Na+-K+-ATPase gene regulation by glucocorticoids in a fetal lung epithelial cell line

The Na+ pump, Na+-K+-ATPase, along with the Na+ channel is essential for the removal of alveolar solute and fluid perinatally. Because Na+-pump mRNA and activity increase before birth and maternal glucocorticoids (GCs) influence Na+-K+-ATPase mRNA expression in fetal rat lung, we hypothesized that GCs increased Na+-K+-ATPase gene expression in a fetal lung epithelial cell line. After 24 h of exposure, dexamethasone increased the steady-state levels of Na+-K+-ATPase alpha(1) and beta(1) mRNA in a fetal rat lung epithelial cell line in a dose-dependent fashion (10(-7) to 10(-5) M). The maximal increase in mRNA levels was 3.8-fold for al and 2.8-fold for beta(1). The increase in mRNA was detected as early as 6 h for the beta(1)-subunit and 18 h for the alpha(1)-subunit, and both peaked at 24 h. This gene upregulation was not due to increased mRNA stability based on mRNA half-life determination after actinomycin D inhibition. Transfection experiments with alpha(1) and beta(1) promoter-reporter constructs demonstrated 3.2 +/- 0.5- and 2.6 +/- 0.4-fold increases, respectively, in promoter activity, consistent with transcriptional activation of the promoter-reporter construct. These findings, increased promoter activity with no change in stability, indicate that GCs increased Na+-K+-ATPase transcription in a fetal lung epithelial cell line.