Activation by acetaldehyde of the promoter of the mouse α₂(I) collagen gene when transfected into rat activated stellate cells

The effect of acetaldehyde in activating the mouse α₂(I) collagen promoter in transiently transfected rat activated stellate cells and the possible mediating effect of transforming growth factor β₁ (TGFβ₁) on type I collagen gene expression were determined. Acetaldehyde and TGFβ₁, 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 TGFβ₁ 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 TGFβ₁, 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 TGFβ₁ suppressed the effect of acetaldehyde in increasing the α₁(I) collagen message, indicating that TGFβ₁ mediates the effect of the acetaldehyde- induced increase in the expression of the α₁(I) collagen gene which also contains NF-I binding sites.