Fetal rat lung fibroblasts produce a TGF beta homolog that blocks alveolar type II cell maturation

Normal growth and differentiation of the lung depends upon mesenchymal-epithelial interactions during development. Recombination experiments using immature (Day 17) and mature (Day 21) fetal rat lung fibroblasts (FRLF) revealed that the stimulatory effect of mature fibroblasts on fetal type II epithelial cells is blocked by immature fibroblasts. Similarly, conditioned medium from Day 17 FRLFs blocks the stimulatory effect (fibroblast-pneumonocyte factor) of Day 21 conditioned medium on type II epithelial cells. This blocking activity is nondialyzable, trypsin sensitive, and heat stable. Its activity is neutralized by an antibody to TGF beta, in both conditioned media and recombined cell studies, and its activity is mimicked by TGF beta. Developmentally, TGF beta-like activity is present in conditioned medium from 15- to 19-day FRLF, decreasing precipitously between 19 and 21 days gestation. Northern blot analysis of mRNAs from fetal rat lung fibroblasts on Days 17, 19, and 21 revealed expression of TGF beta at all three stages of development.