Cell selective glucocorticoid induction of caveolin-1 and caveolae in differentiating pulmonary alveolar epithelial cell cultures

Barar, Jaleh, Campbell, Lee, Hollins, Andrew J., Thomas, Nicholas P.B., Smith, Mathew W., Morris, Christopher J. ORCID: https://orcid.org/0000-0002-7703-4474 and Gumbleton, Mark (2007) Cell selective glucocorticoid induction of caveolin-1 and caveolae in differentiating pulmonary alveolar epithelial cell cultures. Biochemical and Biophysical Research Communications, 359 (2). pp. 360-366. ISSN 0006-291X

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Increased caveolin-1 expression is a marker of the differentiation of lung alveolar epithelial type II cells into a type I phenotype. Here, we show in both a primary differentiating rat alveolar culture, and a human alveolar cell line (A549) that caveolae formation and caveolin-1 expression are dependent upon dexamethasone Dex, and is inhibited by the glucocorticoid receptor (GR) antagonist, mifepristone. Study of a panel of 20 different cell types showed the effect of (Dex) upon caveolin-1 expression to be highly cell selective for lung alveolar epithelial cells. The actions of glucocorticoid upon caveolin-1 appear indirect acting via intermediary genes as evidenced by cycloheximide (CHX) abolition of Dex-induced increases in caveolin-1 mRNA and by recombinant transfection studies using the caveolin-1 promoter cloned upstream of a reporter gene. Treatment with actinomycin D (ACD) revealed that the effects of Dex are also, at least in part, mediated by stabilisation of caveolin-1 mRNA. Collectively, these results indicate that glucocorticoids modulate the expression of caveolin-1 and caveolae biogenesis within alveolar epithelial cells via both transcriptional and translational modifications. The cell-selective effects of glucocorticoid upon caveolin may represent a previously unrecognised mechanism by which glucocorticoids affect lung development.

Item Type: Article
Uncontrolled Keywords: alveolar epithelium,caveolae,caveolin,dexamethasone,glucocorticoid,lung,pulmonary,biophysics,biochemistry,molecular biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1304
Faculty \ School: Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
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Depositing User: LivePure Connector
Date Deposited: 19 Jul 2022 17:30
Last Modified: 09 Apr 2023 00:24
URI: https://ueaeprints.uea.ac.uk/id/eprint/86653
DOI: 10.1016/j.bbrc.2007.05.106

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