BASIC FIBROBLAST GROWTH-FACTOR DECREASES ELASTIN PRODUCTION BY NEONATAL RAT LUNG FIBROBLASTS

During pulmonary development, there is a burst in elastin synthesis by interstitial fibroblasts coincident with the period of alveolar septa l elongation. Little is known about the regulation of elastin synthesi s by these cells, although several endocrine and paracrine factors inf luence lung fibroblast elastin production. Because alveolar septal elo ngation is accompanied by a decrease in capillary endothelial cell mit osis, we have hypothesized that a reduction in basic fibroblast growth factor (bFGF), an endothelial cell mitogen, may occur concomitantly w ith an increase in elastin synthesis. This temporal relationship sugge sts that bFGF may influence elastin production by interstitial fibrobl asts. Therefore, we have examined the effects of bFGF on elastin produ ction by postconfluent, serum-free cultures of lipid interstitial fibr oblasts (LF). Elastin production was quantitated by analyzing the inco rporation of H-3-valine into the soluble elastin precursor tropoelasti n (TE). Exogenous bFGF decreased the quantity of newly synthesized TE in the culture media and cell layers of LF. The level of newly synthes ized TE in the media was decreased to 36% and 48% of the unexposed con trol when LF were exposed for 48 h to 10 or 75 ng/ml bFGF, respectivel y. Northern analysis demonstrated that the decrease in TE was accompan ied by a similar decrease in elastin mRNA. Transient transfection expe riments using an elastin promoter/CAT gene construct demonstrated that bFGF exposure decreased elastin promoter activity. These results sugg est that bFGF decreases elastin transcription. Exposure to an anti-bFG F antibody neutralized endogenous bFGF and increased soluble elastin p roduction by LF. Our studies indicate that exogenous and endogenous bF GF can suppress elastin production by LF. A similar effect may occur i n the intact lung during development or chronic inflammation.