title: Fibroblast growth factor 23--structure, function and role in kidney diseases.
abstract: The fibroblast growth factor (FGF) family comprises a number of polypeptides which share a common homology core region. FGF-23, produced by osteoblasts and osteocytes, belongs to the FGF-19 subfamily and serves as the main phosphatonine. Two forms of circulating FGF-23 are detectable in serum: full-length FGF-23--intact FGF-23 (iFGF-23), which is biologically active, and the inactive C-terminal FGF-23 (cFGF-23). FGF-23 with a coreceptor (Klotho protein) inhibits renal phosphate reabsorption and synthesis of calcitriol by reducing 1alpha-hydroxylase (CYP27B1) activity, reducing vitamin D-dependent phosphate intestinal absorption. High phosphorus intake, 1,25-dihydroxyvitamin D3 and PTH are the main stimuli for FGF-23 secretion. Impaired FGF-23 metabolism is involved in phosphate disturbances manifesting as rickets or osteomalacia or increased tissue calcinosis. FGF-23 may be also produced by some tumors leading to hypophosphatemia. Both cFGF-23 and iFGF-23 concentrations start to increase with mild impairment of the glomerular filtration rate in stage 2 or 3 of chronic kidney disease (CKD) as a consequence of the increased FGF-23 production. It seems that enhanced FGF-23 secretion may constitute a protective mechanism against enhanced phosphate accumulation in the early stages of CKD. However, it may lead to calcitriol deficiency and escalation of secondary hyperparathyroidism. Increased FGF-23 level is supposed to be an independent factor increasing mortality of CKD patients. There is ambiguous data if FGF-23 only reflects disturbances in calcium-phosphate metabolism or if it exerts a detrimental effect itself by diminishing calcitriol synthesis, inducing cell proliferation or acting through low-affinity, Klotho-independent receptors in the heart and endothelium. So far, little evidence supports direct FGF-23 toxicity.
authors.affiliation: Department of Pathophysiology, Medical University of Silesia, Katowice, Poland. pkocelak@sum.edu.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Kocełak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Olszanecka-Glinianowicz
authors.forename: Jerzy
authors.initials: J
authors.lastname: Chudek
mesh_terms: D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000090265:Klotho Proteins; D011487:Protein Conformation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins