Zolotas Michael, Schleusener Johannes, Lademann Jürgen, Meinke Martina C, Kokolakis Georgios, Darvin Maxim E
Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Psoriasis Research and Treatment Centre, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Exp Dermatol. 2023 Oct;32(10):1763-1773. doi: 10.1111/exd.14895. Epub 2023 Aug 4.
Psoriasis, one of the most common skin diseases affecting roughly 2%-3% of the world population, is associated with a reduced skin barrier function (SBF) that might play an important role in its pathophysiology. The SBF is provided primarily by the stratum corneum (SC) of the skin. Previous studies have revealed a higher trans-epidermal water loss, lower hydration, abnormal concentration and composition of intercellular lipids, as well as alterations in secondary keratin structure in the psoriatic SC. We compared on molecular level lesional psoriatic skin (LPS) with non-lesional psoriatic skin (nLPS) from 19 patients non-invasively in vivo, using confocal Raman micro-spectroscopy. By analysing the corresponding Raman spectra, we determined SBF-defining parameters of the SC depth-dependently. Our results revealed a lower total lipid concentration, a shift of lamellar lipid organisation towards more gauche-conformers and an increase of the less dense hexagonal lateral packing of the intercellular lipids in LPS. Furthermore, we observed lower natural moisturising factor concentration, lower total water as well as a strong tendency towards less strongly bound and more weakly bound water molecules in LPS. Finally, we detected a less stable secondary keratin structure with increased β-sheets, in contrast to the tertiary structure, showing a higher degree of folded keratin in LPS. These findings clearly suggest structural differences indicating a reduced SBF in LPS, and are discussed in juxtaposition to preceding outcomes for psoriatic and healthy skin. Understanding the alterations of the psoriatic SC provides insights into the exact pathophysiology of psoriasis and paves the way for optimal future treatments.
银屑病是最常见的皮肤病之一,影响着全球约2%-3%的人口,它与皮肤屏障功能(SBF)降低有关,而皮肤屏障功能降低可能在其病理生理学中起重要作用。皮肤屏障功能主要由皮肤的角质层(SC)提供。先前的研究表明,银屑病角质层存在经表皮水分流失增加、水合作用降低、细胞间脂质浓度和组成异常以及角蛋白二级结构改变等情况。我们使用共聚焦拉曼显微光谱技术,在体内对19名患者的银屑病皮损皮肤(LPS)和非皮损皮肤(nLPS)进行了非侵入性的分子水平比较。通过分析相应的拉曼光谱,我们深度依赖性地确定了角质层的皮肤屏障功能定义参数。我们的结果显示,银屑病皮损皮肤中的总脂质浓度较低,层状脂质组织向更多gauche构象转变,细胞间脂质的低密度六方侧向堆积增加。此外,我们观察到银屑病皮损皮肤中的天然保湿因子浓度较低、总水分较低,以及水分子结合力较弱和结合更松散的强烈趋势。最后,与三级结构相比,我们检测到银屑病皮损皮肤中的角蛋白二级结构稳定性较低,β折叠增加,角蛋白折叠程度更高。这些发现清楚地表明了结构差异,表明银屑病皮损皮肤的皮肤屏障功能降低,并与之前关于银屑病皮肤和健康皮肤的研究结果并列讨论。了解银屑病角质层的变化有助于深入了解银屑病的确切病理生理学,并为未来的最佳治疗铺平道路。