Dermatology Service Veterans Affairs Medical Center, Department of Dermatology, University of California, San Francisco, CA, USA.
Exp Dermatol. 2020 Oct;29(10):1027-1032. doi: 10.1111/exd.14176.
Nitric oxide (NO) regulates a variety of epidermal functions, including epidermal proliferation, differentiation and cutaneous wound healing. However, whether nitric oxide (NO) and its synthetic enzymes regulate epidermal permeability barrier homeostasis is not clear. In the present study, we employed inducible nitric oxide synthase (iNOS) KO mice to explore the role of iNOS in epidermal permeability barrier homeostasis. Our results showed that iNOS mice displayed a comparable levels of basal transepidermal water loss rates, stratum corneum hydration and skin surface pH to their wild-type mice, but epidermal permeability barrier recovery was significantly delayed both 2 and 4 hours after acute barrier disruption by tape stripping. In parallel, expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes were lower in iNOS KO mice versus wild-type controls. Topical applications of two structurally unrelated NO donors to iNOS KO mice improved permeability barrier recovery kinetics and upregulated expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes. Together, these results indicate that iNOS and its product regulate epidermal permeability barrier homeostasis in mice.
一氧化氮（NO）调节多种表皮功能，包括表皮增殖、分化和皮肤创伤愈合。然而，一氧化氮（NO）及其合成酶是否调节表皮渗透性屏障稳态尚不清楚。在本研究中，我们使用诱导型一氧化氮合酶（iNOS）敲除小鼠来探讨 iNOS 在表皮渗透性屏障稳态中的作用。我们的结果表明，iNOS 小鼠的基础经表皮水分流失率、角质层含水量和皮肤表面 pH 值与野生型小鼠相当，但在胶带剥离急性破坏后 2 小时和 4 小时，表皮渗透性屏障的恢复明显延迟。平行地，iNOS 敲除小鼠的表皮分化相关蛋白和脂质合成酶的 mRNA 表达水平较低。两种结构上不相关的 NO 供体的局部应用改善了 iNOS 敲除小鼠的渗透性屏障恢复动力学，并上调了表皮分化相关蛋白和脂质合成酶的 mRNA 表达水平。总之，这些结果表明 iNOS 及其产物调节小鼠的表皮渗透性屏障稳态。
