Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: role of cold-sensitive TRP receptors in epidermal permeability barrier homoeostasis
Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: role of cold-sensitive TRP receptors in epidermal permeability barrier homoeostasis
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DOI：
10.1111/j.1600-0625.2010.01154.x
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发表时间：
2010-09-01
影响因子：
3.6
通讯作者：
Denda, Sumiko
中科院分区：
文献类型：
--
作者：
Denda, Mitsuhiro;Tsutsumi, Moe;Denda, Sumiko
TRPA 1和TRPM 8受体在低温下被激活（A1：低于17 ℃，M8：低于22 ℃）。最近，我们观察到低温（低于22摄氏度）诱导角质形成细胞内钙离子升高。此外，我们证明了局部应用TRPA 1激动剂加速了破坏后表皮通透性屏障功能的恢复。在这项研究中，我们研究了局部应用TRPM 8调节剂对表皮通透性屏障稳态的影响。免疫组化和RT-PCR证实TRPM 8或TRPM 8样蛋白在表皮角质形成细胞中表达。TRPM 8激动剂、薄荷醇和WS 12的局部应用加速了胶带剥离后的屏障恢复。WS 12的作用被非选择性TRP拮抗剂钌红和TRPM 8特异性拮抗剂BTCT阻断。局部应用WS 12也减少了与低湿度下屏障破坏相关的表皮增殖，并且这种作用被BTCT阻断。我们的研究结果表明，TRPM 8或表皮角质形成细胞中的密切相关的蛋白质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。
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.