GLUCOCORTICOID-INDUCED EFFECTS ON PATTERN-FORMATION AND EPITHELIAL-CELL DIFFERENTIATION IN EARLY EMBRYONIC RAT LUNGS

In this study, we examined the effects of dexamethasone (DEX) on airwa y branching and subsequent lung maturation. DEX treatment of fetal rat lung explants was initiated during the early pseudoglandular stage of development. Day 14 fetal lung explants were cultured with and withou t DEX for 4 d. Explants treated with 10 nM or higher concentrations of DEX showed features of both distorted and accelerated maturation. DEX -treated lungs had growth retardation, distorted branching, dilated pr oximal tubules, and suppressed proliferation of epithelial cells of th e distal tubules. Several biochemical and morphologic features of acce lerated maturation were also observed: I) the epithelial cells lining the distal tubules (prospective respiratory airways) were generally cu boidal or flattened; 2) the cuboidal cells often contained lamellar bo dies and abundant glycogen; 3) rudimentary septa and large airspace we re present; 4) mesenchymal tissue was attenuated and compressed betwee n adjacent epithelial tubules; 5) the distribution of SP-C mRNA in dis tal tubules was more mature, with individual and clusters of cells exp ressing SP-C transcripts; and 6) the transcript levels of several gene s related to epithelial growth keratinocyte growth factor (KGF), KGF r eceptor, and hepatocyte growth factor receptor] and differentiation [s urfactant proteins, SP-A, SP-B and SP-C and the Clara cell secretory p rotein, CC10] were precociously increased. These results show that DEX treatment of the lung during the early pseudoglandular stage accelera tes the acquisition of several features of advanced maturation that no rmally accompany late stages of fetal development. We postulate that K GF mediates at least some effects of DEX on lung maturation and gene e xpression.