Acetaldehyde activates the promoter of the mouse alpha 2(I) collagen gene.
The mechanism whereby ethanol ingestion results in hepatic fibrosis remains unknown. Acetaldehyde has been shown to increase alpha 1(I) collagen gene transcription in human fibroblasts and in rat myofibroblastlike cells (Ito cells) in culture. In this study, the effect of acetaldehyde was determined on the activation of the alpha 2(I) collagen promoter. A plasmid containing the mouse alpha 2(I) collagen promoter region (-2000 to 54), fused to the coding sequence of the reporter gene chloramphenicol acetyl transferase and similar plasmid constructs containing deletions in the collagen promoter, were transfected into NIH 3T3 fibroblasts in culture. Acetaldehyde (200 mumol/L) and transforming growth factor-beta 1 (5 ng/ml) activated the wild type promoter. The combination of acetaldehyde and transforming growth factor-beta 1 did not result in a greater effect than either alone. Acetaldehyde inhibited, whereas transforming growth factor-beta 1 did not activate, the promoter, with a -352 to -104 deletion. By contrast, acetaldehyde had no effect, whereas transforming growth factor-beta 1 resulted in a small decrease in the activity of the promoter, with a -501 to -352 deletion. This study shows that acetaldehyde and transforming growth factor-beta 1 independently activate the mouse alpha 2(I) collagen promoter and that this activation is mediated by the same proximal region of the promoter.
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Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Potter
J J
JJ
Rennie
L
L
Mezey
E
E
D000079:Acetaldehyde / Q000494:pharmacology*; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003094:Collagen / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D014162:Transfection
D003094:Collagen; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D015500:Chloramphenicol O-Acetyltransferase; D000079:Acetaldehyde