Gene expression patterns of the liver in response to alcohol: in vivo and in vitro models compared.
Two basic models of alcoholic liver disease pathogenesis exist, one in vivo and one in vitro. To justify the in vitro model, evidence is needed to show that it stimulates the in vivo model. Therefore, changes in gene expression caused by high ethanol level were compared using the two models. Many functional pathways were upregulated in both models. These included the insulin signaling pathway, TGFbeta signaling pathway, apoptosis, MAPK signaling pathway, wnt signaling pathway and apoptosis. Differences were found in the fatty acids synthesis pathway, which was upregulated in vivo; and glycosylation enzymes which were downregulated in vivo. Also, downregulated in vitro were beta oxidation by mitochondria and translation factors. Catalase and superoxide dismutase in mitochondria were upregulated in vitro. These two enzymes have antioxidant effects. In summary, remarkably similar responses to high alcohol levels in the form of changes in gene expression pathways were found in the in vivo and in vitro models tested.
Bardag-Gorce
Fawzia
F
Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
French
Barbara A
BA
Dedes
Jennifer
J
Li
Jun
J
French
Samuel W
SW
D000818:Animals; D045744:Cell Line, Tumor; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D000431:Ethanol