Department of Hand Surgery, The Third Hospital of Jilin University, Changchun, Jilin 130033, People's Republic of China.
Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, Jilin 130033, People's Republic of China.
Drug Des Devel Ther. 2020 Nov 24;14:5143-5153. doi: 10.2147/DDDT.S252060. eCollection 2020.
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.
ESCs were exposed to UV-B at the intensities of 25, 50, and 100 mJ/cm for 24 h using TL 20 W/12 RS UV lamps. ESCs were treated with UV-B at 50 mJ/cm 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.
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 and 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.
Our findings present evidence of the role of Gpr40 agonism in mediating the protective capacities of ESCs against insult from UV-B radiation.
过度暴露于紫外线 B（UV-B）辐射会导致皮肤损伤，从而导致癌症的发展，并降低皮肤作为重要保护屏障的功能。表皮干细胞（ESCs）是多能细胞，负责皮肤再生和修复。暴露于 UV-B 辐射后，ESCs 会产生过量的活性氧（ROS）和炎症细胞因子。然而，ESCs 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，作为各种疾病的潜在治疗靶点正在出现。已经发现 Gpr40 在各种细胞类型中表达。
使用 TL 20W/12RSUV 灯将 ESC 暴露于 25、50 和 100mJ/cm 的 UV-B 下 24 小时。在存在或不存在 25 或 50μMGpr40 激动剂 GW9508 的情况下，将 ESC 用 50mJ/cm 的 UV-B 处理 24 小时。评估 Wnt1 通路和促炎细胞因子的基因表达。为了拮抗 Gpr40 表达，用 10μMGW1100 处理 ESC。
我们的研究结果表明，Gpr40 激动剂可以减少 ROS 的产生以及两种关键促炎细胞因子白细胞介素 1β和 8 的表达。我们证明，Gpr40 的激动剂可以挽救由 UV-B 暴露引起的 和 的减少，从而提高 ESC 抵抗 UV-B 损伤的能力。此外，我们还表明，我们实验中观察到的 Gpr40 激动作用是通过 Wnt/β-catenin 经典信号通路介导的，这表现在 Wnt1 和细胞周期蛋白 D1 的表达上。
我们的研究结果提供了证据表明 Gpr40 激动剂在介导 ESCs 对 UV-B 辐射损伤的保护能力方面发挥作用。
