RETINOIC ACID INCREASES SURFACTANT PROTEIN MESSENGER-RNA IN FETAL-RATLUNG IN CULTURE

Retinoic acid has both early or immediate (within hours) and late (aft er days) effects on gene expression. We studied the early effects of r etinoic acid on the surfactant protein (SP) genes. Exposure of fetal r at lung explants to all tl ans-retinoic acid for 4 h resulted in a sig nificant dose-dependent increase in SP-A, -B, and -C mRNA with markedl y different dose-response characteristics. The maximal (2.5x) increase in SP-A mRNA was observed with 10(-10) M retinoic acid, whereas treat ment with 10(-5) M resulted in a tendency to decreased levels. In cont rast, maximal stimulation of SP-C (6x) was noted at 10(-5) M. retinoic acid and that of SP-B (2x) at 10(-7) to 10(-5) M retinoic acid. Simil ar differences in the dose-response characteristics of SP-A and SP-C w ere observed with 9-cis-retinoic acid. A retinoic acid response elemen t consensus sequence was identified in the rat SP-A gene; we hypothesi ze that retinoic acid-receptor complexes act directly on the SP-A gene via this response element.