FGF23 promotes renal calcium reabsorption through the TRPV5 channel |
| |
| Authors: | Olena Andrukhova Alina Smorodchenko Monika Egerbacher Carmen Streicher Ute Zeitz Regina Goetz Victoria Shalhoub Moosa Mohammadi Elena E Pohl Beate Lanske Reinhold G Erben |
| |
| Institution: | 1. University of Veterinary Medicine Vienna, Vienna, Austria;2. New York University School of Medicine, New York, NY, USA;3. Amgen Inc., Thousand Oaks, CA, USA;4. Harvard School of Dental Medicine, Boston, MA, USA |
| |
| 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. |
| |
| Keywords: | calcium homeostasis fibroblast growth factor‐23 Klotho renal calcium reabsorption transient receptor potential vanilloid‐5 |
|
|
