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 alpha(1) 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.
Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
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D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004848:Epithelium / Q000196:embryology; D005333:Fetus / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006207:Half-Life; D006706:Homeostasis / Q000502:physiology; D008168:Lung / Q000196:embryology*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase