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1(I) collagen mRNA in human lung fibroblasts
Pulmonary Center and Department of Biochemistry at Boston University School of Medicine and Boston Veterans Affairs Medical Center, Boston, Massachusetts 02118
We
investigated the role of phosphatidylinositol 3-kinase (PI3K) in the
expression of 
1(I) collagen mRNA. We report that the
basal level of 1(I) collagen mRNA was reduced when PI3K
activity was inhibited by either LY-294002 or wortmannin. These PI3K
inhibitors also blocked increases of 1(I) collagen mRNA
levels after the addition of transforming growth factor-
. 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 1(I) collagen mRNA with no change
in the rate of transcription of the 1(I) collagen gene
as assessed by Northern blotting with actinomycin D-treated fibroblasts
and nuclear run-on assays. Expression of a truncated
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 1(I) collagen mRNA. In vivo, the PI3K
activity in fibroblasts may regulate basal levels of
1(I) collagen mRNA expression.
mRNA stability; LY-294002; wortmannin; actinomycin D
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