Inhibition of cutaneous heat‐sensitive Ca2+‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice

Abstract

AbstractUltraviolet B (UVB) radiation causes skin injury by trigging excessive calcium influx and signaling cascades in the skin keratinocytes. The heat‐sensitive Ca2+‐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.