Document Detail


Chronic ethanol feeding alters miRNA expression dynamics during liver regeneration.
MedLine Citation:
PMID:  22823254     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Adaptation to chronic ethanol (EtOH) treatment of rats results in a changed functional state of the liver and greatly inhibits its regenerative ability, which may contribute to the progression of alcoholic liver disease.
METHODS: In this study, we investigated the effect of chronic EtOH intake on hepatic microRNA (miRNA) expression in male Sprague-Dawley rats during the initial 24 hours of liver regeneration following 70% partial hepatectomy (PHx) using miRNA microarrays. miRNA expression during adaptation to EtOH was investigated using RT-qPCR. Nuclear factor kappa B (NFκB) binding at target miRNA promoters was investigated with chromatin immunoprecipitation.
RESULTS: Unsupervised clustering of miRNA expression profiles suggested that miRNA expression was more affected by chronic EtOH feeding than by the acute challenge of liver regeneration after PHx. Several miRNAs that were significantly altered by chronic EtOH feeding, including miR-34a, miR-103, miR-107, and miR-122 have been reported to play a role in regulating hepatic metabolism and the onset of these miRNA changes occurred gradually during the time course of EtOH feeding. Chronic EtOH feeding also altered the dynamic miRNA profile during liver regeneration. Promoter analysis predicted a role for NFκB in the immediate-early miRNA response to PHx. NFκB binding at target miRNA promoters in the chronic EtOH-fed group was significantly altered and these changes directly correlated with the observed expression dynamics of the target miRNA.
CONCLUSIONS: Chronic EtOH consumption alters the hepatic miRNA expression profile such that the response of the metabolism-associated miRNAs occurs during long-term adaptation to EtOH rather than as an acute transient response to EtOH metabolism. Additionally, the dynamic miRNA program during liver regeneration in response to PHx is altered in the chronically EtOH-fed liver and these differences reflect, in part, differences in miRNA expression between the EtOH-adapted and control livers at the baseline state prior to PHx.
Authors:
Rachael P Dippold; Rajanikanth Vadigepalli; Gregory E Gonye; Biswanath Patra; Jan B Hoek
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-23
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  37 Suppl 1     ISSN:  1530-0277     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-10-17     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  E59-69     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 by the Research Society on Alcoholism.
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MeSH Terms
Descriptor/Qualifier:
Animals
Ethanol / administration & dosage*
Gene Expression Regulation* / drug effects
Liver Diseases, Alcoholic / genetics*,  physiopathology
Liver Regeneration / drug effects*,  genetics*
Male
MicroRNAs / biosynthesis*,  genetics
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
AA008714/AA/NIAAA NIH HHS; AA014986/AA/NIAAA NIH HHS; AA017261/AA/NIAAA NIH HHS; AA018873/AA/NIAAA NIH HHS; K05 AA017261/AA/NIAAA NIH HHS; R01 AA008714/AA/NIAAA NIH HHS; R01 AA018873/AA/NIAAA NIH HHS; R24 AA014986/AA/NIAAA NIH HHS; T32 AA007463/AA/NIAAA NIH HHS; T32 AA007467/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs; 3K9958V90M/Ethanol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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