Fat in the skin: Triacylglycerol metabolism in keratinocytes and its role in the development of neutral lipid storage disease.
Fat in the skin: Triacylglycerol metabolism in keratinocytes and its role in the development of neutral lipid storage disease.
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DOI：
10.4161/derm.3.2.15472
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Zechner R
中科院分区：
文献类型：
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作者：
Radner FP;Grond S;Haemmerle G;Lass A;Zechner R
角质形成细胞的分化对于皮肤的发育和皮肤渗透屏障的形成是必不可少的。这一过程涉及脂质的精心重塑。通过β-葡萄糖脑苷脂酶、鞘磷脂酶、磷脂酶和甾醇硫酸酯酶从板层体切割前体脂质，产生神经酰胺、非酯化脂肪酸和胆固醇，用于含脂质的细胞外基质，角质层中的板层膜。三酰甘油（TAG）水解对于形成功能性渗透屏障的重要性直到最近才被认识到。TAG合成（酰基-CoA：二酰基甘油酰基转移酶-2-敲除）或TAG catalysts（比较基因鉴定-58，-CGI-58-敲除）缺陷的小鼠出现严重的渗透性屏障缺陷，并在出生后不久因脱水而死亡。在人类中，CGI-58基因的突变也会导致（非致命性）中性脂质沉积病伴鱼鳞病。由于TAG合成或catalysis缺陷，人类和小鼠缺乏ω-（O）-酰基神经酰胺，其是形成角质细胞脂质包膜的必需脂质前体。这种结构在将富含脂质的板层膜连接到高度交联的角质细胞蛋白中起重要作用。本文综述了表皮中性脂质代谢和功能性皮肤渗透屏障形成所必需的生化机制的现有知识。
Keratinocyte differentiation is essential for skin development and the formation of the skin permeability barrier. This process involves an orchestrated remodeling of lipids. The cleavage of precursor lipids from lamellar bodies by β-glucocerebrosidase, sphingomyelinase, phospholipases and sterol sulfatase generates ceramides, non-esterified fatty acids and cholesterol for the lipid-containing extracellular matrix, the lamellar membranes in the stratum corneum. The importance of triacylglycerol (TAG) hydrolysis for the formation of a functional permeability barrier was only recently appreciated. Mice with defects in TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2-knock-out) or TAG catabolism (comparative gene identification-58, -CGI-58-knock-out) develop severe permeability barrier defects and die soon after birth because of desiccation. In humans, mutations in the CGI-58 gene also cause (non-lethal) neutral lipid storage disease with ichthyosis. As a result of defective TAG synthesis or catabolism, humans and mice lack ω-(O)-acylceramides, which are essential lipid precursors for the formation of the corneocyte lipid envelope. This structure plays an important role in linking the lipid-enriched lamellar membranes to highly cross-linked corneocyte proteins. This review focuses on the current knowledge of biochemical mechanisms that are essential for epidermal neutral lipid metabolism and the formation of a functional skin permeability barrier.