FGF10 explained

Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10 gene.^{[1] [2]} It is a polypeptide of 208 amino acids.^[3] Human FGF10 gene is highly homologous (95.6%) to rat FGF10, where it was first discovered.^[4]

Function

The protein 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, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. Fibroblast growth factor 10 is a paracrine signaling molecule seen first in the limb bud and organogenesis development. FGF10 starts the developing of limbs and is involved in the branching of morphogenesis in multiple organs such as the lungs, skin, ear and salivary glands. During limb development Tbx4/Tbx5 stimulate the production of FGF10 in the lateral plate mesoderm where it will create an epithelial-mesenchymal FGF signal with FGF8. This positive feedback loop will increase the amount of mesenchyme resulting in a bulge. Afterwards, FGF10 will induce the formation of apical ectodermal ridge (AER) where the feet and hands will be formed. Lung development uses the same epithelial-mesenchymal signaling from FGF10 in the foregut mesenchyme with FGFR2 in the foregut epithelium. FGF10 signaling is required for epithelial branching. Therefore, all branching morphogen organs such as the lungs, skin, ear and salivary glands required the constant expression of FGF10. This protein exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7.^[2]

Clinical significance

Nonsense mutations may also occur with the absence of FGF10 such as LADD and ALSG syndrome. Nevertheless, complications may arise from FGF10 signaling such as pancreatic and breast cancer. Moreover, studies have identified variants near the FGF10 locus as a genetic risk factor for breast cancer susceptibility.^[5] Although this gene is also implicated to be a primary factor in the process of wound healing.^[2] Heterozygous FGF10 variants and childhood intestinal lung disease (child) linked to potential early lethal outcomes. Also, FGF10 variants have been associated with abnormal epithelial repair.^[6] FGF10 haploinsufficiency has been shown to increase the risk of chronic‐obstructive pulmonary disease (COPD). Individuals with haploinsufficiency for FGF10 have significantly reduced Tiffeneau index, resembling chronic restrictive and obstructive pulmonary disease.^[7]

Animal studies

FGF10 knockout mice die right after birth. The mice showed no developing organs such as lungs, salivary glands, kidney or definitive limbs once autopsied. Studies of the mouse homolog suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of limb bud formation.^[8] FGF knockout mice also have impaired epicardial cell expansion following neonatal heart injury, as well as reduced expression of epicardial markers Wt1 and Tbx18, and mesenchymal markers such as Snai1, Twist1, and Postn.^[9] Mice deficient in FGF10 fail to develop normal mammary glands.^[10] Guinea Pig model has shown that the FGF10 monoclonal antibody can decrease the number of inflammatory cells in the dermis and its inhibitory effect on inflammatory cells is like that of hydrocortisone butyrate.^[11]

Interactions

FGF10 has been shown to interact with Heparan sulfate ^[12] and Toll-like receptors.^[13]

See also

• Turtle shell

Further reading

• Igarashi M, Finch PW, Aaronson SA . Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7) . The Journal of Biological Chemistry . 273 . 21 . 13230–13235 . May 1998 . 9582367 . 10.1074/jbc.273.21.13230 . free . Stuart A. Aaronson .
• Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S . Fgf10 is essential for limb and lung formation . Nature Genetics . 21 . 1 . 138–141 . January 1999 . 9916808 . 10.1038/5096 . 7296564 .
• Jimenez PA, Rampy MA . Keratinocyte growth factor-2 accelerates wound healing in incisional wounds . The Journal of Surgical Research . 81 . 2 . 238–242 . February 1999 . 9927546 . 10.1006/jsre.1998.5501 .
• Ropiquet F, Giri D, Kwabi-Addo B, Schmidt K, Ittmann M . FGF-10 is expressed at low levels in the human prostate . The Prostate . 44 . 4 . 334–338 . September 2000 . 10951499 . 10.1002/1097-0045(20000901)44:4<334::AID-PROS11>3.0.CO;2-G . 35828553 .
• Marchese C, Felici A, Visco V, Lucania G, Igarashi M, Picardo M, Frati L, Torrisi MR . Fibroblast growth factor 10 induces proliferation and differentiation of human primary cultured keratinocytes . The Journal of Investigative Dermatology . 116 . 4 . 623–628 . April 2001 . 11286634 . 10.1046/j.0022-202x.2001.01280.x . free .
• Bagai S, Rubio E, Cheng JF, Sweet R, Thomas R, Fuchs E, Grady R, Mitchell M, Bassuk JA . Fibroblast growth factor-10 is a mitogen for urothelial cells . The Journal of Biological Chemistry . 277 . 26 . 23828–23837 . June 2002 . 11923311 . 10.1074/jbc.M201658200 . free .
• Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M . Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors . Proceedings of the National Academy of Sciences of the United States of America . 100 . 5 . 2266–2271 . March 2003 . 12591959 . 151329 . 10.1073/pnas.0436500100 . free . 2003PNAS..100.2266Y .
• Upadhyay D, Lecuona E, Comellas A, Kamp DW, Sznajder JI . Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway . FEBS Letters . 545 . 2–3 . 173–176 . June 2003 . 12804770 . 10.1016/S0014-5793(03)00527-1 . 40221645 . free . 2003FEBSL.545..173U .
• Izvolsky KI, Zhong L, Wei L, Yu Q, Nugent MA, Cardoso WV . Heparan sulfates expressed in the distal lung are required for Fgf10 binding to the epithelium and for airway branching . American Journal of Physiology. Lung Cellular and Molecular Physiology . 285 . 4 . L838–L846 . October 2003 . 12818887 . 10.1152/ajplung.00081.2003 . 23937684 .
• Tomlinson DC, Grindley JC, Thomson AA . Regulation of Fgf10 gene expression in the prostate: identification of transforming growth factor-beta1 and promoter elements . Endocrinology . 145 . 4 . 1988–1995 . April 2004 . 14726452 . 10.1210/en.2003-0842 . free .
• Upadhyay D, Bundesmann M, Panduri V, Correa-Meyer E, Kamp DW . Fibroblast growth factor-10 attenuates H2O2-induced alveolar epithelial cell DNA damage: role of MAPK activation and DNA repair . American Journal of Respiratory Cell and Molecular Biology . 31 . 1 . 107–113 . July 2004 . 14975937 . 10.1165/rcmb.2003-0064OC .
• Theodorou V, Boer M, Weigelt B, Jonkers J, van der Valk M, Hilkens J . Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas . Oncogene . 23 . 36 . 6047–6055 . August 2004 . 15208658 . 10.1038/sj.onc.1207816 . 19488696 .
• Ibrahimi OA, Yeh BK, Eliseenkova AV, Zhang F, Olsen SK, Igarashi M, Aaronson SA, Linhardt RJ, Mohammadi M . Analysis of mutations in fibroblast growth factor (FGF) and a pathogenic mutation in FGF receptor (FGFR) provides direct evidence for the symmetric two-end model for FGFR dimerization . Molecular and Cellular Biology . 25 . 2 . 671–684 . January 2005 . 15632068 . 543411 . 10.1128/MCB.25.2.671-684.2005 .
• Entesarian M, Matsson H, Klar J, Bergendal B, Olson L, Arakaki R, Hayashi Y, Ohuchi H, Falahat B, Bolstad AI, Jonsson R, Wahren-Herlenius M, Dahl N . Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands . Nature Genetics . 37 . 2 . 125–127 . February 2005 . 15654336 . 10.1038/ng1507 . 36863833 .
• Kovacs D, Falchi M, Cardinali G, Raffa S, Carducci M, Cota C, Amantea A, Torrisi MR, Picardo M . Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis . Experimental Dermatology . 14 . 2 . 130–137 . February 2005 . 15679583 . 10.1111/j.0906-6705.2005.00261.x . 36797243 .
• Ye F, Duvillié B, Scharfmann R . Fibroblast growth factors 7 and 10 are expressed in the human embryonic pancreatic mesenchyme and promote the proliferation of embryonic pancreatic epithelial cells . Diabetologia . 48 . 2 . 277–281 . February 2005 . 15690149 . 10.1007/s00125-004-1638-6 . free .
• Beer HD, Bittner M, Niklaus G, Munding C, Max N, Goppelt A, Werner S . The fibroblast growth factor binding protein is a novel interaction partner of FGF-7, FGF-10 and FGF-22 and regulates FGF activity: implications for epithelial repair . Oncogene . 24 . 34 . 5269–5277 . August 2005 . 15806171 . 10.1038/sj.onc.1208560 . 75364 .

External links

• OMIM entry on aplasia of lacrimal and salivary glands

Notes and References

1. Emoto H, Tagashira S, Mattei MG, Yamasaki M, Hashimoto G, Katsumata T, Negoro T, Nakatsuka M, Birnbaum D, Coulier F, Itoh N . Structure and expression of human fibroblast growth factor-10 . The Journal of Biological Chemistry . 272 . 37 . 23191–23194 . September 1997 . 9287324 . 10.1074/jbc.272.37.23191 . free .
2. Web site: Entrez Gene: FGF10 fibroblast growth factor 10.
3. Emoto H, Tagashira S, Mattei MG, Yamasaki M, Hashimoto G, Katsumata T, Negoro T, Nakatsuka M, Birnbaum D, Coulier F, Itoh N . Structure and expression of human fibroblast growth factor-10 . English . The Journal of Biological Chemistry . 272 . 37 . 23191–23194 . September 1997 . 9287324 . 10.1074/jbc.272.37.23191 . free .
4. Lü J, Izvolsky KI, Qian J, Cardoso WV . Identification of FGF10 targets in the embryonic lung epithelium during bud morphogenesis . The Journal of Biological Chemistry . 280 . 6 . 4834–4841 . February 2005 . 15556938 . 10.1074/jbc.M410714200 . free .
5. Rivetti S, Chen C, Chen C, Bellusci S . Fgf10/Fgfr2b Signaling in Mammary Gland Development, Homeostasis, and Cancer . English . Frontiers in Cell and Developmental Biology . 8 . 415 . 2020-06-26 . 32676501 . 7333592 . 10.3389/fcell.2020.00415 . free .
6. Schütz K, Schmidt A, Schwerk N, Renz DM, Gerard B, Schaefer E, Antal MC, Peters S, Griese M, Rapp CK, Engels H, Cremer K, Bergmann AK, Schmidt G, Auber B, Kamp JC, Laenger F, von Hardenberg S . Variants in FGF10 cause early onset of severe childhood interstitial lung disease: A detailed description of four affected children . Pediatric Pulmonology . 58 . 11 . 3095–3105 . November 2023 . 37560881 . 10.1002/ppul.26627 . free .
7. Klar J, Blomstrand P, Brunmark C, Badhai J, Håkansson HF, Brange CS, Bergendal B, Dahl N . Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease . Journal of Medical Genetics . 48 . 10 . 705–709 . October 2011 . 21742743 . 10.1136/jmedgenet-2011-100166 .
8. Itoh N, Ohta H . Fgf10: a paracrine-signaling molecule in development, disease, and regenerative medicine . Current Molecular Medicine . 14 . 4 . 504–509 . May 2014 . 24730525 . 10.2174/1566524014666140414204829 .
9. Clayton NS, Grose RP . Emerging Roles of Fibroblast Growth Factor 10 in Cancer . Frontiers in Genetics . 9 . 499 . 2018-10-24 . 30405704 . 6207577 . 10.3389/fgene.2018.00499 . free .
10. Mailleux AA, Spencer-Dene B, Dillon C, Ndiaye D, Savona-Baron C, Itoh N, Kato S, Dickson C, Thiery JP, Bellusci S . Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo . Development . 129 . 1 . 53–60 . January 2002 . 11782400 . 10.1242/dev.129.1.53 .
11. Xia JX, Mei XL, Zhu WJ, Li X, Jin XH, Mou Y, Yu K, Wang YY, Li FQ . Effect of FGF10 monoclonal antibody on psoriasis-like model in guinea pigs . International Journal of Clinical and Experimental Pathology . 7 . 5 . 2219–2228 . 2014 . 24966930 . 4069920 .
12. Izvolsky KI, Shoykhet D, Yang Y, Yu Q, Nugent MA, Cardoso WV . Heparan sulfate-FGF10 interactions during lung morphogenesis . Developmental Biology . 258 . 1 . 185–200 . June 2003 . 12781692 . 10.1016/S0012-1606(03)00114-3 .
13. Liu L, Song C, Li J, Wang Q, Zhu M, Hu Y, Chen J, Chen C, Zhang JS, Dong N, Chen C . Fibroblast growth factor 10 alleviates particulate matter-induced lung injury by inhibiting the HMGB1-TLR4 pathway . Aging . 12 . 2 . 1186–1200 . January 2020 . 31958320 . 7053597 . 10.18632/aging.102676 .