Shiseido Innovative Science Research & Development Center, Kanazawa-ku, Yokohama, Japan.
Exp Dermatol. 2010 Sep;19(9):791-5. doi: 10.1111/j.1600-0625.2010.01154.x. Epub 2010 Jul 16.
TRPA1 and TRPM8 receptors are activated at low temperature (A1: below 17 degrees C and M8: below 22 degrees C). Recently, we observed that low temperature (below 22 degrees C) induced elevation of intracellular calcium in keratinocytes. Moreover, we demonstrated that topical application of TRPA1 agonists accelerated the recovery of epidermal permeability barrier function after disruption. In this study, we examined the effect of topical application of TRPM8 modulators on epidermal permeability barrier homoeostasis. Immunohistochemical study and RT-PCR confirmed the expression of TRPM8 or TRPM8-like protein in epidermal keratinocytes. Topical application of TRPM8 agonists, menthol and WS 12 accelerated barrier recovery after tape stripping. The effect of WS12 was blocked by a non-selective TRP antagonist, Ruthenium Red, and a TRPM8-specific antagonist, BTCT. Topical application of WS12 also reduced epidermal proliferation associated with barrier disruption under low humidity, and this effect was blocked by BTCT. Our results indicate that TRPM8 or a closely related protein in epidermal keratinocytes plays a role in epidermal permeability barrier homoeostasis and epidermal proliferation after barrier insult.
TRPA1 和 TRPM8 受体在低温下被激活（A1：低于 17 摄氏度，M8：低于 22 摄氏度）。最近，我们观察到低温（低于 22 摄氏度）会诱导角质形成细胞内钙离子水平升高。此外，我们还证明了 TRPA1 激动剂的局部应用可以加速表皮屏障功能破坏后的恢复。在这项研究中，我们研究了 TRPM8 调节剂局部应用对表皮渗透性屏障稳态的影响。免疫组织化学研究和 RT-PCR 证实了 TRPM8 或 TRPM8 样蛋白在表皮角质形成细胞中的表达。TRPM8 激动剂薄荷醇和 WS12 的局部应用加速了胶带剥离后的屏障恢复。WS12 的作用被非选择性 TRP 拮抗剂 Ruthenium Red 和 TRPM8 特异性拮抗剂 BTCT 阻断。WS12 的局部应用还减少了低湿度下与屏障破坏相关的表皮增殖，而这种作用被 BTCT 阻断。我们的结果表明，TRPM8 或表皮角质形成细胞中的密切相关蛋白在表皮渗透性屏障稳态和屏障损伤后的表皮增殖中起作用。
