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 language | English (US) |
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Pages (from-to) | 557-562 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 414 |
Issue number | 3 |
DOIs | |
State | Published - Oct 28 2011 |
Keywords
- Aging
- Fibroblast growth factor 23
- Kidney tubules, collecting
- Kidney tubules, distal
- Kidney tubules, proximal
- Klotho protein
- RNA splicing
- Receptors, calcitriol
- Response elements
- Vitamin D
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology