Importance of Stratum Corneum Acidification to Restore Skin Barrier Function in Eczematous Diseases.

Eung Ho Choi, Hyun Kang
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Abstract

Skin barrier function relies on three essential components: stratum corneum (SC) lipids, natural moisturizing factors (NMFs), and the acidic pH of the SC surface. Three endogenous pathways contribute to acidity: free fatty acids from phospholipids, trans-urocanic acid from filaggrin (FLG), and the sodium-proton antiporter (NHE1) activity. An acidic SC environment boosts the activity of enzymes to produce ceramides, which are vital for skin health. Conversely, an elevated pH can lead to increased skin infections, reduced lipid-processing enzyme activity, impaired permeability barrier recovery, and compromised integrity and cohesion of the SC due to increased serine protease (SP) activity. Elevated SC pH is observed in neonatal, aged, and inflamed skin. In atopic dermatitis (AD), it results from decreased NMF due to reduced FLG degradation, decreased fatty acids from reduced lamellar body secretion, and reduced lactic acid due to decreased sweating. Moreover, the imbalance between SP and SP inhibitors disrupts barrier homeostasis. However, acidifying the SC can help restore balance and reduce SP activity. Acidic water bathing has been found to be safe and effective for AD. In three different AD murine models, SC acidification prevented the progression of AD to respiratory allergies. In aging skin, a decrease in NHE1 leads to an increased skin pH. Mild acidic skin care products or moisturizers containing NHE1 activators can normalize skin pH and improve barrier function. In conclusion, maintaining the acidity of the SC is crucial for healthy skin barrier function, leading to significant benefits for various skin conditions, such as AD and aging-related skin issues.

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角质层酸化对恢复湿疹患者皮肤屏障功能的重要性
皮肤屏障功能依赖于三种基本成分:角质层(SC)脂质、天然保湿因子(NMF)和角质层表面的酸性 pH 值。造成酸度的三个内源性途径是:磷脂产生的游离脂肪酸、丝胶蛋白(FLG)产生的反式尿囊酸以及钠-质子反转运体(NHE1)的活性。酸性 SC 环境能促进酶的活性,从而产生对皮肤健康至关重要的神经酰胺。相反,pH 值升高会导致皮肤感染增加、脂质加工酶活性降低、渗透屏障恢复受损,以及丝氨酸蛋白酶(SP)活性增加而损害 SC 的完整性和内聚力。在新生儿、老年人和发炎的皮肤中都能观察到皮肤表面 pH 值升高的现象。在特应性皮炎(AD)中,由于FLG降解减少导致NMF降低,片状体分泌减少导致脂肪酸减少,以及出汗减少导致乳酸减少,都会导致SC pH值升高。此外,SP 和 SP 抑制剂之间的失衡也会破坏屏障的平衡。不过,酸化皮肤屏障有助于恢复平衡并降低 SP 的活性。研究发现,酸性水浴对 AD 安全有效。在三种不同的 AD 小鼠模型中,SC 酸化可防止 AD 演变为呼吸道过敏。在老化皮肤中,NHE1 的减少会导致皮肤 pH 值升高。含有 NHE1 激活剂的弱酸性护肤品或保湿霜可使皮肤 pH 值恢复正常,改善皮肤屏障功能。总之,保持 SC 的酸性对皮肤屏障功能的健康至关重要,对各种皮肤病(如过敏性鼻炎和与衰老相关的皮肤问题)有显著的益处。
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