Wikipedia

Fibroblast growth factor 23

(Redirected fromFGF23)

Fibroblast growth factor 23(FGF-23) is aproteinand member of thefibroblast growth factor(FGF) family which participates in the regulation ofphosphatein plasma andvitamin Dmetabolism. In humans it isencodedby theFGF23gene.FGF-23 decreases reabsorption of phosphate in the kidney. Mutations inFGF23can lead to its increased activity, resulting inautosomal dominant hypophosphatemic rickets.

FGF23
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesFGF23,ADHR, FGFN, HPDR2, HYPF, PHPTC, fibroblast growth factor 23, HFTC2
External IDsOMIM:605380;MGI:1891427;HomoloGene:10771;GeneCards:FGF23;OMA:FGF23 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

8074

64654

Ensembl

ENSG00000118972

ENSMUSG00000000182

UniProt

Q9GZV9

Q9EPC2

RefSeq (mRNA)

NM_020638

NM_022657

RefSeq (protein)

NP_065689

NP_073148

Location (UCSC)Chr 12: 4.37 – 4.38 MbChr 6: 127.05 – 127.06 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Description

edit

Fibroblast growth factor 23 (FGF23) is aproteinwhich in humans is encoded by theFGF23gene.[5]FGF23 is a member of thefibroblast growth factor(FGF) family which participates inphosphateandvitamin Dmetabolism and regulation.[6][7]

Function

edit

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 byosteocytesin response to increasedcalcitrioland phosphate.[8][9][10][11]FGF23 acts on the kidneys by decreasing the expression of NPT2, asodium-phosphate cotransporterin theproximal tubule.[12]

FGF23 may also suppress1-alpha-hydroxylase,reducing its ability to activatevitamin Dand subsequently impairing calcium absorption.[7][13]

Genetics

edit

In humans FGF23 is encoded by theFGF23gene,which is located onchromosome 12and is composed of threeexons.The gene was identified by its mutations associated withautosomal dominant hypophosphatemic rickets.[14]

Clinical significance

edit

Mutations inFGF23,which render the protein resistant to proteolytic cleavage, lead to its increased activity and torenalphosphate loss, in the human diseaseautosomal dominant hypophosphatemic rickets.

FGF23 can also be overproduced by some types oftumors,such as thebenignmesenchymalneoplasmphosphaturic mesenchymal tumorcausingtumor-induced osteomalacia,aparaneoplastic syndrome.[15][16]

Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumorcalcinosis.Mice lacking either FGF23 or theklothoenzyme 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 deficiencyand 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 osteomalaciaand Hypophosphatemic rickets with hypercalciuria.[18]

History

edit

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.

References

edit
  1. ^abcGRCh38: Ensembl release 89: ENSG00000118972–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000000182–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^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.
  6. ^Fukumoto S (2008)."Physiological regulation and disorders of phosphate metabolism--pivotal role of fibroblast growth factor 23".Internal Medicine.47(5): 337–343.doi:10.2169/internalmedicine.47.0730.PMID18310961.
  7. ^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.
  8. ^Dance A (23 February 2022)."Fun facts about bones: More than just scaffolding".Knowable Magazine.doi:10.1146/knowable-022222-1.S2CID247095495.Retrieved8 March2022.
  9. ^Robling AG, Bonewald LF (February 2020)."The Osteocyte: New Insights".Annual Review of Physiology.82(1): 485–506.doi:10.1146/annurev-physiol-021119-034332.PMC8274561.PMID32040934.
  10. ^Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro-O M, Huang CL (July 2008)."Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1".Proceedings of the National Academy of Sciences of the United States of America.105(28): 9805–9810.Bibcode:2008PNAS..105.9805C.doi:10.1073/pnas.0803223105.PMC2474477.PMID18606998.
  11. ^Brown RB, Razzaque MS (January 2018). "Chapter 31 - Endocrine Regulation of Phosphate Homeostasis". In Singh AK, Williams GH (eds.).Textbook of Nephro-Endocrinology(Second ed.). Academic Press. pp. 539–548.doi:10.1016/b978-0-12-803247-3.00032-5.hdl:10012/15679.ISBN978-0-12-803247-3.S2CID102827267.
  12. ^Jüppner H (April 2011)."Phosphate and FGF-23".Kidney International. Supplement.79(121): S24–S27.doi:10.1038/ki.2011.27.PMC3257051.PMID21346724.
  13. ^Rodríguez-Ortiz ME, Rodríguez M (2015)."FGF23 as a calciotropic hormone".F1000Research.4:1472.doi:10.12688/f1000research.7189.1.PMC4815615.PMID27081473.
  14. ^"Entrez Gene: FGF23 fibroblast growth factor 23".
  15. ^Zadik Y, Nitzan DW (February 2012). "Tumor induced osteomalacia: a forgotten paraneoplastic syndrome?".Oral Oncology.48(2): e9-10.doi:10.1016/j.oraloncology.2011.09.011.PMID21985764.
  16. ^Green D, Mohorianu I, Piec I, Turner J, Beadsmoore C, Toms A, et al. (December 2017)."MicroRNA expression in a phosphaturic mesenchymal tumour".Bone Reports.7:63–69.doi:10.1016/j.bonr.2017.09.001.PMC5596358.PMID28932769.
  17. ^Huang CL (May 2010)."Regulation of ion channels by secreted Klotho: mechanisms and implications".Kidney International.77(10): 855–860.doi:10.1038/ki.2010.73.PMID20375979.
  18. ^abBeck-Nielsen SS, Mughal Z, Haffner D, Nilsson O, Levtchenko E, Ariceta G, et al. (February 2019)."FGF23 and its role in X-linked hypophosphatemia-related morbidity".Orphanet Journal of Rare Diseases.14(1): 58.doi:10.1186/s13023-019-1014-8.PMC6390548.PMID30808384.
  19. ^David V, Martin A, Isakova T, Spaulding C, Qi L, Ramirez V, et al. (January 2016)."Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production".Kidney International.89(1): 135–146.doi:10.1038/ki.2015.290.PMC4854810.PMID26535997.
  20. ^Strewler GJ (May 2001)."FGF23, hypophosphatemia, and rickets: has phosphatonin been found?".Proceedings of the National Academy of Sciences of the United States of America.98(11): 5945–5946.doi:10.1073/pnas.11154898.PMC33399.PMID11371627.

Further reading

edit

This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Fibroblast_growth_factor_23&oldid=1254904802"