title: Multiple faces of fibroblast growth factor-23.
abstract: This review examines the role of fibroblast growth factor-23 (FGF-23) in mineral metabolism, innate immunity and adverse cardiovascular outcomes.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Han
authors.forename: L Darryl
authors.initials: LD
authors.lastname: Quarles
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000276:immunology / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D007113:Immunity, Innate / Q000276:immunology*; D007668:Kidney / Q000378:metabolism*; D008903:Minerals / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; D008903:Minerals; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D012964:Sodium; D005966:Glucuronidase; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2