Activation by acetaldehyde of the promoter of the mouse alpha2(I) collagen gene when transfected into rat activated stellate cells.
The effect of acetaldehyde in activating the mouse alpha2(I) collagen promoter in transiently transfected rat activated stellate cells and the possible mediating effect of transforming growth factor beta1 (TGFbeta1) on type I collagen gene expression were determined. Acetaldehyde and TGFbeta1, each had a similar effect in activating the wild-type promoter, but failed to activate the promoter with a -352 to -104 deletion, or the promoter containing a 3-bp substitution between -305 and -303 in the putative nuclear factor I (NF-I) binding site. The effects of acetaldehyde and TGFbeta1 are therefore mediated by a similar factor or factors that bind to the NF-I consensus sequence within the region -352 to -104. Additional factors may also play a role in the effects of acetaldehyde and TGFbeta1, which have similar effects on the wild-type promoter, but become additive in activating the promoter with a more distal deletion containing a cis-repressor element. Pretreatment of activated stellate cells with antibodies to TGFbeta1 suppressed the effect of acetaldehyde in increasing the alpha1(I) collagen message, indicating that TGFbeta1 mediates the effect of the acetaldehyde-induced increase in the expression of the alpha1(I) collagen gene which also contains NF-I binding sites.
Anania
F A
FA
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205-2195, USA.
Potter
J J
JJ
Rennie-Tankersley
L
L
Mezey
E
E
D000079:Acetaldehyde / Q000494:pharmacology*; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics*; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D000079:Acetaldehyde