Fgf5, a member of the fibroblast growth factor family, functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase, mediating the transition from the anagen growth phase to the catagen regression phase. It also interacts with various signaling pathways, such as the Hedgehog (Hh) signaling pathway in the developing prostate [1].

Spontaneous and engineered FGF5 mutations in mammalian animal models result in long hair phenotypes, and in humans, inherited FGF5 mutations lead to trichomegaly (long eyelashes). Functional studies in other cancer models suggest FGF5 overexpression is an oncogenic driver. For example, in osteosarcoma, FGF5 is overexpressed and promotes cell proliferation by activating the MAPK signaling pathway. In nasopharyngeal carcinoma, cancer-associated fibroblasts secrete FGF5 to inhibit ferroptosis and decrease cisplatin sensitivity [1,4,5,6].

In addition, FGF5 has protective effects in some injury models. In endothelial cells exposed to lipopolysaccharide (LPS), FGF5 alleviates acute lung injury via the AKT signal pathway. It also protects the heart from sepsis injury by attenuating cardiomyocyte pyroptosis through inhibiting CaMKII/NFκB signaling [3,7].

In conclusion, Fgf5 is a crucial regulator in multiple biological processes, especially in the hair cycle. Its role in various diseases, such as cancer and injury-related conditions, has been revealed through functional studies in different models. Understanding Fgf5 may provide new therapeutic strategies for these diseases.

References:

1. Carrion, Evelyn A, Moses, Malcolm M, Behringer, Richard R. 2023. FGF5. In Differentiation; research in biological diversity, 139, 100736. doi:10.1016/j.diff.2023.10.004. https://pubmed.ncbi.nlm.nih.gov/37957094/

2. Stangis, Mary M, Colah, Avan N, McLean, Dalton T, Collier, Lara S, Ricke, William A. 2023. Potential roles of FGF5 as a candidate therapeutic target in prostate cancer. In American journal of clinical and experimental urology, 11, 452-466. doi:. https://pubmed.ncbi.nlm.nih.gov/38148937/

3. Li, Yuhua, Cui, Shengyu, Wu, Bing, Zhang, Furong, Xia, Hao. 2022. FGF5 alleviated acute lung injury via AKT signal pathway in endothelial cells. In Biochemical and biophysical research communications, 634, 152-158. doi:10.1016/j.bbrc.2022.09.112. https://pubmed.ncbi.nlm.nih.gov/36244113/

4. Amano, Ryo, Namekata, Masato, Horiuchi, Masataka, Yamamoto, Masakuni, Sakamoto, Taiichi. 2021. Specific inhibition of FGF5-induced cell proliferation by RNA aptamers. In Scientific reports, 11, 2976. doi:10.1038/s41598-021-82350-w. https://pubmed.ncbi.nlm.nih.gov/33536494/

5. Liu, Feng, Tang, Ling, Liu, Huai, Wang, Hui, Chen, Pan. 2024. Cancer-associated fibroblasts secrete FGF5 to inhibit ferroptosis to decrease cisplatin sensitivity in nasopharyngeal carcinoma through binding to FGFR2. In Cell death & disease, 15, 279. doi:10.1038/s41419-024-06671-0. https://pubmed.ncbi.nlm.nih.gov/38637504/

6. Han, Dunxin, Wang, Mingming, Yu, Zhongkai, Ren, Zhongwu, Yin, Jun. 2019. FGF5 promotes osteosarcoma cells proliferation via activating MAPK signaling pathway. In Cancer management and research, 11, 6457-6466. doi:10.2147/CMAR.S200234. https://pubmed.ncbi.nlm.nih.gov/31372048/

7. Cui, Shengyu, Li, Yuhua, Zhang, Xutao, Xia, Hao, Xu, Lin. 2022. FGF5 protects heart from sepsis injury by attenuating cardiomyocyte pyroptosis through inhibiting CaMKII/NFκB signaling. In Biochemical and biophysical research communications, 636, 104-112. doi:10.1016/j.bbrc.2022.10.080. https://pubmed.ncbi.nlm.nih.gov/36368152/