Department of Medical Biology and Genetics, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Laboratory of Molecular Biology, Kładki 24, 80-822 Gdańsk, Poland.
Molecules. 2020 Mar 3;25(5):1130. doi: 10.3390/molecules25051130.
Sphingolipids (SLs), which have structural and biological responsibilities in the human epidermis, are importantly involved in the maintenance of the skin barrier and regulate cellular processes, such as the proliferation, differentiation and apoptosis of keratinocytes (KCs). As many dermatologic diseases, including psoriasis (PsO), intricately characterized by perturbations in these cellular processes, are associated with altered composition and unbalanced metabolism of epidermal SLs, more education to precisely determine the role of SLs, especially in the pathogenesis of skin disorders, is needed. PsO is caused by a complex interplay between skin barrier disruption, immune dysregulation, host genetics and environmental triggers. The contribution of particular cellular compartments and organelles in SL metabolism, a process related to dysfunction of lysosomes in PsO, seems to have a significant impact on lysosomal signalling linked to a modulation of the immune-mediated inflammation accompanying this dermatosis and is not fully understood. It is also worth noting that a prominent skin disorder, such as PsO, has diminished levels of the main epidermal SL ceramide (Cer), reflecting altered SL metabolism, that may contribute not only to pathogenesis but also to disease severity and/or progression. This review provides a brief synopsis of the implications of SLs in PsO, aims to elucidate the roles of these molecules in complex cellular processes deregulated in diseased skin tissue and highlights the need for increased research in the field. The significance of SLs as structural and signalling molecules and their actions in inflammation, in which these components are factors responsible for vascular endothelium abnormalities in the development of PsO, are discussed.
鞘脂（SLs）在人类表皮中具有结构和生物学功能，对维持皮肤屏障具有重要作用，并调节细胞过程，如角质形成细胞（KCs）的增殖、分化和凋亡。由于许多皮肤疾病，包括银屑病（PsO），其特征是这些细胞过程的紊乱，与表皮 SLs 的组成改变和代谢失衡有关，因此需要更多的教育来准确确定 SLs 的作用，特别是在皮肤疾病的发病机制中的作用。PsO 是由皮肤屏障破坏、免疫失调、宿主遗传和环境触发因素之间的复杂相互作用引起的。SL 代谢过程中特定细胞区室和细胞器的贡献，以及与 PsO 中溶酶体功能障碍相关的过程，似乎对与免疫介导的炎症相关的溶酶体信号有重大影响，而这种炎症伴随着这种皮肤病，目前尚未完全了解。值得注意的是，一种突出的皮肤疾病，如 PsO，其主要表皮 SL 神经酰胺（Cer）水平降低，反映了 SL 代谢的改变，这不仅可能导致发病机制，而且可能导致疾病的严重程度和/或进展。本综述简要概述了 SLs 在 PsO 中的意义，旨在阐明这些分子在疾病皮肤组织中失调的复杂细胞过程中的作用，并强调需要在该领域进行更多的研究。讨论了 SLs 作为结构和信号分子的重要性及其在炎症中的作用，这些成分是 PsO 发展中血管内皮细胞异常的原因。
