via the activation of the Akt/β-catenin signaling pathway. This observation may have implications for liver disease progression and therapeutic intervention strategies using inhibitory molecules.
Sandip K Bose; Keith Meyer; Adrian M Di Bisceglie; Ratna B Ray; Ranjit Ray
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-03
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-20     Completed Date:  2013-01-28     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13621-8     Citation Subset:  IM    
Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, Missouri, USA.
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MeSH Terms
Biological Markers / metabolism
Blotting, Western
Cell Line, Transformed
Epithelial-Mesenchymal Transition / physiology*
Fluorescent Antibody Technique
Hepacivirus / physiology*
Hepatocytes / cytology*,  virology
Proto-Oncogene Proteins c-akt / metabolism
beta Catenin / metabolism
Grant Support
Reg. No./Substance:
0/Biological Markers; 0/beta Catenin; EC Proteins c-akt

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