FGF23´s main function is to regulate the phosphate concentration in plasma. It does this by decreasing reabsorption of phosphate in the kidney, which means phosphate is excreted in urine. FGF23 is secreted byosteocytes in response to increasedcalcitriol and phosphate.[8][9][10][11] FGF23 acts on the kidneys by decreasing the expression of NPT2, asodium-phosphate cotransporter in theproximal tubule.[12]
Mutations inFGF23, which render the protein resistant to proteolytic cleavage, lead to its increased activity and torenal phosphate loss, in the human diseaseautosomal dominant hypophosphatemic rickets.
Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumorcalcinosis. Mice lacking either FGF23 or theklotho enzyme age prematurely due tohyperphosphatemia.[17]
Over-expression of FGF23 has been associated with cardiovascular disease in chronic kidney disease including cardiomyocyte hypertrophy, vascular calcification, stroke, and endothelial dysfunction.[18]
FGF23 expression and cleavage is promoted byiron deficiency and inflammation.[19]
FGF23 is associated with at least 7 non-nutritional diseases of hypophosphatemia: aside from autosomal dominant hypophosphatemic rickets,X-linked hypophosphatemia, autosomal recessive hypophosphatemic rickets type 1, 2, and 3,Tumor-induced osteomalacia and Hypophosphatemic rickets with hypercalciuria.[18]
Prior to its discovery in 2000, it was hypothesized that a protein existed which performed the functions subsequently shown for FGF23. This putative protein was known as phosphatonin.[20] Several types of effects were described including impairment of sodium dependent phosphate transport in both intestinal and renal brush border membrane vesicles, inhibition of production of calcitriol, stimulation of breakdown of calcitriol, and inhibition of production/secretion of parathyroid hormone.
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Yamashita T, Yoshioka M, Itoh N (October 2000). "Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain".Biochemical and Biophysical Research Communications.277 (2):494–498.doi:10.1006/bbrc.2000.3696.PMID11032749.
^abPerwad F, Zhang MY, Tenenhouse HS, Portale AA (November 2007). "Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro".American Journal of Physiology. Renal Physiology.293 (5):F1577 –F1583.doi:10.1152/ajprenal.00463.2006.PMID17699549.S2CID20559055.
Silve C, Beck L (June 2002). "Is FGF23 the long sought after phosphaturic factor phosphatonin?".Nephrology, Dialysis, Transplantation.17 (6):958–961.doi:10.1093/ndt/17.6.958.PMID12032180.
Quarles LD (July 2003). "FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization".American Journal of Physiology. Endocrinology and Metabolism.285 (1):E1 –E9.doi:10.1152/ajpendo.00016.2003.PMID12791601.
Fukagawa M, Nii-Kono T, Kazama JJ (July 2005). "Role of fibroblast growth factor 23 in health and in chronic kidney disease".Current Opinion in Nephrology and Hypertension.14 (4):325–329.doi:10.1097/01.mnh.0000172717.49476.80.PMID15930999.S2CID23555353.
Imel EA, Econs MJ (September 2005). "Fibroblast growth factor 23: roles in health and disease".Journal of the American Society of Nephrology.16 (9):2565–2575.doi:10.1681/ASN.2005050573.PMID16033853.S2CID8612881.
Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, et al. (June 2001). "FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate".Biochemical and Biophysical Research Communications.284 (4):977–981.doi:10.1006/bbrc.2001.5084.PMID11409890.
Kruse K, Woelfel D, Strom TM (2002). "Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation".Hormone Research.55 (6):305–308.doi:10.1159/000050018 (inactive 1 November 2024).PMID11805436.S2CID46748089.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
