Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Prog Lipid Res. 2023 Nov;92:101252. doi: 10.1016/j.plipres.2023.101252. Epub 2023 Sep 4.
The barrier function of the skin is primarily located in the stratum corneum (SC), the outermost layer of the skin. The SC is composed of dead cells with highly organized lipid lamellae in the intercellular space. As the lipid matrix forms the only continuous pathway, the lipids play an important role in the permeation of compounds through the SC. The main lipid classes are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). Analysis of the SC lipid matrix is of crucial importance in understanding the skin barrier function, not only in healthy skin, but also in inflammatory skin diseases with an impaired skin barrier. In this review we provide i) a historical overview of the steps undertaken to obtain information on the lipid composition and organization in SC of healthy skin and inflammatory skin diseases, ii) information on the role CERs, CHOL and FFAs play in the lipid phase behavior of very complex lipid model systems and how this knowledge can be used to understand the deviation in lipid phase behavior in inflammatory skin diseases, iii) knowledge on the role of both, CER subclasses and chain length distribution, on lipid organization and lipid membrane permeability in complex and simple model systems with synthetic CERs, CHOL and FFAs, iv) similarity in lipid phase behavior in SC of different species and complex model systems, and vi) future directions in modulating lipid composition that is expected to improve the skin barrier in inflammatory skin diseases.
皮肤的屏障功能主要位于表皮的角质层（SC）。SC 由细胞死亡组成，细胞间空间内具有高度组织化的类脂双分子层。由于类脂基质形成唯一的连续途径，因此脂质在化合物通过 SC 的渗透中起着重要作用。主要的类脂物类是神经酰胺（CERs）、胆固醇（CHOL）和游离脂肪酸（FFAs）。分析 SC 类脂基质对于理解皮肤屏障功能至关重要，不仅在健康皮肤中，而且在具有受损皮肤屏障的炎症性皮肤病中也是如此。在这篇综述中，我们提供了以下信息：i）获得有关健康皮肤和炎症性皮肤病 SC 中类脂组成和组织信息所采取的步骤的历史概述；ii）CER、CHOL 和 FFAs 在非常复杂的类脂模型系统的类脂相行为中所起的作用的信息，以及如何利用这些知识来理解炎症性皮肤病中类脂相行为的偏差；iii）在具有合成 CER、CHOL 和 FFAs 的复杂和简单模型系统中，CER 亚类和链长分布对类脂组织和类脂膜渗透性的作用的知识；iv）不同物种和复杂模型系统中 SC 的类脂相行为的相似性；v）调节类脂组成以改善炎症性皮肤病中皮肤屏障的未来方向。
