Large-scale gene profiling of the liver in a mouse model of chronic, intragastric ethanol infusion.
OBJECTIVE
The mechanisms underlying alcohol-induced liver injury are not fully elucidated. An approach in this direction would consist of an all-inclusive assessment of gene expression in the liver. The purpose of this study was to perform a comprehensive analysis of gene expression in the livers of mice treated with ethanol by means of intragastric infusion.


METHODS
An ethanol- or glucose-enriched liquid diet was fed to animals for 4 weeks via a long-term gastrostomy catheter. The animals were killed and plasma alanine:2-oxoglutarate aminotransferase (ALT) assay, liver histology and total RNA analysis by microarray gene technology were performed.


RESULTS
Alcohol increased ALT, induced steatosis, necrosis and inflammation. A total of 12,423 genes were analyzed for expression out of which 4867 were expressed by the liver. Alcohol repressed expression of 11 genes, induced expression of 13 genes, and up- or down-regulated expression of 44 and 42 genes >2-fold, respectively. Gene expression analysis identified several genes that have not previously been tested for alcohol effects.


CONCLUSIONS
This study: (i) expands the knowledge of mechanism(s) of action of ethanol; (ii) indicates novel pathways of ethanol action on the liver, and (iii) illustrates the utility of microarray gene analysis in hepatology research.
Deaciuc
Ion V
IV
Division of Gastroentrology/Hepatology, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA. i0deac01@gwise.louisville.edu
Doherty
Dennis E
DE
Burikhanov
Ravshan
R
Lee
Eun Y
EY
Stromberg
Arnold J
AJ
Peng
Xuejun
X
de Villiers
Willem J S
WJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D000431:Ethanol / Q000097:blood / Q000494:pharmacology; D005235:Fatty Liver, Alcoholic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D020411:Oligonucleotide Array Sequence Analysis
D002492:Central Nervous System Depressants; D000431:Ethanol; D000410:Alanine Transaminase