Surfactant protein A (SPA) plays an important role in the function of pulmonary surfactant, a lipoprotein that prevents alveolar collapse at endexpiration by lowering the surface tension in the alveolus. We have shown in previous studies, using cultured human fetal lung explants, that when compared to SPA levels in control explants, accumulation of SPA mRNA and protein is inhibted by alltrans retinoic acid (RA), a ligand of the steroid hormone receptor family. Glucocorticoids are used clinically to accelerate fetal lung maturation, and have also been shown to regulate SPA mRNA levels in human fetal lung explants. In the human lung, SPA is the product of two genes, SPA1 and SPA2. We hypothesized that RA and glucocorticoids regulate both SPA genes in human fetal lung tissue. To test this hypothesis, we used primer extension analysis to evaluate the effects of RA and dexamethasone (DEX), a synthetic glucocorticoid, on the levels of the major SPA1 and SPA2 mRNA transcripts in cultured human fetal lung explants. In explants incubated in control medium for 6 days, the content of SPA1 mRNA was 2.7±0.8 times that of SPA2 mRNA (X±SEM, n=3). In explants treated with all trans RA (107M), the levels of total SPA mRNA were reduced by 41.9±0.9% (X±SEM, n=3). The relative amount of the major SPA1 transcript was reduced by 47.4±3.0%, and the major SPA2 transcript was reduced by 46.7±9.1% (X±SEM, n=3). In explants treated with DEX(107M), the levels of total SPA mRNA were reduced by 75.9±11.5%(X±SEM, n=3). The relative amount of the major SPA1 transcript was reduced by 70.0±10.0%, and the major SPA2 transcript was reduced by 79.7±0.4% (X±SEM, n=3), in DEX treated explants. These data suggest that in human fetal lung explants, retinoic acid and glucocorticoids inhibit the expression of both the SPA1 and SPA2 genes.
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Kumar, A., George, T. & Snyder, J. Retinoic acid and glucocorticoids inhibit the expression of both surfactant protein A (SPA) genes in human fetal lung explants. † 273. Pediatr Res 41, 48 (1997). https://doi.org/10.1203/00006450-199704001-00293