Cloning and expression of glucocorticoid-induced genes in fetal rat lung fibroblasts. Transforming growth factor-β3

Abstract

Glucocorticoids have been shown to accelerate fetal lung type II cell maturation, and this effect appears, in part, to be mediated via fibroblasts. To identify glucocorticoid induced genes in fetal lung fibroblasts, we screened a cDNA library from cortisol-treated fetal lung fibroblasts with a subtracted cDNA probe which was enriched for sequences specific for cortisol- treated fetal lung fibroblasts. Fifty-seven clones were isolated from the cDNA library. One cDNA represented ≃30% of the 57 clones. Analysis of DNA sequence homology suggested that this cDNA encodes the rat transforming growth factor-β3 (TGFβ3). We found that TGFβ3 mRNA was expressed in fetal lung fibroblasts but not epithelial cells. Expression of message in fetal lung fibroblasts was developmentally regulated. TGFβ3 mRNA levels were low during the pseudoglandular stage (day 18), peaked during the early canalicular stage of lung development (day 19), then fell again at days 20 and 21 (term = 22 days). Exposure of fetal lung fibroblasts to cortisol increased TGFβ3 mRNA expression in a time- and dose-dependent manner. Maternal administration of dexamethasone also enhanced mRNA expression of TGFβ3 in fetal lung fibroblasts. These data suggest that glucocorticoids may mediate their stimulatory effect on lung maturation by inducing TGFβ3 expression in fetal lung fibroblasts.