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

The thermosensitive TRPV3 channel contributes to rapid wound healing in oral epithelia
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DOI:
10.1096/fj.14-251314
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发表时间:
2015-01-01
期刊:
影响因子:
4.8
通讯作者:
Kido, Mizuho A.
Kido, Mizuho A.
中科院分区:
生物学2区
文献类型:
--
作者:
Aijima, Reona;Wang, Bing;Kido, Mizuho A.

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口腔提供了一个进入消化道的入口,作为一个保护屏障,防止有害的环境刺激。口腔粘膜由于其位置而容易受伤;尽管如此,它比皮肤具有更快的伤口愈合和更少的疤痕形成。然而,调节这种伤口愈合的分子途径尚不清楚。在这里,我们表明,瞬时受体电位香草素3(TRPV 3),热敏Ca 2+渗透通道,更高的表达在小鼠口腔上皮比在皮肤中的定量RT-PCR。我们发现高于33摄氏度的温度激活TRPV 3并促进口腔上皮细胞增殖。TRPV 3基因敲除(TRPV 3 KO)小鼠口腔上皮细胞的增殖率低于野生型(WT)小鼠。我们使用磨牙拔牙模型研究了TRPV 3对伤口愈合的贡献,发现与WT小鼠相比,TRPV 3 KO小鼠的口腔伤口闭合延迟。TRPV 3 mRNA在创伤组织中表达上调,提示TRPV 3可能有助于口腔创伤修复。我们确定TRPV 3是热诱导的口腔上皮细胞增殖和伤口愈合的重要受体。我们的研究结果表明,TRPV 3激活可能是皮肤和口腔粘膜伤口愈合的潜在治疗靶点。
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 Ca2+-permeable channel, is more highly expressed in murine oral epithelia than in the skin by quantitative RT-PCR. We found that temperatures above 33 degrees 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.