Crosstalk between androgen and Wnt/β-catenin leads to changes of wool density in FGF5-knockout sheep
| Autor: | Xue-Ling Xu, Jie Zhang, Yan Li, Yao Li, Yue Zhao, Rui Zhang, Xiaosheng Zhang, Guoshi Liu, Shou-Long Deng, Zhengxing Lian, Kun Jia |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Fibroblast Growth Factor 5 medicine.drug_class Immunology Models Biological Article Gene Knockout Techniques 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Fibroblast growth factor-5 Hair cycle GLI2 medicine Animals Hedgehog Proteins lcsh:QH573-671 beta Catenin Gene Editing Sheep Base Sequence biology lcsh:Cytology Wool Fibroblast growth factor receptor 1 Finasteride Wnt signaling pathway Dihydrotestosterone Dermis Cell Biology Androgen Cell biology Wnt Proteins 030104 developmental biology 030220 oncology & carcinogenesis Catenin Genetic engineering Androgens Extracellular signalling molecules biology.gene Hair Follicle Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 11, Iss 5, Pp 1-12 (2020) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-2622-x |
| Popis: | Fibroblast growth factor 5 (FGF5) is a famous dominant inhibitor of anagen phase of hair cycle. Mutations of FGF5 gene result in a longer wool in mice, donkeys, dogs, cats, and even in human eyelashes. Sheep is an important source of wool production. How to improve the production of wool quickly and effectively is an urgent problem to be solved. In this study, we generated five FGF5-knockout Dorper sheep by the CRISPR/Cas9 system. The expression level of FGF5 mRNA in knockout (KO) sheep decreased significantly, and all FGF5 proteins were dysfunctional. The KO sheep displayed a significant increase in fine-wool and active hair-follicle density. The crosstalk between androgen and Wnt/β-catenin signaling downstream of FGF5 gene plays a key role. We established downstream signaling cascades for the first time, including FGF5, FGFR1, androgen, AR, Wnt/β-catenin, Shh/Gli2, c-MYC, and KRTs. These findings further improved the function of FGF5 gene, and provided therapeutic ideas for androgen alopecia. |
| Databáze: | OpenAIRE |
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