Agonism of Gpr40 Protects the Capacities of Epidermal Stem Cells (ESCs) Against Ultraviolet-B (UV-B)
| Autor: | Jing Sun, Cheng-kuan Sun, Xiang-lan Li, Yulin Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmacology endocrine system Cell type Chemistry Wnt signaling pathway Pharmaceutical Science Proinflammatory cytokine Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Free fatty acid receptor 1 embryonic structures Drug Discovery Free fatty acid receptor Signal transduction Stem cell Receptor |
| Zdroj: | Drug Design, Development and Therapy. 14:5143-5153 |
| ISSN: | 1177-8881 |
| DOI: | 10.2147/dddt.s252060 |
| Popis: | Introduction Skin damage due to overexposure to ultraviolet B (UV-B) radiation can lead to the development of cancers and reduce the skin's functionality as a vital protective barrier. Epidermal stem cells (ESCs) are pluripotent cells responsible for skin regeneration and healing. Upon exposure to UV-B radiation, ESCs produce excess amounts of reactive oxygen species (ROS) and inflammatory cytokines. However, the functional protection of ESCs is not fully explored. G-protein coupled G protein-coupled receptor 40 (Gpr40) is a free fatty acid receptor that is emerging as a potential treatment target for various diseases. Gpr40 has been found to be expressed in various cell types. Methods ESCs were exposed to UV-B at the intensities of 25, 50, and 100 mJ/cm2 for 24 h using TL 20 W/12 RS UV lamps. ESCs were treated with UV-B at 50 mJ/cm2 in the presence or absence of 25 or 50 µM of the Gpr40 agonist GW9508 for 24 h. The gene expression of the Wnt1 pathway and proinflammatory cytokines were evaluated. To antagonize Gpr40 expression, ESCs were treated with 10 µM GW1100. Results Our findings demonstrate that Gpr40 agonism can reduce the production of ROS as well as the expression of interleukins 1β and 8, two key proinflammatory cytokines. We demonstrate that agonism of Gpr40 can rescue the reduction in integrin β1 and Krt19 induced by UV-B exposure, thereby improving the capacities of ESCs to resist UV-B damage. Moreover, we show that the effects of Gpr40 agonism observed in our experiments are mediated through the Wnt/β-catenin canonical signaling pathway, as evidenced by the expression of Wnt1 and cyclin D1. Conclusion Our findings present evidence of the role of Gpr40 agonism in mediating the protective capacities of ESCs against insult from UV-B radiation. |
| Databáze: | OpenAIRE |
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