Fibroblast growth factor 18 (FGF-18) is aprotein that is encoded by theFGF18gene in humans.[5][6][7] The protein was first discovered in 1998, when two newly-identified murine genes Fgf17 and Fgf18 were described and confirmed as being closely related by sequence homology to Fgf8.[8] The three proteins were eventually grouped into theFGF8 subfamily, which contains several of the endocrine FGF superfamily members FGF8, FGF17, and FGF18.[9] Subsequent studies identified FGF18's role in promoting chondrogenesis,[10] and an apparent specific activity for the generation of the hyaline cartilage in articular joints.[11]
Theprotein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, includingembryonic development, cell growth,morphogenesis, and tissue repair. It has been shownin vitro that this protein is able to induce the outgrowth ofneurites inPC12 cells.[5]
FGF18 signals throughfibroblast growth factor receptor (FGFR) family, preferentially binding FGFR 3c (followed by 4△, 2c, 1c, and finally 3b),[12] signaling via FGFR3 promotes generation of cartilage (chondrogenesis).[13] FGF18 and has been shown to cause thickening of cartilage in amurine model ofosteoarthritis,[14] and the recombinant version of it (sprifermin) is in a clinical trial as a potential treatment forosteoarthritis (OA).[15] Recent findings from a placebo-controlled randomized clinical study demonstrate the potential of FGF18 to reduce the rate of progression tojoint replacement surgery[16] and delay progression of OA-related pain (WOMAC).[17] Another study suggested the ability of FGF18 to inhibit intravertebral disc degeneration in a rabbit model of the disease.
Studies of the similar proteins inmouse andchick suggested that this protein is apleiotropic growth factor that stimulates proliferation in a number of tissues, most notably theliver andsmall intestine. Knockout studies of the similar gene in mice implied the role of this protein in regulating proliferation and differentiation of midline cerebellar structures.[7]
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.[18] The role of FGF18 in the heart appears to be associated with protection from stress-induced pathologicalcardiac hypertrophy via the induction of survival or regenerative signals.[19] Similarly, studies confirmed that overexpression of FGF18 in the liver was able to attenuateliver fibrosis following chemically-induced injury.[20]
Studies of FGF18 in relation to oncology have shown both decreased levels[21] and increased levels[22] of FGF18 in a number of cancer types and stages, however, FGF18 does not appear to be causative or prognostic[23] and long-term clinical studies of the FGF18 analog, sprifermin, have demonstrated an excellent safety profile with no reported oncogenic effects.[16]
^Tong G, Chen X, Lee J, Fan J, Li S, Zhu K, et al. (April 2022). "Fibroblast growth factor 18 attenuates liver fibrosis and HSCs activation via the SMO-LATS1-YAP pathway".Pharmacological Research.178 106139.doi:10.1016/j.phrs.2022.106139.ISSN1096-1186.PMID35202822.S2CID247030847.
Haque T, Nakada S, Hamdy RC (2007). "A review of FGF18: Its expression, signaling pathways and possible functions during embryogenesis and post-natal development".Histology and Histopathology.22 (1):97–105.doi:10.14670/HH-22.97.PMID17128416.
Hu MC, Wang YP, Qiu WR (1999). "Human fibroblast growth factor-18 stimulates fibroblast cell proliferation and is mapped to chromosome 14p11".Oncogene.18 (16):2635–2642.doi:10.1038/sj.onc.1202616.PMID10353607.S2CID32973576.
Xu J, Liu Z, Ornitz DM (2000). "Temporal and spatial gradients of Fgf8 and Fgf17 regulate proliferation and differentiation of midline cerebellar structures".Development.127 (9). Cambridge, England:1833–1843.doi:10.1242/dev.127.9.1833.PMID10751172.
Whitmore TE, Maurer MF, Sexson S, Raymond F, Conklin D, Deisher TA (2001). "Assignment of fibroblast growth factor 18 (FGF18) to human chromosome 5q34 by use of radiation hybrid mapping and fluorescence in situ hybridization".Cytogenetics and Cell Genetics.90 (3–4):231–233.doi:10.1159/000056775.PMID11124520.S2CID84820296.
Cormier S, Leroy C, Delezoide AL, Silve C (2005). "Expression of fibroblast growth factors 18 and 23 during human embryonic and fetal development".Gene Expression Patterns.5 (4):569–573.doi:10.1016/j.modgep.2004.10.008.PMID15749088.
Antoine M, Wirz W, Tag CG, Mavituna M, Emans N, Korff T, et al. (2005). "Expression pattern of fibroblast growth factors (FGFs), their receptors and antagonists in primary endothelial cells and vascular smooth muscle cells".Growth Factors.23 (2). Chur, Switzerland:87–95.doi:10.1080/08977190500096004.PMID16019430.S2CID27380246.
Antoine M, Wirz W, Tag CG, Gressner AM, Wycislo M, Muller R, et al. (2006). "Fibroblast growth factor 16 and 18 are expressed in human cardiovascular tissues and induce on endothelial cells migration but not proliferation".Biochemical and Biophysical Research Communications.346 (1):224–233.doi:10.1016/j.bbrc.2006.05.105.PMID16756958.
