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Endothelin receptor B controls the production of fibroblast growth factor 23.
- Source :
-
FASEB Journal . May2020, Vol. 34 Issue 5, p6262-6270. 9p. - Publication Year :
- 2020
-
Abstract
- 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)2D3 concentrations were determined by ELISA, serum and urinary phosphate and Ca2+ 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)2D3 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 34
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 143042375
- Full Text :
- https://doi.org/10.1096/fj.201903109R