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 β 1 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.

Keywords: Gpr40, G protein-coupled receptors, ultraviolet-B radiation, epidermal stem cells, Wnt, GW9508


中文翻译：

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Gpr40 的激动作用可保护表皮干细胞 (ESC) 对抗紫外线 B (UV-B) 的能力

简介：由于过度暴露于紫外线 B (UV-B) 辐射造成的皮肤损伤会导致癌症的发展，并降低皮肤作为重要保护屏障的功能。表皮干细胞 (ESC) 是负责皮肤再生和愈合的多能细胞。暴露于 UV-B 辐射后，ESC 会产生过量的活性氧 (ROS) 和炎性细胞因子。然而，胚胎干细胞的功能保护尚未得到充分探索。G 蛋白偶联 G 蛋白偶联受体 40 (Gpr40) 是一种游离脂肪酸受体，正在成为各种疾病的潜在治疗靶点。已发现 Gpr40 在各种细胞类型中表达。
方法：将 ESC 暴露于 25、50 和 100 mJ/cm ^{2强度的 UV-B}使用 TL 20 W/12 RS 紫外灯 24 小时。在存在或不存在 25 或 50 μM Gpr40 激动剂 GW9508 的情况下，用 50 mJ/cm ^{2的 UV-B 处理 ESC 24 小时。}评估了 Wnt1 通路和促炎细胞因子的基因表达。为了拮抗 Gpr40 的表达，用 10 μM GW1100 处理 ESC。
结果：我们的研究结果表明，Gpr40 激动剂可以减少 ROS 的产生以及白细胞介素 1β 和 8（两种关键的促炎细胞因子）的表达。我们证明 Gpr40 的激动可以挽救整合素 β 1和Krt19的减少由 UV-B 暴露诱导，从而提高 ESC 抵抗 UV-B 损伤的能力。此外，我们表明在我们的实验中观察到的 Gpr40 激动作用是通过 Wnt/β-连环蛋白经典信号通路介导的，如 Wnt1 和细胞周期蛋白 D1 的表达所证明的。
结论：我们的研究结果提供了 Gpr40 激动剂在介导 ESC 对 UV-B 辐射损伤的保护能力中的作用的证据。

关键词： Gpr40，G蛋白偶联受体，紫外线-B辐射，表皮干细胞，Wnt，GW9508