FGF23-Klotho signaling axis in the kidney

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Fibroblast growth factor-23 (FGF23) is a crucial bone-derived hormone.
• FGF23 mitigates hyperphosphatemia by regulating kidney phosphate and vitamin D.
• The kidney is a primary target organ for FGF23 signaling.

Purpose of the Study:

• To review recent advancements in FGF23-Klotho signaling within the kidney.
• To elucidate FGF23's distinct roles in proximal and distal renal tubules.

Main Methods:

• Review of current literature on FGF23-Klotho interactions in renal physiology.
• Analysis of molecular mechanisms underlying FGF23 actions in tubular epithelium.

Main Results:

• FGF23 independently affects proximal and distal tubular cells.
• In proximal tubules, FGF23 suppresses phosphate reabsorption via ERK1/2 and SGK1 activation, impacting sodium-phosphate cotransporters.
• In distal tubules, FGF23 enhances calcium and sodium reabsorption by upregulating TRPV5 and NCC expression through WNK4 activation.

Conclusions:

• FGF23 exerts distinct effects on renal tubular transport processes.
• FGF receptor-1 (FGFR1) complexed with Klotho is likely the key mediator.
• These newly identified functions of FGF23 have significant implications for chronic kidney disease and related disorders.