Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao, China.
Institute of Innovative Drugs, Qingdao University, Qingdao, China.
FASEB J. 2023 Dec;37(12):e23309. doi: 10.1096/fj.202301591RR.
Ultraviolet B (UVB) radiation causes skin injury by trigging excessive calcium influx and signaling cascades in the skin keratinocytes. The heat-sensitive Ca -permeable transient receptor potential vanilloid 3 (TRPV3) channels robustly expressed in the keratinocytes play an important role in skin barrier formation and wound healing. Here, we report that inhibition of cutaneous TRPV3 alleviates UVB radiation-induced skin lesions. In mouse models of ear swelling and dorsal skin injury induced by a single exposure of weak UVB radiation, TRPV3 genes and proteins were upregulated in quantitative real-time PCR and Western blot assays. In accompany with TRPV3 upregulations, the expressions of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were also increased. Knockout of the TRPV3 gene alleviates UVB-induced ear swelling and dorsal skin inflammation. Furthermore, topical applications of two selective TRPV3 inhibitors, osthole and verbascoside, resulted in a dose-dependent attenuation of skin inflammation and lesions. Taken together, our findings demonstrate the causative role of overactive TRPV3 channel function in the development of UVB-induced skin injury. Therefore, topical inhibition of TRPV3 may hold potential therapy or prevention of UVB radiation-induced skin injury.
中波紫外线（UVB）辐射通过触发皮肤角质形成细胞中过量的钙内流和信号级联反应而导致皮肤损伤。在角质形成细胞中强烈表达的热敏 Ca 渗透性瞬时受体电位香草素 3（TRPV3）通道在皮肤屏障形成和伤口愈合中发挥重要作用。在这里，我们报告抑制皮肤 TRPV3 可减轻 UVB 辐射引起的皮肤损伤。在单次弱 UVB 辐射诱导的耳肿胀和背部皮肤损伤的小鼠模型中，实时定量 PCR 和 Western blot 分析显示 TRPV3 基因和蛋白表达上调。随着 TRPV3 的上调，促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的表达也增加。TRPV3 基因敲除可减轻 UVB 诱导的耳肿胀和背部皮肤炎症。此外，两种选择性 TRPV3 抑制剂蛇床子素和毛蕊花糖苷的局部应用可导致皮肤炎症和损伤呈剂量依赖性减弱。总之，我们的研究结果表明，过度活跃的 TRPV3 通道功能在 UVB 诱导的皮肤损伤发展中起因果作用。因此，TRPV3 的局部抑制可能具有治疗或预防 UVB 辐射引起的皮肤损伤的潜力。
