Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)

Abstract Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH)2D3. It is known that FGF23 release is stimulated by aldosterone and extracellular volume depletion. To characterize this effect furt...

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Autores principales:	Ganesh Pathare, Manuel Anderegg, Giuseppe Albano, Florian Lang, Daniel G. Fuster
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2295b5afddb84cd3af8e7164228d69f4
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spelling	oai:doaj.org-article:2295b5afddb84cd3af8e7164228d69f42021-12-02T15:09:06ZElevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)10.1038/s41598-018-22041-12045-2322https://doaj.org/article/2295b5afddb84cd3af8e7164228d69f42018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-22041-1https://doaj.org/toc/2045-2322Abstract Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH)2D3. It is known that FGF23 release is stimulated by aldosterone and extracellular volume depletion. To characterize this effect further in a model of mild hypovolemia, we studied mice lacking the thiazide sensitive NaCl cotransporter (NCC). Our data indicate that NCC knockout mice (KO) have significantly higher FGF23, PTH and aldosterone concentrations than corresponding wild type (WT) mice. However, 1,25(OH)2D3, fractional phosphate excretion and renal brush border expression of the sodium/phosphate co-transporter 2a were not different between the two genotypes. In addition, renal expression of FGF23 receptor FGFR1 and the co-receptor Klotho were unaltered in NCC KO mice. FGF23 transcript was increased in the bone of NCC KO mice compared to WT mice, but treatment of primary murine osteoblasts with the NCC inhibitor hydrochlorothiazide did not elicit an increase of FGF23 transcription. In contrast, the mineralocorticoid receptor blocker eplerenone reversed excess FGF23 levels in KO mice but not in WT mice, indicating that FGF23 upregulation in NCC KO mice is primarily aldosterone-mediated. Together, our data reveal that lack of renal NCC causes an aldosterone-mediated upregulation of circulating FGF23.Ganesh PathareManuel AndereggGiuseppe AlbanoFlorian LangDaniel G. FusterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ganesh Pathare Manuel Anderegg Giuseppe Albano Florian Lang Daniel G. Fuster Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)
description	Abstract Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH)2D3. It is known that FGF23 release is stimulated by aldosterone and extracellular volume depletion. To characterize this effect further in a model of mild hypovolemia, we studied mice lacking the thiazide sensitive NaCl cotransporter (NCC). Our data indicate that NCC knockout mice (KO) have significantly higher FGF23, PTH and aldosterone concentrations than corresponding wild type (WT) mice. However, 1,25(OH)2D3, fractional phosphate excretion and renal brush border expression of the sodium/phosphate co-transporter 2a were not different between the two genotypes. In addition, renal expression of FGF23 receptor FGFR1 and the co-receptor Klotho were unaltered in NCC KO mice. FGF23 transcript was increased in the bone of NCC KO mice compared to WT mice, but treatment of primary murine osteoblasts with the NCC inhibitor hydrochlorothiazide did not elicit an increase of FGF23 transcription. In contrast, the mineralocorticoid receptor blocker eplerenone reversed excess FGF23 levels in KO mice but not in WT mice, indicating that FGF23 upregulation in NCC KO mice is primarily aldosterone-mediated. Together, our data reveal that lack of renal NCC causes an aldosterone-mediated upregulation of circulating FGF23.
format	article
author	Ganesh Pathare Manuel Anderegg Giuseppe Albano Florian Lang Daniel G. Fuster
author_facet	Ganesh Pathare Manuel Anderegg Giuseppe Albano Florian Lang Daniel G. Fuster
author_sort	Ganesh Pathare
title	Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)
title_short	Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)
title_full	Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)
title_fullStr	Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)
title_full_unstemmed	Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)
title_sort	elevated fgf23 levels in mice lacking the thiazide-sensitive nacl cotransporter (ncc)
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/2295b5afddb84cd3af8e7164228d69f4
work_keys_str_mv	AT ganeshpathare elevatedfgf23levelsinmicelackingthethiazidesensitivenaclcotransporterncc AT manuelanderegg elevatedfgf23levelsinmicelackingthethiazidesensitivenaclcotransporterncc AT giuseppealbano elevatedfgf23levelsinmicelackingthethiazidesensitivenaclcotransporterncc AT florianlang elevatedfgf23levelsinmicelackingthethiazidesensitivenaclcotransporterncc AT danielgfuster elevatedfgf23levelsinmicelackingthethiazidesensitivenaclcotransporterncc
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Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)

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