The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia

Abstract

The oral cavity provides an entrance to the alimentary tract to serve as a protective barrier against harmful environmental stimuli. The oral mucosa is susceptible to injury because of its location; nonetheless, it has faster wound healing than the skin and less scar formation. However, the molecular pathways regulating this wound healing are unclear. Here, we show that transient receptor potential vanilloid 3 (TRPV3), a thermosensitive Ca 2+ -permeable channel, is more highly expressed in murine oral epithelia than in the skin by quantitative RT-PCR. We found that temperatures above 33°C activated TRPV3 and promoted oral epithelial cell proliferation. The proliferation rate in the oral epithelia of TRPV3 knockout (TRPV3KO) mice was less than that of wild-type (WT) mice. We investigated the contribution of TRPV3 to wound healing using a molar tooth extraction model and found that oral wound closure was delayed in TRPV3KO mice compared with that in WT mice. TRPV3 mRNA was up-regulated in wounded tissues, suggesting that TRPV3 may contribute to oral wound repair. We identified TRPV3 as an essential receptor in heat-induced oral epithelia proliferation and wound healing. Our findings suggest that TRPV3 activation could be a potential therapeutic target for wound healing in skin and oral mucosa.-Aijima, R., Wang, B., Takao, T., Mihara, H., Kashio, M., Ohsaki, Y., Zhang, J.-Q., Mizuno, A., Suzuki, M., Yamashita, Y., Masuko, S., Goto, M., Tominaga, M., Kido, M. A. The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia. FASEB J. 29, 182-192 (2015). www.fasebj.org Key Words: ambient temperature • oral mucosa • wound repair THE ORAL MUCOSA HAS a highly specialized epithelium that performs essential protective functions against diverse changes, such as chemical, thermal, or mechanical stimuli, in the oral environment. The oral cavity is also the site for sentient responses (1, 2). The oral epithelium is a moist lining membrane in the oral cavity and consists of a stratified squamous epithelium and underlying connective tissues similar to the skin. Although it is continuous with the skin, the oral epithelium is more susceptible to injury because it is exposed to more extensive stimuli than the skin. However, wound repair of the oral mucosa is faster than the skin and recovers with less scar formation (3, 4). Although components in the saliva or a rich vascular supply may contribute to this rapid wound healing (4-6), the molecular mechanisms regulating oral mucosa wound repair are still largely unknown.Transient receptor potential (TRP) channels are a family of Ca 2+ -permeable nonselective cation channels that are responsive to a broad range of environmental stimuli such as temperature, tonicity, or pain (7-9). Among the 28 different mammalian TRP channels, transient receptor potential vanilloid 3 (TRPV3) is uniquely expressed predominantly in keratinocytes and is activated by innocuous warm temperatures above 33°C and natural herbs such as oregano or thyme (10-14). Furthermore, it h...

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