Radner Franz P W, Fischer Judith
Institute for Human Genetics, University Medical Center Freiburg, Freiburg 79106, Germany.
Institute for Human Genetics, University Medical Center Freiburg, Freiburg 79106, Germany.
Biochim Biophys Acta. 2014 Mar;1841(3):409-15. doi: 10.1016/j.bbalip.2013.07.013. Epub 2013 Aug 6.
Survival in a terrestrial, dry environment necessitates a permeability barrier for regulated permeation of water and electrolytes in the cornified layer of the skin (the stratum corneum) to minimize desiccation of the body. This barrier is formed during cornification and involves a cross-linking of corneocyte proteins as well as an extensive remodeling of lipids. The cleavage of precursor lipids from lamellar bodies by various hydrolytic enzymes generates ceramides, cholesterol, and non-esterified fatty acids for the extracellular lipid lamellae in the stratum corneum. However, the important role of epidermal triacylglycerol (TAG) metabolism during formation of a functional permeability barrier in the skin was only recently discovered. Humans with mutations in the ABHD5/CGI-58 (α/β hydrolase domain containing protein 5, also known as comparative gene identification-58, CGI-58) gene suffer from a defect in TAG catabolism that causes neutral lipid storage disease with ichthyosis. In addition, mice with deficiencies in genes involved in TAG catabolism (Abhd5/Cgi-58 knock-out mice) or TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2, Dgat2 knock-out mice) also develop severe skin permeability barrier dysfunctions and die soon after birth due to increased dehydration. As a result of these defects in epidermal TAG metabolism, humans and mice lack ω-(O)-acylceramides, which leads to malformation of the cornified lipid envelope of the skin. In healthy skin, this epidermal structure provides an interface for the linkage of lamellar membranes with corneocyte proteins to maintain permeability barrier homeostasis. This review focuses on recent advances in the understanding of biochemical mechanisms involved in epidermal neutral lipid metabolism and the generation of a functional skin permeability barrier. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
在陆地干燥环境中生存需要一个渗透屏障，以调节皮肤角质层（即角质层）中水和电解质的渗透，从而使身体脱水降至最低。这个屏障在角质化过程中形成，涉及角质形成细胞蛋白质的交联以及脂质的广泛重塑。各种水解酶从板层小体中切割前体脂质，产生神经酰胺、胆固醇和非酯化脂肪酸，用于角质层中的细胞外脂质层。然而，表皮三酰甘油（TAG）代谢在皮肤功能性渗透屏障形成过程中的重要作用直到最近才被发现。ABHD5/CGI-58（含α/β水解酶结构域蛋白5，也称为比较基因识别-58，CGI-58）基因发生突变的人类患有TAG分解代谢缺陷，导致伴有鱼鳞病的中性脂质贮积病。此外，参与TAG分解代谢的基因缺陷小鼠（Abhd5/Cgi-58基因敲除小鼠）或TAG合成基因缺陷小鼠（酰基辅酶A：二酰甘油酰基转移酶-2，Dgat2基因敲除小鼠）也会出现严重的皮肤渗透屏障功能障碍，并在出生后不久因脱水增加而死亡。由于表皮TAG代谢存在这些缺陷，人类和小鼠缺乏ω-(O)-酰基神经酰胺，这导致皮肤角质化脂质包膜畸形。在健康皮肤中，这种表皮结构为板层膜与角质形成细胞蛋白质的连接提供了一个界面，以维持渗透屏障的稳态。本综述重点介绍了在理解表皮中性脂质代谢以及功能性皮肤渗透屏障形成所涉及的生化机制方面的最新进展。本文是名为“脂质在表皮中的重要作用及其在皮肤屏障形成和维持中的作用”特刊的一部分。客座编辑：肯尼斯·R·费因戈尔德和彼得·埃利亚斯。
