| First Author | Feger M | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 5 | Pages | 6262-6270 |
| PubMed ID | 32157737 | Mgi Jnum | J:307494 |
| Mgi Id | MGI:6707202 | Doi | 10.1096/fj.201903109R |
| Citation | Feger M, et al. (2020) Endothelin receptor B controls the production of fibroblast growth factor 23. FASEB J 34(5):6262-6270 |
| abstractText | 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)2 D3 concentrations were determined by ELISA, serum and urinary phosphate and Ca(2+) 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)2 D3 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. |
