Phosphatidylinositol 3-kinase-dependent stabilization of alpha(1)(I) collagen mRNA in human lung fibroblasts

We investigated the role of phosphatidylinositol 3-kinase (PI3K) in the exp ression of alpha (1)(I) collagen mRNA. We report that the basal level of al pha (1)(I) collagen mRNA was reduced when PI3K activity was inhibited by ei ther LY-294002 or wortmannin. These PI3K inhibitors also blocked increases of alpha (1)(I) collagen mRNA levels after the addition of transforming gro wth factor-beta. The effect of PI3K inhibition was abolished by the removal of the inhibitor or by the addition of cycloheximide. Inhibition of PI3K a ctivity decreased the stability of the alpha (1)(I) collagen mRNA with no c hange in the rate of transcription of the alpha (1)(I) collagen gene as ass essed by Northern blotting with actinomycin D-treated fibroblasts and nucle ar run-on assays. Expression of a truncated alpha (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 i ncreased stabilization of alpha (1)(I) collagen mRNA. In vivo, the PI3K act ivity in fibroblasts may regulate basal levels of alpha (1)(I) collagen mRN A expression.