Fibroblast growth factor 23: Difference between revisions

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{{Infobox_gene}}
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'''Fibroblast growth factor 23''' or '''FGF23''' is a [[protein]] that in humans is encoded by the ''FGF23'' [[gene]].<ref name="pmid11032749">{{cite journal | vauthors = Yamashita T, Yoshioka M, Itoh N | title = Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain | journal = Biochem. Biophys. Res. Commun. | volume = 277 | issue = 2 | pages = 494–8 | date = October 2000 | pmid = 11032749 | doi = 10.1006/bbrc.2000.3696 }}</ref> FGF23 is a member of the [[fibroblast growth factor]] (FGF) family which is responsible for [[phosphate]] and [[vitamin D]] metabolism.<ref name="pmid18310961">{{cite journal | vauthors = Fukumoto S | title = Physiological regulation and disorders of phosphate metabolism--pivotal role of fibroblast growth factor 23 | journal = Intern. Med. | volume = 47 | issue = 5 | pages = 337–43 | year = 2008 | pmid = 18310961 | doi = 10.2169/internalmedicine.47.0730 }}</ref><ref name="pmid17699549" />
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_FGF23_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2p39.
| PDB = {{PDB2|2p39}}
| Name = Fibroblast growth factor 23
| HGNCid = 3680
| Symbol = FGF23
| AltSymbols =; ADHR; HYPF; HPDR2; PHPTC
| OMIM = 605380
| ECnumber =
| Homologene = 10771
| MGIid = 1891427
| GeneAtlas_image1 = PBB_GE_FGF23_221166_at_tn.png
| Function = {{GNF_GO|id=GO:0008083 |text = growth factor activity}}  
| Component = {{GNF_GO|id=GO:0005615 |text = extracellular space}}
| Process = {{GNF_GO|id=GO:0030154 |text = cell differentiation}} {{GNF_GO|id=GO:0030500 |text = regulation of bone mineralization}} {{GNF_GO|id=GO:0030643 |text = cellular phosphate ion homeostasis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 8074
    | Hs_Ensembl = ENSG00000118972
    | Hs_RefseqProtein = NP_065689
    | Hs_RefseqmRNA = NM_020638
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 4347654
    | Hs_GenLoc_end = 4359155
    | Hs_Uniprot = Q9GZV9
    | Mm_EntrezGene = 64654
    | Mm_Ensembl = ENSMUSG00000000182
    | Mm_RefseqmRNA = XM_001003443
    | Mm_RefseqProtein = XP_001003443
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 127038593
    | Mm_GenLoc_end = 127046844
    | Mm_Uniprot = Q0VBJ8
  }}
}}
'''Fibroblast growth factor 23''' or '''FGF23''' is [[gene]] which is a member of the [[fibroblast growth factor]] (FGF) family and encodes a protein which is responsible for [[phosphate]] metabolism.


FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including [[embryonic development]], [[cell growth]], [[morphogenesis]], tissue repair, tumor growth and invasion. The product of this gene inhibits renal tubular phosphate transport.
== Function ==


FGF23 is located on [[chromosome 12]] and is composed of three [[exon]]s. Mutations in FGF23 which cause failure of proper [[gene splicing]] leads to increased activity of FGF23 and the [[kidney|renal]] phosphate loss found in the human disease [[autosomal dominant hypophosphatemic rickets]]. FGF23 is also overproduced by some types of [[tumor]]s, causing [[tumor-produced osteomalacia]]. Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of [[familial tumor calcinosis]].  
The main function of FGF23 seems to be regulation of phosphate concentration in plasma. FGF23 is secreted by [[osteocyte]]s in response to elevated [[calcitriol]]. FGF23 acts on the kidneys, where it decreases the expression of NPT2, a [[sodium/phosphate cotransporter|sodium-phosphate cotransporter]] in the proximal tubule.<ref name="pmid21346724">{{cite journal | vauthors = Jüppner H | title = Phosphate and FGF-23 | journal = Kidney Int. Suppl. | volume = 79| issue = 121 | pages = S24–7 | year = 2011 | pmid = 21346724 | pmc = 3257051 | doi = 10.1038/ki.2011.27 }}</ref> Thus, FGF23 decreases the reabsorption and increases excretion of phosphate. FGF23 may also suppress [[25-Hydroxyvitamin D3 1-alpha-hydroxylase|1-alpha-hydroxylase]], reducing its ability to activate [[vitamin D]] and subsequently impairing calcium absorption.<ref name="pmid17699549">{{cite journal | vauthors = Perwad F | title = Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro | journal = Am J Physiol Renal Physiol | volume = 293| issue =  5| pages = F1577–83 | year = 2007 | pmid = 17699549 | pmc =  | doi =  10.1152/ajprenal.00463.2006}}</ref><ref name="pmid27081473">{{cite journal | vauthors = Rodríguez-Ortiz ME, Rodríguez M | title = FGF23 as a calciotropic hormone | journal = F1000Research | volume = 4 | issue = | pages = 1472 | year = 2015 | pmid = 27081473 | pmc = 4815615 | doi = 10.12688/f1000research.7189.1 }}</ref>


There is evidence for a hormone/enzyme/extracellular matrix protein cascade involving [[fibroblastic growth factor 23]] (FGF23), the X-linked phosphate regulating endopeptidase homolog (PHEX), and a matrix extracellular phosphoglycoprotein (MEPE) that regulates systemic [[phosphate homeostasis]] and mineralization.<ref name=Quarles>{{ cite journal |author=Quarles LD |title=FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization |journal=Am J Physiol Endocrinol Metab. |month=Jul |year=2003 |volume=285 |issue=1 |pages=E1-9 |pmid=12791601 }}</ref> Short-term infusion of MEPE inhibits phosphate absorption in the jejunum but not the duodenum.<ref name=Marks>{{ cite journal |author=Marks J, Churchill LJ, Debnam ES, Unwin RJ |title=Matrix extracellular phosphoglycoprotein inhibits phosphate transport |journal=J Am Soc Nephrol. |year=2008 |month=Dec |volume=19 |issue=12 |pages=2313-20 |pmid=19005008 }}</ref> The short-term inhibitory effect of MEPE on renal and intestinal phosphate handling occurs without any changes in circulating levels of parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, or [[fibroblast growth factor 23]] (FGF23).<ref name=Marks/> MEPE may be involved in [[phosphate homeostasis]], acting in both the kidney and the gastrointestinal tract.<ref name=Marks/>
== Clinical significance ==


This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets.<ref name="entrez">{{cite web | title = Entrez Gene: FGF23 fibroblast growth factor 23| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8074| accessdate = }}</ref> Prior to discovery in 2000, it was hypothesized that a protein existed which performed the function of FGF23. This putative protein was known as phosphatonin.
''FGF23'' is located on [[chromosome 12]] and is composed of three [[exon]]s. Mutations in ''FGF23'' that render the protein resistant to proteolytic cleavage leads to increased activity of FGF23 and the [[kidney|renal]] phosphate loss found in the human disease [[autosomal dominant hypophosphatemic rickets]]. FGF23 is also overproduced by some types of [[tumor]]s, such as the [[benign]] [[mesenchymal]] [[neoplasm]] [[Phosphaturic mesenchymal tumor]] causing [[tumor-induced osteomalacia]], a [[paraneoplastic syndrome]].<ref name="TIO">{{cite journal | vauthors = Zadik Y, Nitzan DW | title = Tumor induced osteomalacia: A forgotten paraneoplastic syndrome? | journal = Oral Oncol | volume = 48 | issue = 2 | pages = e9–10 | date = October 2011 | pmid = 21985764 | doi = 10.1016/j.oraloncology.2011.09.011 }}</ref>


==References==
Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor [[calcinosis]].  This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets.<ref name="entrez">{{cite web | title = Entrez Gene: FGF23 fibroblast growth factor 23| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8074| accessdate = }}</ref>
{{reflist|2}}
 
==Further reading==
==History==
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.<ref>{{cite journal|last1=Strewler|first1=GJ|title=FGF23, hypophosphatemia, and rickets: has phosphatonin been found?|journal=Proceedings of the National Academy of Sciences of the United States of America|date=22 May 2001|volume=98|issue=11|pages=5945–6|doi=10.1073/pnas.11154898|pmid=11371627|pmc=33399}}</ref>  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 ==
{{reflist}}
{{Clear}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Kiela PR, Ghishan FK | title = Recent advances in the renal-skeletal-gut axis that controls phosphate homeostasis | journal = Lab. Invest. | volume = 89 | issue = 1 | pages = 7–14 | date = January 2009 | pmid = 19029978 | pmc = 4292907 | doi = 10.1038/labinvest.2008.114 }}
| citations =  
* {{cite journal | vauthors = Silve C, Beck L | title = Is FGF23 the long sought after phosphaturic factor phosphatonin? | journal = Nephrol. Dial. Transplant. | volume = 17 | issue = 6 | pages = 958–61 | year = 2003 | pmid = 12032180 | doi = 10.1093/ndt/17.6.958 }}
*{{cite journal | author=Silve C, Beck L |title=Is FGF23 the long sought after phosphaturic factor phosphatonin? |journal=Nephrol. Dial. Transplant. |volume=17 |issue= 6 |pages= 958-61 |year= 2003 |pmid= 12032180 |doi= }}
* {{cite journal | vauthors = Quarles LD | title = FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization | journal = Am. J. Physiol. Endocrinol. Metab. | volume = 285 | issue = 1 | pages = E1–9 | year = 2003 | pmid = 12791601 | doi = 10.1152/ajpendo.00016.2003 }}
*{{cite journal | author=Quarles LD |title=FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. |journal=Am. J. Physiol. Endocrinol. Metab. |volume=285 |issue= 1 |pages= E1-9 |year= 2003 |pmid= 12791601 |doi= 10.1152/ajpendo.00016.2003 }}
* {{cite journal | vauthors = Fukagawa M, Nii-Kono T, Kazama JJ | title = Role of fibroblast growth factor 23 in health and in chronic kidney disease | journal = Curr. Opin. Nephrol. Hypertens. | volume = 14 | issue = 4 | pages = 325–9 | year = 2005 | pmid = 15930999 | doi = 10.1097/01.mnh.0000172717.49476.80 }}
*{{cite journal | author=Fukagawa M, Nii-Kono T, Kazama JJ |title=Role of fibroblast growth factor 23 in health and in chronic kidney disease. |journal=Curr. Opin. Nephrol. Hypertens. |volume=14 |issue= 4 |pages= 325-9 |year= 2005 |pmid= 15930999 |doi= }}
* {{cite journal | vauthors = Imel EA, Econs MJ | title = Fibroblast growth factor 23: roles in health and disease | journal = J. Am. Soc. Nephrol. | volume = 16 | issue = 9 | pages = 2565–75 | year = 2006 | pmid = 16033853 | doi = 10.1681/ASN.2005050573 }}
*{{cite journal | author=Imel EA, Econs MJ |title=Fibroblast growth factor 23: roles in health and disease. |journal=J. Am. Soc. Nephrol. |volume=16 |issue= 9 |pages= 2565-75 |year= 2006 |pmid= 16033853 |doi= 10.1681/ASN.2005050573 }}
* {{cite journal | vauthors = Liu S, Quarles LD | title = How fibroblast growth factor 23 works | journal = J. Am. Soc. Nephrol. | volume = 18 | issue = 6 | pages = 1637–47 | year = 2007 | pmid = 17494882 | doi = 10.1681/ASN.2007010068 }}
*{{cite journal | author=Liu S, Quarles LD |title=How fibroblast growth factor 23 works. |journal=J. Am. Soc. Nephrol. |volume=18 |issue= 6 |pages= 1637-47 |year= 2007 |pmid= 17494882 |doi= 10.1681/ASN.2007010068 }}
* {{cite journal | vauthors = Econs MJ | title = Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23 | journal = Nat. Genet. | volume = 26 | issue = 3 | pages = 345–8 | year = 2000 | pmid = 11062477 | doi = 10.1038/81664 }}
*{{cite journal | author=Yamashita T, Yoshioka M, Itoh N |title=Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. |journal=Biochem. Biophys. Res. Commun. |volume=277 |issue= 2 |pages= 494-8 |year= 2000 |pmid= 11032749 |doi= 10.1006/bbrc.2000.3696 }}
* {{cite journal | vauthors = White KE, Jonsson KB, Carn G, Hampson G, Spector TD, Mannstadt M, Lorenz-Depiereux B, Miyauchi A, Yang IM, Ljunggren O, Meitinger T, Strom TM, Jüppner H, Econs MJ | title = The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting | journal = J. Clin. Endocrinol. Metab. | volume = 86 | issue = 2 | pages = 497–500 | year = 2001 | pmid = 11157998 | doi = 10.1210/jc.86.2.497}}
*{{cite journal  | author= |title=Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. |journal=Nat. Genet. |volume=26 |issue= 3 |pages= 345-8 |year= 2000 |pmid= 11062477 |doi= 10.1038/81664 }}
* {{cite journal | vauthors = Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T | title = Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 11 | pages = 6500–5 | year = 2001 | pmid = 11344269 | pmc = 33497 | doi = 10.1073/pnas.101545198 | bibcode = 2001PNAS...98.6500S}}
*{{cite journal | author=White KE, Jonsson KB, Carn G, ''et al.'' |title=The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue= 2 |pages= 497-500 |year= 2001 |pmid= 11157998 |doi= }}
* {{cite journal | vauthors = Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, Schiavi SC | title = FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate | journal = Biochem. Biophys. Res. Commun. | volume = 284 | issue = 4 | pages = 977–81 | year = 2001 | pmid = 11409890 | doi = 10.1006/bbrc.2001.5084}}
*{{cite journal | author=Shimada T, Mizutani S, Muto T, ''et al.'' |title=Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 11 |pages= 6500-5 |year= 2001 |pmid= 11344269 |doi= 10.1073/pnas.101545198 }}
* {{cite journal | vauthors = White KE, Carn G, Lorenz-Depiereux B, Benet-Pages A, Strom TM, Econs MJ | title = Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23 | journal = Kidney Int. | volume = 60 | issue = 6 | pages = 2079–86 | year = 2002 | pmid = 11737582 | doi = 10.1046/j.1523-1755.2001.00064.x}}
*{{cite journal | author=Bowe AE, Finnegan R, Jan de Beur SM, ''et al.'' |title=FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. |journal=Biochem. Biophys. Res. Commun. |volume=284 |issue= 4 |pages= 977-81 |year= 2001 |pmid= 11409890 |doi= 10.1006/bbrc.2001.5084 }}
* {{cite journal | vauthors = Kruse K, Woelfel D, Strom TM, Storm TM | title = Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation | journal = Horm. Res. | volume = 55 | issue = 6 | pages = 305–8 | year = 2002 | pmid = 11805436 | doi = 10.1159/000050018 }}
*{{cite journal | author=White KE, Carn G, Lorenz-Depiereux B, ''et al.'' |title=Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. |journal=Kidney Int. |volume=60 |issue= 6 |pages= 2079-86 |year= 2002 |pmid= 11737582 |doi= 10.1046/j.1523-1755.2001.00064.x }}
* {{cite journal | vauthors = Yamashita T, Konishi M, Miyake A, Inui K, Itoh N | title = Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway | journal = J. Biol. Chem. | volume = 277 | issue = 31 | pages = 28265–70 | year = 2002 | pmid = 12032146 | doi = 10.1074/jbc.M202527200}}
*{{cite journal | author=Kruse K, Woelfel D, Strom TM, Storm TM |title=Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation. |journal=Horm. Res. |volume=55 |issue= 6 |pages= 305-8 |year= 2002 |pmid= 11805436 |doi= }}
* {{cite journal | vauthors = Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N | title = Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate [[co-transport]] activity and 1alpha,25-dihydroxyvitamin D3 production | journal = J. Biol. Chem. | volume = 278 | issue = 4 | pages = 2206–11 | year = 2003 | pmid = 12419819 | doi = 10.1074/jbc.M207872200}}
*{{cite journal | author=Yamashita T, Konishi M, Miyake A, ''et al.'' |title=Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway. |journal=J. Biol. Chem. |volume=277 |issue= 31 |pages= 28265-70 |year= 2002 |pmid= 12032146 |doi= 10.1074/jbc.M202527200 }}
* {{cite journal | vauthors = Bai XY, Miao D, Goltzman D, Karaplis AC | title = The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency | journal = J. Biol. Chem. | volume = 278 | issue = 11 | pages = 9843–9 | year = 2003 | pmid = 12519781 | doi = 10.1074/jbc.M210490200 }}
*{{cite journal | author=Saito H, Kusano K, Kinosaki M, ''et al.'' |title=Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production. |journal=J. Biol. Chem. |volume=278 |issue= 4 |pages= 2206-11 |year= 2003 |pmid= 12419819 |doi= 10.1074/jbc.M207872200 }}
* {{cite journal | vauthors = Larsson T, Zahradnik R, Lavigne J, Ljunggren O, Jüppner H, Jonsson KB | title = Immunohistochemical detection of FGF-23 protein in tumors that cause oncogenic osteomalacia | journal = Eur. J. Endocrinol. | volume = 148 | issue = 2 | pages = 269–76 | year = 2003 | pmid = 12590648 | doi = 10.1530/eje.0.1480269}}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Campos M, Couture C, Hirata IY, Juliano MA, Loisel TP, Crine P, Juliano L, Boileau G, Carmona AK | title = Human recombinant endopeptidase PHEX has a strict S1' specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein | journal = Biochem. J. | volume = 373 | issue = Pt 1 | pages = 271–9 | year = 2003 | pmid = 12678920 | pmc = 1223479 | doi = 10.1042/BJ20030287}}
*{{cite journal  | author=Bai XY, Miao D, Goltzman D, Karaplis AC |title=The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency. |journal=J. Biol. Chem. |volume=278 |issue= 11 |pages= 9843-9 |year= 2003 |pmid= 12519781 |doi= 10.1074/jbc.M210490200 }}
*{{cite journal | author=Larsson T, Zahradnik R, Lavigne J, ''et al.'' |title=Immunohistochemical detection of FGF-23 protein in tumors that cause oncogenic osteomalacia. |journal=Eur. J. Endocrinol. |volume=148 |issue= 2 |pages= 269-76 |year= 2003 |pmid= 12590648 |doi= }}
*{{cite journal | author=Campos M, Couture C, Hirata IY, ''et al.'' |title=Human recombinant endopeptidase PHEX has a strict S1' specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein. |journal=Biochem. J. |volume=373 |issue= Pt 1 |pages= 271-9 |year= 2003 |pmid= 12678920 |doi= 10.1042/BJ20030287 }}
}}
{{refend}}
{{refend}}


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{{NLM content}}
{{PDB Gallery|geneid=8074}}
{{Growth factors}}
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[[Category:Growth factors]]
[[Category:Growth factors]]
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Latest revision as of 11:29, 21 September 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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View/Edit Human

Fibroblast growth factor 23 or FGF23 is a protein that in humans is encoded by the FGF23 gene.[1] FGF23 is a member of the fibroblast growth factor (FGF) family which is responsible for phosphate and vitamin D metabolism.[2][3]

Function

The main function of FGF23 seems to be regulation of phosphate concentration in plasma. FGF23 is secreted by osteocytes in response to elevated calcitriol. FGF23 acts on the kidneys, where it decreases the expression of NPT2, a sodium-phosphate cotransporter in the proximal tubule.[4] Thus, FGF23 decreases the reabsorption and increases excretion of phosphate. FGF23 may also suppress 1-alpha-hydroxylase, reducing its ability to activate vitamin D and subsequently impairing calcium absorption.[3][5]

Clinical significance

FGF23 is located on chromosome 12 and is composed of three exons. Mutations in FGF23 that render the protein resistant to proteolytic cleavage leads to increased activity of FGF23 and the renal phosphate loss found in the human disease autosomal dominant hypophosphatemic rickets. FGF23 is also overproduced by some types of tumors, such as the benign mesenchymal neoplasm Phosphaturic mesenchymal tumor causing tumor-induced osteomalacia, a paraneoplastic syndrome.[6]

Loss of FGF23 activity is thought to lead to increased phosphate levels and the clinical syndrome of familial tumor calcinosis. This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets.[7]

History

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.[8] 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

  1. ↑ 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". Biochem. Biophys. Res. Commun. 277 (2): 494–8. doi:10.1006/bbrc.2000.3696. PMID 11032749.
  2. ↑ Fukumoto S (2008). "Physiological regulation and disorders of phosphate metabolism--pivotal role of fibroblast growth factor 23". Intern. Med. 47 (5): 337–43. doi:10.2169/internalmedicine.47.0730. PMID 18310961.
  3. ↑ 3.0 3.1 Perwad F (2007). "Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro". Am J Physiol Renal Physiol. 293 (5): F1577–83. doi:10.1152/ajprenal.00463.2006. PMID 17699549.
  4. ↑ Jüppner H (2011). "Phosphate and FGF-23". Kidney Int. Suppl. 79 (121): S24–7. doi:10.1038/ki.2011.27. PMC 3257051. PMID 21346724.
  5. ↑ Rodríguez-Ortiz ME, Rodríguez M (2015). "FGF23 as a calciotropic hormone". F1000Research. 4: 1472. doi:10.12688/f1000research.7189.1. PMC 4815615. PMID 27081473.
  6. ↑ Zadik Y, Nitzan DW (October 2011). "Tumor induced osteomalacia: A forgotten paraneoplastic syndrome?". Oral Oncol. 48 (2): e9–10. doi:10.1016/j.oraloncology.2011.09.011. PMID 21985764.
  7. ↑ "Entrez Gene: FGF23 fibroblast growth factor 23".
  8. ↑ Strewler, GJ (22 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): 5945–6. doi:10.1073/pnas.11154898. PMC 33399. PMID 11371627.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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