Activation by Acetaldehyde of the Promoter of the Mouse alpha 2 (I) Collagen Gene When Transfected into Rat Activated Stellate Cells

Author： Anania F.A. Potter J.J. Rennie-Tankersley L. Mezey E.

Publisher： Elsevier

ISSN： 0003-9861

Source： Archives of Biochemistry and Biophysics, Vol.331, Iss.2, 1996-07, pp. : 187-193

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Abstract

The effect of acetaldehyde in activating the mouse alpha 2 (I) collagen promoter in transiently transfected rat activated stellate cells and the possible mediating effect of transforming growth factor beta 1 (TGFbeta 1 ) on type I collagen gene expression were determined. Acetaldehyde and TGFbeta 1 , 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 TGFbeta 1 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 TGFbeta 1 , 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 TGFbeta 1 suppressed the effect of acetaldehyde in increasing the alpha 1 (I) collagen message, indicating that TGFbeta 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.