Differential regulation of renal Klotho and FGFR1 in normal and uremic rats

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Juan R Muñoz-CastañedaMariano Rodriguez

Abstract

In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced. Uremic rats on a high-phosphate (HP) diet presented hyperphosphatemia with marked elevation of FGF23 and an increased fractional excretion of phosphate (P) that was associated with a marked reduction of Klotho expression and an increase in FGFR1. After neutralization of FGF23 by anti-FGF23 administration, phosphaturia was still abundant, Klotho expression remained low, and the FGFR1 level was reduced. These results suggest that the expression of renal Klotho is modulated by phosphaturia, whereas the FGFR1 expression is regulated by FGF23. Calcitriol (CTR) administration prevented a decrease in renal Klotho expression. In HEK293 cells HP produced nuclear translocation of β-catenin, together...Continue Reading

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Citations

Mar 27, 2019·Toxins·Cristian Rodelo-HaadMariano Rodriguez
Jun 1, 2018·Current Opinion in Nephrology and Hypertension·Reinhold G Erben
Dec 21, 2019·Clinical Science·Maria E Rodríguez-OrtizYolanda Almadén
Sep 3, 2020·European Journal of Clinical Nutrition·Lynda Ann FrassettoThomas Durward DuBose
Apr 3, 2020·Advances in Therapy·Mariano Rodríguez
Jul 24, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Javier A NeyraOrson W Moe
Sep 12, 2020·F1000Research·María E Rodríguez-Ortiz, Mariano Rodríguez
Nov 26, 2020·International Journal of Molecular Sciences·Maria L MaceEwa Lewin
Jan 28, 2021·Nutrients·María Victoria Pendón-Ruiz de MierMariano Rodríguez
Jan 11, 2021·Nefrología : publicación oficial de la Sociedad Española Nefrologia·María Luisa González-CasausAntonio Buño-Soto
Nov 4, 2020·Life Sciences·Ajinath KaleAnil Bhanudas Gaikwad
Sep 2, 2021·Nefrología : publicación oficial de la Sociedad Española Nefrologia·María Luisa González-CasausAntonio Buño-Soto

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