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Role of αKlotho and FGF23 in regulation of type II Na-dependent phosphate co-transporters

  • Ming Chang HuEmail author
  • Mingjun Shi
  • Orson W. MoeEmail author
Invited Review
  • 186 Downloads

Abstract

Alpha-Klotho is a member of the Klotho family consisting of two other single-pass transmembrane proteins: βKlotho and γKlotho; αKlotho has been shown to circulate in the blood. Fibroblast growth factor (FGF)23 is a member of the FGF superfamily of 22 genes/proteins. αKlotho serves as a co-receptor with FGF receptors (FGFRs) to provide a receptacle for physiological FGF23 signaling including regulation of phosphate metabolism. The extracellular domain of transmembrane αKlotho is shed by secretases and released into blood circulation (soluble αKlotho). Soluble αKlotho has both FGF23-independent and FGF23-dependent roles in phosphate homeostasis by modulating intestinal phosphate absorption, urinary phosphate excretion, and phosphate distribution into bone in concerted interaction with other calciophosphotropic hormones such as PTH and 1,25-(OH)2D. The direct role of αKlotho and FGF23 in the maintenance of phosphate homeostasis is partly mediated by modulation of type II Na+-dependent phosphate co-transporters in target organs. αKlotho and FGF23 are principal phosphotropic hormones, and the manipulation of the αKlotho-FGF23 axis is a novel therapeutic strategy for genetic and acquired phosphate disorders and for conditions with FGF23 excess and αKlotho deficiency such as chronic kidney disease.

Keywords

αKlotho FGF23 FGF receptor Phosphate homeostasis Na-dependent phosphate co-transporter 

Notes

Funding information

The authors acknowledge the grant support from the National Institutes of Health (NIDDK-R01-DK091392, NIDDK-R01-DK092461, NIDDK-R01-DK092461-6A1) and the George O’Brien Kidney Research Center at the University of Texas Southwestern Medical Center (NIDDK-P30-DK079328), the Charles and Jane Pak Center Innovative Research Support and Endowed Professor Collaborative Research Support, the Pak-Seldin Center for Metabolic and Clinical Research, and the Simmons Family Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Charles and Jane Pak Center for Mineral Metabolism and Clinical ResearchUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Department of PhysiologyUniversity of Texas Southwestern Medical CenterDallasUSA

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