FGF23 promotes renal calcium reabsorption through the TRPV5 channel

Abstract

αKlotho is thought to activate the epithelial calcium channel Transient Receptor Potential Vanilloid‐5 (TRPV5) in distal renal tubules through its putative glucuronidase/sialidase activity, thereby preventing renal calcium loss. However, αKlotho also functions as the obligatory co‐receptor for fibroblast growth factor‐23 (FGF23), a bone‐derived phosphaturic hormone. Here, we show that renal calcium reabsorption and renal membrane abundance of TRPV5 are reduced in Fgf23 knockout mice, similar to what is seen in αKlotho knockout mice. We further demonstrate that αKlotho neither co‐localizes with TRPV5 nor is regulated by FGF23. Rather, apical membrane abundance of TRPV5 in renal distal tubules and thus renal calcium reabsorption are regulated by FGF23, which binds the FGF receptor‐αKlotho complex and activates a signaling cascade involving ERK1/2, SGK1, and WNK4. Our data thereby identify FGF23, not αKlotho, as a calcium‐conserving hormone in the kidney.

Cited by papers we hold 7

• FGF/FGFR signaling in health and disease · 2020
  No notice
• FGF23 and its role in X-linked hypophosphatemia-related morbidity · 2019
  No notice
• The FGF metabolic axis · 2019
  No notice
• FGF23 Actions on Target Tissues—With and Without Klotho · 2018
  No notice
• Physiological Actions of Fibroblast Growth Factor-23 · 2018
  No notice
• The role of klotho in chronic kidney disease · 2018
  No notice
• FGF23 regulates renal sodium handling and blood pressure · 2014
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.