Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 470, Issue 2, Pages 384-390Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.01.034
Keywords
1,25(OH)(2)D-3; Mineralocorticoid; Spironolactone; SOCE; Calcium; Orai1; NF kappa B
Categories
Funding
- Deutsche Forschungsgemeinschaft [La 315/15-1, Fo 695/1-1, Fo 695/1-2]
- National Center for Competence in Research NCCR Kidney
- Swiss National Science Foundation
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The fibroblast growth factor (FGF23) plasma level is high in cardiac and renal failure and is associated with poor clinical prognosis of these disorders. Both diseases are paralleled by hyperaldosteronism. Excessive FGF23 levels and hyperaldosteronism are further observed in Klotho-deficient mice. The present study explored a putative aldosterone sensitivity of Fgf23 transcription and secretion the putative involvement of the aldosterone sensitive serum & glucocorticoid inducible kinase SGK1, SGK1 sensitive transcription factor NF kappa B and store operated Ca2+ entry (SOCE). Serum FGF23 levels were determined by ELISA in mice following sham treatment or exposure to deoxycorticosterone acetate (DOCA) or salt depletion. In osteoblastic UMR106 cells transcript levels were quantified by qRT-PCR, cytosolic Ca2+ concentration utilizing Fura-2-fluorescence, and SOCE from Ca2+ entry following store depletion by thapsigargin. As a result, DOCA treatment and salt depletion of mice elevated the serum C terminal FGF23 concentration. In UMR106 cells aldosterone enhanced and spironolactone decreased SOCE. Aldosterone further increased Fgf23 transcript levels in UMR106 cells, an effect reversed by mineralocorticoid receptor blockers spironolactone and eplerenone, SGK1 inhibitor EMD638683, NF kappa B-inhibitor withaferin A, and Ca2+ channel blocker YM58483. In conclusion, Fgf23 expression is up regulated by aldosterone, an effect sensitive to SGK1, NF kappa B and store-operated Ca2+ entry. (C) 2016 Elsevier Inc. All rights reserved.
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