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 α₁ and β₁ 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 α₁ and 2.8-fold for β₁. The increase in mRNA was detected as early as 6 h for the β₁-subunit and 18 h for the α₁-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 α₁ and β₁ 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.