Basis for enhanced barrier function of pigmented skin.

Basis for enhanced barrier function of pigmented skin.
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DOI:
10.1038/jid.2014.187
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发表时间:
2014-09
影响因子:
6.5
通讯作者:
Elias, Peter M.
Elias, Peter M.
中科院分区:
医学1区
文献类型:
--
作者:
Man, Mao-Qiang;Lin, Tzu-Kai;Santiago, Juan L.;Celli, Anna;Zhong, Lily;Huang, Zhi-Ming;Roelandt, Truus;Hupe, Melanie;Sundberg, John P.;Silva, Kathleen A.;Crumrine, Debra;Martin-Ezquerra, Gemma;Trullas, Caries;Sun, Richard;Wakefield, Joan S.;Wei, Maria L.;Feingold, Kenneth R.;Mauro, Theodora M.;Elias, Peter M.

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与浅色皮肤的人相比,深色皮肤的人显示出上级渗透屏障功能。深色皮肤的角质层(SC)的pH值降低可以解释增强的功能,因为酸化浅色人类SC将屏障功能重置为深色水平。在SKH 1(非色素)与SKH 2/J(色素)无毛小鼠中,我们评估了色素依赖性pH值降低如何影响表皮屏障功能。与SKH 1小鼠相比,SKH 2/J小鼠的渗透屏障稳态增强,这与与黑色素颗粒挤出共定位的下SC中pH降低相关。深色的人表皮也显示出外表皮中大量的黑色素挤出。急性屏障破坏和局部碱性pH挑战都加速了SKH 2/J(但不是SKH 1)SC的再酸化,同时诱导黑色素挤出。SKH 2/J小鼠还显示SC酸化酶分泌型磷脂酶A2 f(sPLA 2f)的表达增强。SKH 2/J小鼠屏障功能的增强可能归因于两种酸性pH依赖性神经酰胺生成酶β-葡萄糖脑苷脂酶和酸性鞘磷脂酶的活性增强,导致SC板层双层的加速成熟。最后,与浅色培养物相比,深色着色的人角质形成细胞的器官型培养物显示增强的屏障功能。总之,这些结果表明,着色表皮的上级屏障功能可以在很大程度上归因于黑色素持久性/挤出的pH降低影响和增强的sPLA 2f表达。
Humans with darkly-pigmented skin display superior permeability barrier function in comparison to humans with lightly-pigmented skin. The reduced pH of the stratum corneum (SC) of darkly-pigmented skin could account for enhanced function, because acidifying lightly-pigmented human SC resets barrier function to darkly-pigmented levels. In SKH1 (non-pigmented) vs. SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J vs. SKH1 mice, correlating with a reduced pH in the lower SC that co-localizes with the extrusion of melanin granules. Darkly-pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate re-acidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly-pigmented-bearing human keratinocytes display enhanced barrier function in comparison to lightly-pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression.
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