Agonism of Gpr40 Protects the Capacities of Epidermal Stem Cells (ESCs) Against Ultraviolet-B (UV-B)

Drug Des Devel Ther. 2020 Nov 24;14:5143-5153. doi: 10.2147/DDDT.S252060. eCollection 2020.

ABSTRACT

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.

PMID:33262575 | PMC:PMC7699447 | DOI:10.2147/DDDT.S252060