FGF10

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.

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. Although this gene is also implicated to be a primary factor in the process of wound healing. 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. 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.

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. 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. Mice deficient in FGF10 fail to develop normal mammary glands. 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.

Interactions

FGF10 has been shown to interact with Heparan sulfate and Toll-like receptors.

References

References

1. (September 1997). "Structure and expression of human fibroblast growth factor-10". The Journal of Biological Chemistry.
2. "Entrez Gene: FGF10 fibroblast growth factor 10".
3. (September 1997). "Structure and expression of human fibroblast growth factor-10". The Journal of Biological Chemistry.
4. (February 2005). "Identification of FGF10 targets in the embryonic lung epithelium during bud morphogenesis". The Journal of Biological Chemistry.
5. (2020-06-26). "Fgf10/Fgfr2b Signaling in Mammary Gland Development, Homeostasis, and Cancer". Frontiers in Cell and Developmental Biology.
6. (November 2023). "Variants in FGF10 cause early onset of severe childhood interstitial lung disease: A detailed description of four affected children". Pediatric Pulmonology.
7. (October 2011). "Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease". Journal of Medical Genetics.
8. (May 2014). "Fgf10: a paracrine-signaling molecule in development, disease, and regenerative medicine". Current Molecular Medicine.
9. (2018-10-24). "Emerging Roles of Fibroblast Growth Factor 10 in Cancer". Frontiers in Genetics.
10. (January 2002). "Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo". Development.
11. (2014). "Effect of FGF10 monoclonal antibody on psoriasis-like model in guinea pigs". International Journal of Clinical and Experimental Pathology.
12. (June 2003). "Heparan sulfate-FGF10 interactions during lung morphogenesis". Developmental Biology.
13. (January 2020). "Fibroblast growth factor 10 alleviates particulate matter-induced lung injury by inhibiting the HMGB1-TLR4 pathway". Aging.