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

Pathare, Ganesh Tukaram; Anderegg, Manuel; Albano, Giuseppe; Lang, Florian; Fuster, Daniel Guido (2018). Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC). Scientific Reports, 8(1), p. 3590. Nature Publishing Group 10.1038/s41598-018-22041-1

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Fibroblast growth factor 23 (FGF23) participates in the orchestration of mineral metabolism by inducing phosphaturia and decreasing the production of 1,25(OH)D. 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)D, 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Pathare, Ganesh Tukaram; Anderegg, Manuel; Albano, Giuseppe and Fuster, Daniel Guido

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Daniel Guido Fuster

Date Deposited:

12 Apr 2018 15:22

Last Modified:

12 Apr 2018 15:22

Publisher DOI:

10.1038/s41598-018-22041-1

PubMed ID:

29483574

BORIS DOI:

10.7892/boris.112457

URI:

https://boris.unibe.ch/id/eprint/112457

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