Endothelin receptor B controls the production of fibroblast growth factor 23

Endothelin-1 (ET-1) is a member of the endothelin family of peptide hormones first discovered as endothelium-derived mediators regulating vascular tone. ET-1 also regulates the proliferation and differentiation of bone cells that synthesize fibroblast growth factor 23 (FGF23). FGF23 is a hormone con...

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Bibliographic Details
Published inThe FASEB journal Vol. 34; no. 5; p. 6262
Main Authors Feger, Martina, Ewendt, Franz, Menzel, Matthias, Hocher, Berthold, Föller, Michael
Format Journal Article
LanguageEnglish
Published United States 01.05.2020
Subjects
Animals
Bone and Bones - metabolism
Calcium - metabolism
Female
Fibroblast Growth Factors - genetics
Fibroblast Growth Factors - metabolism
Gene Expression Regulation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphates - metabolism
Receptor, Endothelin B - physiology
phosphate
klotho
ET-1
vitamin D
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Summary:Endothelin-1 (ET-1) is a member of the endothelin family of peptide hormones first discovered as endothelium-derived mediators regulating vascular tone. ET-1 also regulates the proliferation and differentiation of bone cells that synthesize fibroblast growth factor 23 (FGF23). FGF23 is a hormone controlling renal phosphate and vitamin D metabolism. Here, we studied the role of ET-1 and endothelin receptor B (ETB) for FGF23 production. Fgf23 gene expression was studied in IDG-SW3 bone cells by quantitative RT-PCR. ETB-expressing (etb ) and rescued ETB-deficient mice (etb ) were studied in metabolic cages. Their serum FGF23, PTH, and 1,25(OH) D concentrations were determined by ELISA, serum and urinary phosphate and Ca by photometric methods. ET-1 and ETB agonist sarafotoxin 6c suppressed Fgf23 mRNA in IDG-SW3 cells. Serum C-terminal and intact FGF23 as well as bone Fgf23 mRNA levels were significantly higher in etb mice than in etb mice. Renal phosphate excretion was significantly higher in etb mice despite lower phosphate levels. In addition, etb animals exhibited calciuria and a significantly higher serum 1,25(OH) D concentration compared to etb mice. In conclusion, ETB-dependent ET-1 signaling is a potent suppressor of FGF23 formation. This effect is likely to be of clinical relevance given the use of endothelin receptor antagonists in various diseases.
ISSN:1530-6860
DOI:10.1096/fj.201903109R