Transient receptor potential vanilloid 3 activation accelerates keratinocyte migration in vitro but not dermal wound healing in vivo

The non-selective Ca²⁺ permeable transient receptor potential vanilloid 3 (TRPV3) ion channel is highly expressed in mouse keratinocytes, where its activation causes an accelerated cell migration and proliferation via an epidermal growth factor receptor-mediated mechanism in vitro. Therefore, TRPV3 has been proposed as a potential target to accelerate dermal wound healing. In this study, we provide an insight into the effects of TRPV3 activation on mouse keratinocytes and skin wound healing in vitro and in vivo using the newly identified activator of TRPV3 1 (AV3-1). To investigate a possible TRPV3-mediated effect on dermal wound closure in vivo, 2 circular wounds were excised on the back of wild-type and TRPV3 knockout mice and topically treated with AV3-1 or the corresponding vehicle. Unexpectedly, the comparison of neither the wound areas nor the histologic parameters yielded a statistically significant difference between wild-type and TRPV3 knockout wounds. Supporting this notion, AV3-1 treatment could not induce any further acceleration of the wound closure compared to vehicle-treated wounds. Therefore, the described TRPV3-mediated acceleration of keratinocyte migration and proliferation in vitro cannot be directly translated into an in vivo context. SIGNIFICANCE STATEMENT: We here show that deficiency of the transient receptor potential vanilloid 3 (TRPV3) channel impairs mouse keratinocyte migration in vitro. In vivo, however, neither TRPV3 deficiency nor TRPV3 activation by the novel activator of TRPV3 activator 1 (AV3-1) had statistically significant effects on healing rates or reepithelialization of skin wounds.