Fibroblast growth factor 10 is aprotein that in humans is encoded by theFGF10gene.[5][6] It is a polypeptide of 208 amino acids.[7] Human FGF10 gene is highly homologous (95.6%) to rat FGF10, where it was first discovered.[8]
The protein encoded by this gene is a member of thefibroblast growth factor (FGF) family. FGF family members possess broadmitogenic 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 its involved in the branching of morphogenesis in multiple organs such as the lungs, skin, ear and salivary glands. During the limb development Tbx4/Tbx5 stimulate the production of FGF10 in thelateral plate mesoderm where it will create an epithelial-mesenchymal FGF signal with FGF8. This positive feedback loop will increase the amount ofmesenchyme resulting in a bulge. Afterwards, FGF10 will induce the formation ofapical ectodermal ridge (AER) where the foot 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 forfibroblasts, which is similar to the biological activity ofFGF7.[6]
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.[9] Although this gene is also implicated to be a primary factor in the process of wound healing.[6] 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.[10] FGF10 haploinsufficiency have been shown to increased risk of chronic‐obstructive pulmonary disease (COPD). Individuals with haploinsufficiency for FGF10 have significantly reduced Tiffeneau index, resembling chronic restrictive and obstructive pulmonary disease.[11]
FGF10knockout 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.[12] 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.[13] Mice deficient for FGF10 fail to develop normal mammary glands.[14] Guinea Pig model has shown that 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.[15]
^Klar J, Blomstrand P, Brunmark C, Badhai J, Håkansson HF, Brange CS, et al. (October 2011). "Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease".Journal of Medical Genetics.48 (10):705–709.doi:10.1136/jmedgenet-2011-100166.PMID21742743.
^Itoh N, Ohta H (May 2014). "Fgf10: a paracrine-signaling molecule in development, disease, and regenerative medicine".Current Molecular Medicine.14 (4):504–509.doi:10.2174/1566524014666140414204829.PMID24730525.
^Mailleux AA, Spencer-Dene B, Dillon C, Ndiaye D, Savona-Baron C, Itoh N, et al. (January 2002). "Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo".Development.129 (1):53–60.doi:10.1242/dev.129.1.53.PMID11782400.
^Izvolsky KI, Shoykhet D, Yang Y, Yu Q, Nugent MA, Cardoso WV (June 2003). "Heparan sulfate-FGF10 interactions during lung morphogenesis".Developmental Biology.258 (1):185–200.doi:10.1016/S0012-1606(03)00114-3.PMID12781692.
Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, et al. (January 1999). "Fgf10 is essential for limb and lung formation".Nature Genetics.21 (1):138–141.doi:10.1038/5096.PMID9916808.S2CID7296564.
Jimenez PA, Rampy MA (February 1999). "Keratinocyte growth factor-2 accelerates wound healing in incisional wounds".The Journal of Surgical Research.81 (2):238–242.doi:10.1006/jsre.1998.5501.PMID9927546.
Izvolsky KI, Zhong L, Wei L, Yu Q, Nugent MA, Cardoso WV (October 2003). "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.doi:10.1152/ajplung.00081.2003.PMID12818887.S2CID23937684.
Upadhyay D, Bundesmann M, Panduri V, Correa-Meyer E, Kamp DW (July 2004). "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.doi:10.1165/rcmb.2003-0064OC.PMID14975937.
Theodorou V, Boer M, Weigelt B, Jonkers J, van der Valk M, Hilkens J (August 2004). "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.doi:10.1038/sj.onc.1207816.PMID15208658.S2CID19488696.
Entesarian M, Matsson H, Klar J, Bergendal B, Olson L, Arakaki R, et al. (February 2005). "Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands".Nature Genetics.37 (2):125–127.doi:10.1038/ng1507.PMID15654336.S2CID36863833.
Kovacs D, Falchi M, Cardinali G, Raffa S, Carducci M, Cota C, et al. (February 2005). "Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis".Experimental Dermatology.14 (2):130–137.doi:10.1111/j.0906-6705.2005.00261.x.PMID15679583.S2CID36797243.
Beer HD, Bittner M, Niklaus G, Munding C, Max N, Goppelt A, et al. (August 2005). "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.doi:10.1038/sj.onc.1208560.PMID15806171.S2CID75364.
