Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10gene.[5][6]
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 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 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 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 for fibroblasts, which is similar to the biological activity of FGF7.[6]
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. Although this gene is also implicated to be a primary factor in the process of wound healing.[6]
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.[7]
^Itoh N, Ohta H (2014). "Fgf10: a paracrine-signaling molecule in development, disease, and regenerative medicine". Current Molecular Medicine. 14 (4): 504–9. doi:10.2174/1566524014666140414204829. PMID24730525.
Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S (January 1999). "Fgf10 is essential for limb and lung formation". Nature Genetics. 21 (1): 138–41. 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): 238–42. 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): L838-46. 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): 107–13. 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): 6047–55. doi:10.1038/sj.onc.1207816. PMID15208658. S2CID19488696.
Beer HD, Bittner M, Niklaus G, Munding C, Max N, Goppelt A, Werner S (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): 5269–77. doi:10.1038/sj.onc.1208560. PMID15806171. S2CID75364.
