title: [FGF23 and Klotho: the new cornerstones of phosphate/calcium metabolism].
abstract: Since its first description as a phosphaturic agent in the early 2000s, fibroblast growth factor 23 (FGF23) has rapidly become the third key player of phosphate/calcium metabolism after PTH and vitamin D. FGF23 is a protein synthesized by osteocytes that acts mainly as a phosphaturic factor and a suppressor of 1α hydroxylase activity in the kidney. It inhibits the expression of type IIa and IIc sodium-phosphate cotransporters on the apical membrane of proximal tubular cells, thus leading to inhibition of phosphate reabsorption. Moreover, it also inhibits 1α hydroxylase activity. These two renal pathways account together for the hypophosphatemic effect of FGF23, but FGF23 has also been recently described as an inhibiting factor for PTH synthesis. Its exact role in bone remains to be defined. A transmembrane protein, Klotho, is an essential cofactor for FGF23 biological activity, but it can also act by itself for calcium and PTH regulation. This paper gives an overview of these recent data of phosphate/calcium physiology, as well as a description of clinical conditions associated with FGF23 deregulation (genetic diseases and chronic kidney disease). As a conclusion, future therapeutic consequences of the FGF23/Klotho axis are discussed.
authors.affiliation: Centre de référence des maladies rénales rares, hôpital Femme-Mère-Enfant, boulevard Pinel, 69677 Bron cedex, France.
authors.forename: J
authors.initials: J
authors.lastname: Bacchetta
authors.forename: P
authors.initials: P
authors.lastname: Cochat
authors.forename: I B
authors.initials: IB
authors.lastname: Salusky
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005966:Glucuronidase / Q000502:physiology*; D006801:Humans; D000090265:Klotho Proteins; D010710:Phosphates / Q000378:metabolism*
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium