The differential effect of prostaglandin E2 on transforming growth factor-beta and insulin-induced collagen formation in lung fibroblasts

Abstract

We examined the effect of prostaglandin (PG) E2 on transforming growth factor-beta (TGF-beta) and insulin-stimulated collagen formation in lung fibroblast cultures. TGF-beta increased type I collagen production 2-3-fold as determined by the densitometric analysis of autoradiograms from polyacrylamide gels and by measuring the amount of nondialyzable hydroxyproline. This was associated with a 5-6-fold increase in alpha 1(I) mRNA levels. PGE2 at 10(-7) M strongly inhibited type I collagen formation in TGF-beta-stimulated cultures by 60-70%. PGE2 blocked collagen formation in TGF-beta-stimulated cultures by decreasing levels of alpha 1(I) gene expression. PGE2 inhibited alpha 1(I) gene expression in part through inhibition of transcription. In contrast, insulin increased type I collagen production 2-fold and was associated with a 30-40% increase in alpha 1(I) mRNA. Although PGE2 also decreased alpha 1(I) mRNA levels in insulin-treated cultures, PGE2 had no effect on collagen formation. Taken together, these results demonstrate that collagen formation may proceed through two distinct pathways. These two pathways are distinguishable by their sensitivity to PGE2 treatment and their relationship to increases in collagen mRNAs.