CLONING AND EXPRESSION OF GLUCOCORTICOID-INDUCED GENES IN PETAL RAT LUNG FIBROBLASTS - TRANSFORMING GROWTH FACTOR-BETA(3)

Glucocorticoids have been shown to accelerate fetal lung type II cell maturation, and this effect appears, in part, to be mediated via fibro blasts. To identify glucocorticoid induced genes in fetal lung fibrobl asts, we screened a cDNA Library from cortisol-treated fetal lung fibr oblasts with a subtracted cDNA probe which was enriched for sequences specific for cortisol-treated fetal lung fibroblasts. Fifty-seven clon es were isolated from the cDNA library. One cDNA represented approxima te to 30% of the 57 clones. Analysis of DNA sequence homology suggeste d that this cDNA encodes the rat transforming growth factor-beta(3) (T GF beta(3)). We found that TGF beta(3) mRNA was expressed in fetal lun g fibroblasts but not epithelial cells. Expression of message in fetal lung fibroblasts was developmentally regulated. TGF beta(3) mRNA leve ls were low during the pseudoglandular stage (day 18), peaked during t he early canalicular stage of lung development (day 19), then fell aga in at days 20 and 21 (term = 22 days). Exposure of fetal lung fibrobla sts to cortisol increased TGF beta(3) mRNA expression in a time- and d ose-dependent manner. Maternal administration of dexamethasone also en hanced mRNA expression of TGF beta(3) in fetal lung fibroblasts. These data suggest that glucocorticoids may mediate their stimulatory effec t on lung maturation by inducing TGF beta(3) expression in fetal lung fibroblasts.