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

Ryan E. Forster, Peter W. Jurutka, Jui-Cheng Hsieh, Carol A. Haussler, Christine L. Lowmiller, Ichiro Kaneko, Mark R Haussler, G Kerr Whitfield

Research output: Contribution to journalArticle

84 Citations (Scopus)

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 -46kb) 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.

Original languageEnglish (US)
Pages (from-to)557-562
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume414
Issue number3
DOIs
StatePublished - Oct 28 2011

Fingerprint

Calcitriol Receptors
Vitamin D
Genes
Aging of materials
Kidney
Receptor, Fibroblast Growth Factor, Type 1
Ligands
Protein Isoforms
Membranes
Feedback
Messenger RNA
1,25-dihydroxyvitamin D
calcium phosphate

Keywords

  • Aging
  • Fibroblast growth factor 23
  • Kidney tubules, collecting
  • Kidney tubules, distal
  • Kidney tubules, proximal
  • Klotho protein
  • Receptors, calcitriol
  • Response elements
  • RNA splicing
  • Vitamin D

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. / Forster, Ryan E.; Jurutka, Peter W.; Hsieh, Jui-Cheng; Haussler, Carol A.; Lowmiller, Christine L.; Kaneko, Ichiro; Haussler, Mark R; Whitfield, G Kerr.

In: Biochemical and Biophysical Research Communications, Vol. 414, No. 3, 28.10.2011, p. 557-562.

Research output: Contribution to journalArticle

Forster, Ryan E. ; Jurutka, Peter W. ; Hsieh, Jui-Cheng ; Haussler, Carol A. ; Lowmiller, Christine L. ; Kaneko, Ichiro ; Haussler, Mark R ; Whitfield, G Kerr. / Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 414, No. 3. pp. 557-562.
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