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Chronic Ethanol Feeding Alters mi RNA Expression Dynamics During Liver Regeneration
Author(s) -
Dippold Rachael P.,
Vadigepalli Rajanikanth,
Gonye Gregory E.,
Patra Biswanath,
Hoek Jan B.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01852.x
Subject(s) - rna , liver regeneration , chromatin immunoprecipitation , microbiology and biotechnology , biology , gene expression , medicine , endocrinology , regeneration (biology) , promoter , biochemistry , gene
Background Adaptation to chronic ethanol ( E t OH ) 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 E t OH intake on hepatic microRNA (mi RNA ) expression in male S prague– D awley rats during the initial 24 hours of liver regeneration following 70% partial hepatectomy (PHx) using mi RNA microarrays. mi RNA expression during adaptation to E t OH was investigated using RT ‐q PCR . Nuclear factor kappa B ( NF κ B ) binding at target mi RNA promoters was investigated with chromatin immunoprecipitation. Results Unsupervised clustering of mi RNA expression profiles suggested that mi RNA expression was more affected by chronic E t OH feeding than by the acute challenge of liver regeneration after PH x. Several mi RNA s that were significantly altered by chronic E t OH feeding, including mi R ‐34a, mi R ‐103, mi R ‐107, and mi R ‐122 have been reported to play a role in regulating hepatic metabolism and the onset of these mi RNA changes occurred gradually during the time course of E t OH feeding. Chronic E t OH feeding also altered the dynamic mi RNA profile during liver regeneration. Promoter analysis predicted a role for NF κ B in the immediate‐early mi RNA response to PH x. NF κ B binding at target mi RNA promoters in the chronic E t OH ‐fed group was significantly altered and these changes directly correlated with the observed expression dynamics of the target mi RNA . Conclusions Chronic E t OH consumption alters the hepatic mi RNA expression profile such that the response of the metabolism‐associated mi RNA s occurs during long‐term adaptation to E t OH rather than as an acute transient response to E t OH metabolism. Additionally, the dynamic mi RNA program during liver regeneration in response to PH x is altered in the chronically E t OH ‐fed liver and these differences reflect, in part, differences in mi RNA expression between the E t OH ‐adapted and control livers at the baseline state prior to PH x.