HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/3/L593    most recent 00037.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Hao, H. Articles by Ingbar, D. H. Search for Related Content PubMed PubMed Citation Articles by Hao, H. Articles by Ingbar, D. H.

Dexamethasone stimulates transcription of the Na⁺-K⁺-ATPase ₁ gene in adult rat lung epithelial cells

Department of Medicine, Pulmonary and Critical Care Division, University of Minnesota, Minneapolis, Minnesota 55455

Submitted 6 February 2003 ; accepted in final form 25 April 2003

Na⁺-K⁺-ATPase plays an essential role in active alveolar epithelial fluid resorption. In fetal and adult alveolar epithelial cells, glucocorticoids (GC) increase Na⁺-K⁺-ATPase activity and mRNA levels. We sought to define the mechanism of Na⁺-K⁺-ATPase gene upregulation by GC. In a rat alveolar epithelial cell line (RLE), dexamethasone (Dex) increased ₁-subunit Na⁺-K⁺-ATPase mRNA expression two- to threefold within 3 h after exposure to the GC. The increased gene expression was due to increased transcription as demonstrated by nuclear run-on assays, whereas mRNA stability remained unchanged. Transient transfection of 5' deletion mutants of a ₁ promoter-reporter construct demonstrated a 1.5- to 2.2-fold increase in promoter activity by Dex. All of the 5' deletion constructs contained partial or palindromic GC regulatory elements (GRE) and responded to GC. The increased expression of promoter reporter was inhibited by RU-486, a GC receptor (GR) antagonist, suggesting the involvement of GR. The palindromic GRE at -631 demonstrated Dex induction in a heterologous promoter construct. Gel mobility shift assays using RLE nuclear extracts demonstrated specific binding to this site and the presence of GR. We conclude that GC directly stimulate transcription of Na⁺-K⁺-ATPase ₁ gene expression in adult rat lung epithelial cells through a GR-dependent mechanism that can act at multiple sites.

sodium pump; glucocorticoid receptor; glucocorticoid response element; promoter; alveolar fluid; ion transport; type II cells

This article has been cited by other articles:

				K. Unfried, U. Sydlik, K. Bierhals, A. Weissenberg, and J. Abel Carbon nanoparticle-induced lung epithelial cell proliferation is mediated by receptor-dependent Akt activation Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L358 - L367. [Abstract] [Full Text] [PDF]

				S. R. Pondugula, N. N. Raveendran, Z. Ergonul, Y. Deng, J. Chen, J. D. Sanneman, L. G. Palmer, and D. C. Marcus Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat Physiol Genomics, January 12, 2006; 24(2): 114 - 123. [Abstract] [Full Text] [PDF]