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Biochem Biophys Res Commun. 2011 Oct 28;414(3):557-62. doi: 10.1016/j.bbrc.2011.09.117. Epub 2011 Oct 1.

Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells.

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  • 1Department of Basic Medical Sciences, University of Arizona College of Medicine - Phoenix, Phoenix, AZ 85004, USA. phxryan@gmail.com

Abstract

Isoforms of the mammalian klotho protein serve as membrane co-receptors that regulate renal phosphate and calcium reabsorption. Phosphaturic effects of klotho are mediated in cooperation with fibroblast growth factor receptor-1 and its FGF23 ligand. The vitamin D receptor and its 1,25-dihydroxyvitamin D(3) ligand are also crucial for calcium and phosphate regulation at the kidney and participate in a feedback loop with FGF23 signaling. Herein we characterize vitamin D receptor-mediated regulation of klotho mRNA expression, including the identification of vitamin D responsive elements (VDREs) in the vicinity of both the mouse and human klotho genes. In keeping with other recent studies of vitamin D-regulated genes, multiple VDREs control klotho expression, with the most active elements located at some distance (-31 to -46 kb) from the klotho transcriptional start site. We therefore postulate that the mammalian klotho gene is up-regulated by liganded VDR via multiple remote VDREs. The phosphatemic actions of 1,25-dihydroxyvitamin D(3) are thus opposed via the combined phosphaturic effects of FGF23 and klotho, both of which are upregulated by the liganded vitamin D receptor.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21982773
[PubMed - indexed for MEDLINE]
PMCID:
PMC3209523
Free PMC Article
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