RETINOIC ACID INCREASES ELASTIN IN NEONATAL RAT LUNG FIBROBLAST-CULTURES

The factors that regulate elastin synthesis during pulmonary alveolar septal formation have not been identified. Because maximal alveolar el astin synthesis occurs over a relatively brief period (postnatal days 4-14 in the rat), we hypothesized that changes in the local concentrat ions of factors that regulate elastin synthesis may precede or accompa ny this period. Because pulmonary retinoid stores decline just before the fourth postnatal day, we also hypothesized that this decline could be accompanied by the utilization of retinoic acid, one of the most b iologically active retinoids, in a regulatory process that increases e lastin synthesis. If these hypotheses are correct, then retinoic acid should increase elastin synthesis by pulmonary cells. Therefore, cultu res of neonatal rat lung fibroblasts were exposed to retinoic acid, an d elastin production was quantitated. Retinoic acid produced a two- to threefold increase in the steady-state level of elastin mRNA, in solu ble elastin, and in insoluble elastin. The transcriptional initiation rate of the elastin gene was 1.8-fold higher in nuclei that were isola ted from retinoic acid-treated cells than in nuclei that were isolated from control cells. This indicates that the increase in steady-state elastin mRNA results, at least partially, from an increase in elastin transcription. Lung fibroblasts that were isolated from 8-day-old rats , but not cultured, contained retinoic acid. These findings suggest th at retinoic acid is a potential regulator of elastin synthesis in deve loping pulmonary alveoli.