Fibroblast growth factor 18

FGF18 signals through fibroblast growth factor receptor (FGFR) family, preferentially binding FGFR 3c (followed by 4△, 2c, 1c, and finally 3b),{{Cite journal | vauthors = Ornitz DM, Itoh N | title = The Fibroblast Growth Factor signaling pathway | journal = Wiley Interdisciplinary Reviews. Developmental Biology | volume = 4 | issue = 3 | pages = 215–266 | date = 2015 | pmid = 25772309 | pmc = 4393358 | doi = 10.1002/wdev.176 | issn = 1759-7692 }} signaling via FGFR3 promotes generation of cartilage (chondrogenesis).{{Cite journal | vauthors = Davidson D, Blanc A, Filion D, Wang H, Plut P, Pfeffer G, Buschmann MD, Henderson JE | title = Fibroblast Growth Factor (FGF) 18 Signals through FGF Receptor 3 to Promote Chondrogenesis | journal = The Journal of Biological Chemistry | volume = 280 | issue = 21 | pages = 20509–20515 | year = 2005 | pmid = 15781473 | doi = 10.1074/jbc.M410148200 | doi-access = free }} FGF18 and has been shown to cause thickening of cartilage in a murine model of osteoarthritis,{{Cite journal | vauthors = Moore EE, Bendele AM, Thompson DL, Littau A, Waggie KS, Reardon B, Ellsworth JL | title = Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis | journal = Osteoarthritis and Cartilage | volume = 13 | issue = 7 | pages = 623–631 | year = 2005 | pmid = 15896984 | doi = 10.1016/j.joca.2005.03.003 | doi-access = free }} and the recombinant version of it (sprifermin) is in a clinical trial as a potential treatment for osteoarthritis (OA).{{citation|url=http://www.merckgroup.com/en/media/extNewsDetail.html?newsId=502569FC1F1AFE50C1257B2F00538E80&newsType=1|access-date=2013-04-02|title=Merck Announces Collaboration With Nordic Bioscience for Sprifermin in Osteoarthritis of the Knee}} Recent findings from a placebo-controlled randomized clinical study demonstrate the potential of FGF18 to reduce the rate of progression to joint replacement surgery{{Cite journal | vauthors = Eckstein F, Hochberg MC, Guehring H, Moreau F, Ona V, Bihlet AR, Byrjalsen I, Andersen JR, Daelken B, Guenther O, Ladel C, Michaelis M, Conaghan PG | title = Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study | journal = Annals of the Rheumatic Diseases | volume = 80 | issue = 8 | pages = 1062–1069 | date = August 2021 | pmid = 33962962 | pmc = 8292562 | doi = 10.1136/annrheumdis-2020-219181 | issn = 1468-2060 }} and delay progression of OA-related pain (WOMAC).{{Cite journal | vauthors = Conaghan PG, Katz N, Hunter D, Guermazi A, Hochberg M, Somberg K, Clive J, Johnson M, Goel N | title = Pos1348 Effects of Sprifermin on a Novel Outcome of Osteoarthritis Symptom Progression: Post-Hoc Analysis of the Forward Randomized Trial | journal = Annals of the Rheumatic Diseases | volume = 82 | issue = Suppl 1 | pages = 1025–1026 | date = 2023-06-01 | doi = 10.1136/annrheumdis-2023-eular.2454 | url = https://ard.bmj.com/content/82/Suppl_1/1025 | language = en | issn = 0003-4967 | doi-access = free }} Another study suggested the ability of FGF18 to inhibit intravertebral disc degeneration in a rabbit model of the disease.

Studies of the similar proteins in mouse and chick suggested that this protein is a pleiotropic growth factor that stimulates proliferation in a number of tissues, most notably the liver and small intestine. Knockout studies of the similar gene in mice implied the role of this protein in regulating proliferation and differentiation of midline cerebellar structures.

FGF18 appears to be a pleiotropic factor, expressed in a broad range of tissues and organs; the highest level of FGF18 expression were confirmed in the right ventricle interventricular septum of the heart.{{Cite web | title = Genevisible: O76093 | url = https://genevisible.com/tissues/HS/UniProt/O76093 | access-date = Jul 22, 2023 | website = Genevisible }} The role of FGF18 in the heart appears to be associated with protection from stress-induced pathological cardiac hypertrophy via the induction of survival or regenerative signals.{{Cite web | title = fgf18 heart - Search Results - PubMed | url = https://pubmed.ncbi.nlm.nih.gov/?term=fgf18+heart | access-date = 2023-07-22 | website = PubMed | language = en }} Similarly, studies confirmed that overexpression of FGF18 in the liver was able to attenuate liver fibrosis following chemically-induced injury.{{Cite journal | vauthors = Tong G, Chen X, Lee J, Fan J, Li S, Zhu K, Hu Z, Mei L, Sui Y, Dong Y, Chen R, Jin Z, Zhou B, Li X, Wang X, Cong W, Huang P, Jin L | title = Fibroblast growth factor 18 attenuates liver fibrosis and HSCs activation via the SMO-LATS1-YAP pathway | journal = Pharmacological Research | volume = 178 | pages = 106139 | date = April 2022 | pmid = 35202822 | doi = 10.1016/j.phrs.2022.106139 | issn = 1096-1186 | s2cid = 247030847 }}

Studies of FGF18 in relation to oncology have shown both decreased levels{{Cite journal | vauthors = Mosleh B, Schelch K, Mohr T, Klikovits T, Wagner C, Ratzinger L, Dong Y, Sinn K, Ries A, Berger W, Grasl-Kraupp B, Hoetzenecker K, Laszlo V, Dome B, Hegedus B, Jakopovic M, Hoda MA, Grusch M | title = Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis | journal = Thoracic Cancer | volume = 14 | issue = 22 | pages = 2177–2186 | date = 2023-06-21 | pmid = 37340889 | pmc = 10396789 | doi = 10.1111/1759-7714.15004 | issn = 1759-7714 | s2cid = 259210554 }} and increased levels{{Cite journal | vauthors = Flannery CA, Fleming AG, Choe GH, Naqvi H, Zhang M, Sharma A, Taylor HS | title = Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium | journal = Endocrinology | volume = 157 | issue = 10 | pages = 3699–3708 | date = October 2016 | pmid = 27267714 | pmc = 5045514 | doi = 10.1210/en.2016-1233 | issn = 1945-7170 }} of FGF18 in a number of cancer types and stages, however, FGF18 does not appear to be causative or prognostic{{Cite web | title = Expression of FGF18 in cancer - Summary - The Human Protein Atlas | url = https://www.proteinatlas.org/ENSG00000156427-FGF18/pathology | access-date = 2023-07-22 | website = www.proteinatlas.org }} and long-term clinical studies of the FGF18 analog, sprifermin, have demonstrated an excellent safety profile with no reported oncogenic effects.{{Cite journal | vauthors = Eckstein F, Hochberg MC, Guehring H, Moreau F, Ona V, Bihlet AR, Byrjalsen I, Andersen JR, Daelken B, Guenther O, Ladel C, Michaelis M, Conaghan PG | title = Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study | journal = Annals of the Rheumatic Diseases | volume = 80 | issue = 8 | pages = 1062–1069 | date = August 2021 | pmid = 33962962 | pmc = 8292562 | doi = 10.1136/annrheumdis-2020-219181 | issn = 1468-2060 }}

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• {{PDBe-KB2|O76093|Fibroblast growth factor 18}}

{{Growth factors}}

{{Growth factor receptor modulators}}