ACTIVATION BY ACETALDEHYDE OF THE PROMOTER OF THE MOUSE ALPHA(2)(I) COLLAGEN GENE WHEN TRANSFECTED INTO RAT ACTIVATED STELLATE CELLS

The effect of acetaldehyde in activating the mouse alpha(2)(I) collage n promoter in transiently transfected rat activated stellate cells and the possible mediating effect of transforming growth factor beta(1) ( TGF beta(1)) on type I collagen gene expression were determined. Aceta ldehyde and TGF beta(1), each had a similar effect in activating the w ild-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. Th e effects of acetaldehyde and TGF beta(1) are therefore mediated by a similar factor or factors that bind to the NF-I consensus sequence wit hin the region -352 to -104. Additional factors may also play a role i n the effects of acetaldehyde and TGF beta(1), which have similar effe cts on the wild-type promoter, but become additive in activating the p romoter with a more distal deletion containing a cis-repressor element . Pretreatment of activated stellate cells with antibodies to TGF beta (1) suppressed the effect of acetaldehyde in increasing the alpha(1)(I ) collagen message, indicating that TGF beta(1) mediates the effect of the acetaldehyde-induced increase in the expression of the alpha(1)(I ) collagen gene which also contains NF-I binding sites. (C) 1996 Acade mic Press, Inc.