Multiple faces of fibroblast growth factor-23

Curr Opin Nephrol Hypertens. 2016 Jul;25(4):333-42. doi: 10.1097/MNH.0000000000000240.


Purpose of review: This review examines the role of fibroblast growth factor-23 (FGF-23) in mineral metabolism, innate immunity and adverse cardiovascular outcomes.

Recent findings: FGF-23, produced by osteocytes in bone, activates FGFR/α-Klotho (α-Kl) complexes in the kidney. The resulting bone-kidney axis coordinates renal phosphate reabsorption with bone mineralization, and creates a counter-regulatory feedback loop to prevent vitamin D toxicity. FGF-23 acts to counter-regulate the effects of vitamin D on innate immunity and cardiovascular responses. FGF-23 is ectopically expressed along with α-Kl in activated macrophages, creating a proinflammatory paracrine signaling pathway that counters the antiinflammatory actions of vitamin D. FGF-23 also inhibits angiotensin-converting enzyme 2 expression and increases sodium reabsorption in the kidney, leading to hypertension and left ventricular hypertrophy. Finally, FGF-23 is purported to cause adverse cardiac and impair neutrophil responses through activation of FGFRs in the absence of α-Kl. Although secreted forms of α-Kl have FGF-23 independent effects, the possibility of α-Kl independent effects of FGF-23 is controversial and requires additional experimental validation.

Summary: FGF-23 participates in a bone-kidney axis regulating mineral homeostasis, proinflammatory paracrine macrophage signaling pathways, and in a bone-cardio-renal axis regulating hemodynamics that counteract the effects of vitamin D.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Bone and Bones / metabolism*
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / immunology
  • Fibroblast Growth Factors / metabolism*
  • Glucuronidase / metabolism
  • Homeostasis
  • Humans
  • Hypertension / metabolism*
  • Hypertrophy, Left Ventricular / metabolism*
  • Immunity, Innate / immunology*
  • Kidney / metabolism*
  • Minerals / metabolism
  • Osteocytes / metabolism
  • Peptidyl-Dipeptidase A / metabolism
  • Phosphates / metabolism
  • Signal Transduction
  • Sodium / metabolism
  • Vitamin D / metabolism


  • FGF23 protein, human
  • Minerals
  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Sodium
  • Glucuronidase
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2