Phosphatidylinositol 3-kinase-dependent stabilization of α1(I) collagen mRNA in human lung fibroblasts

We investigated the role of phosphatidylinositol 3-kinase (PI3K) in the expression of α 1 (I) collagen mRNA. We report that the basal level of α 1 (I) collagen mRNA was reduced when PI3K activity was inhibited by either LY-294002 or wortmannin. These PI3K inhibitors also blocked increases of α 1 (I) collagen mRNA levels after the addition of transforming growth factor-β. The effect of PI3K inhibition was abolished by the removal of the inhibitor or by the addition of cycloheximide. Inhibition of PI3K activity decreased the stability of the α 1 (I) collagen mRNA with no change in the rate of transcription of the α 1 (I) collagen gene as assessed by Northern blotting with actinomycin D-treated fibroblasts and nuclear run-on assays. Expression of a truncated α 1 (I) collagen minigene driven by a cytomegalovirus promoter in murine fibroblasts was decreased by LY-294002 treatment. These data indicate that PI3K activation results in increased stabilization of α 1 (I) collagen mRNA. In vivo, the PI3K activity in fibroblasts may regulate basal levels of α 1 (I) collagen mRNA expression.