Mechanical strain and dexamethasone selectively increase surfactant protein C and tropoelastin gene expression

Physical forces derived from fetal breathing movements and hormones such as glucocorticoids are implicated in regulating fetal lung development. To el ucidate whether the different signaling pathways activated by physical and hormonal factors are integrated and coordinated at the cellular and transcr iptional levels, organotypic cultures of mixed fetal rat lung cells were su bjected to static culture or mechanical strain in the presence and absence of dexamethasone. Tropoelastin and collagen type I were used as marker gene s for fibroblasts, whereas surfactant protein (SP) A and SP-C were used as marker genes for distal epithelial cells. Mechanical strain, but not dexame thasone, significantly increased SP-C mRNA expression. Tropoelastin mRNA ex pression was upregulated by both mechanical strain and dexamethasone. No ad ditive or synergistic effect was observed when cells were subjected to mech anical stretch in the presence of dexamethasone. Neither mechanical strain nor dexamethasone alone or in combination had any significant effect on the expression of SP-A mRNA. Dexamethasone decreased collagen type I mRNA expr ession, whereas mechanical strain had no effect. The increases in tropoelas tin and SP-C mRNA levels induced by mechanical strain and/or dexamethasone were accompanied by increases in their heterogeneous nuclear RNA. In additi on, the stretch- and glucocorticoid-induced alterations in tropoelastin and SP-C mRNA expression were abrogated with 10 mu g/ml actinomycin D. These f indings suggest that tropoelastin and SP-C genes are selectively stimulated by physical and/or hormonal factors at the transcriptional level in fetal lung fibroblasts and distal epithelial cells, respectively.