title: Up-regulation of FGF23 release by aldosterone.
abstract: 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 NFκB and store operated Ca(2+) 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 Ca(2+) concentration utilizing Fura-2-fluorescence, and SOCE from Ca(2+) 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, NFκB-inhibitor withaferin A, and Ca(2+) channel blocker YM58483. In conclusion, Fgf23 expression is up-regulated by aldosterone, an effect sensitive to SGK1, NFκB and store-operated Ca(2+) entry.
authors.affiliation: Departments of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Departments of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors.forename: Anja T
authors.initials: AT
authors.lastname: Umbach
authors.affiliation: Departments of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Departments of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: Departments of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors.forename: Hajar
authors.initials: H
authors.lastname: Fakhri
authors.affiliation: Departments of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors.forename: Abul
authors.initials: A
authors.lastname: Fajol
authors.affiliation: Departments of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
authors.forename: Madhuri S
authors.initials: MS
authors.lastname: Salker
authors.affiliation: Institute of Physiology, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland; NCCR Kidney.CH, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Spichtig
authors.affiliation: Institute of Physiology, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland; NCCR Kidney.CH, Switzerland.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Daryadel
authors.affiliation: Institute of Physiology, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland; NCCR Kidney.CH, Switzerland.
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Von-Danckelmann-Platz 2, 06120 Halle (Saale), Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.affiliation: Departments of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany. Electronic address: florian.lang@uni-tuebingen.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C000717428:Fgf23 protein, mouse; D016328:NF-kappa B; D000450:Aldosterone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium
keywords: 1,25(OH)(2)D(3); Calcium; Mineralocorticoid; NFκB; Orai1; SOCE; Spironolactone