FGF23 and disorders of phosphate homeostasis.
It is well known that fibroblast growth factor (FGF) family members are associated with embryonic development and are critical for basic metabolic functions. This review will focus upon fibroblast growth factor-23 (FGF23) and its roles in disorders associated with phosphate handling. The discovery that mutations in FGF23 were responsible for the isolated renal phosphate wasting disorder autosomal dominant hypophosphatemic rickets (ADHR) has ascribed novel functions to the FGF family. FGF23 circulates in the bloodstream, and animal models demonstrate that FGF23 controls phosphate and Vitamin D homeostasis through the regulation of specific renal proteins. The ADHR mutations in FGF23 produce a protein species less susceptible to proteolytic processing. X-linked hypophosphatemic rickets (XLH), tumor-induced osteomalacia (TIO), and fibrous dysplasia of bone (FD) are disorders involving phosphate homeostasis that share phenotypes with ADHR, indicating that FGF23 may be a common denominator for the pathophysiology of these syndromes. Our understanding of FGF23 will help to develop novel therapies for phosphate wasting disorders, as well as for disorders of increased serum phosphate, such as tumoral calcinosis, a rare disorder, and renal failure, a common disorder.
Yu
Xijie
X
Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut St., IB130, Indianapolis, IN 46202, USA.
White
Kenneth E
KE
D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D005357:Fibrous Dysplasia of Bone / Q000235:genetics; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D008637:Mesenchymoma / Q000150:complications; D051379:Mice; D010018:Osteomalacia / Q000209:etiology; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D010710:Phosphates / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D011506:Proteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human; C506232:Phex protein, mouse