LM Brettell and SE McGowan
Veterans Affairs Medical Center, Iowa City, Iowa.

During pulmonary development, there is a burst in elastin synthesis by interstitial fibroblasts coincident with the period of alveolar septal elongation. Little is known about the regulation of elastin synthesis by these cells, although several endocrine and paracrine factors influence lung fibroblast elastin production. Because alveolar septal elongation is accompanied by a decrease in capillary endothelial cell mitosis, we have hypothesized that a reduction in basic fibroblast growth factor (bFGF), an endothelial cell mitogen, may occur concomitantly with an increase in elastin synthesis. This temporal relationship suggests that bFGF may influence elastin production by interstitial fibroblasts. Therefore, we have examined the effects of bFGF on elastin production by postconfluent, serum-free cultures of lipid interstitial fibroblasts (LF). Elastin production was quantitated by analyzing the incorporation of 3H-valine into the soluble elastin precursor tropoelastin (TE). Exogenous bFGF decreased the quantity of newly synthesized TE in the culture media and cell layers of LF. The level of newly synthesized TE in the media was decreased to 36% and 48% of the unexposed control when LF were exposed for 48 h to 10 or 75 ng/ml bFGF, respectively. Northern analysis demonstrated that the decrease in TE was accompanied by a similar decrease in elastin mRNA. Transient transfection experiments using an elastin promoter/CAT gene construct demonstrated that bFGF exposure decreased elastin promoter activity. These results suggest that bFGF decreases elastin transcription. Exposure to an anti-bFGF antibody neutralized endogenous bFGF and increased soluble elastin production by LF. Our studies indicate that exogenous and endogenous bFGF can suppress elastin production by LF. A similar effect may occur in the intact lung during development or chronic inflammation.

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