FATTY-ACIDS ARE REQUIRED FOR EPIDERMAL PERMEABILITY BARRIER FUNCTION
FATTY-ACIDS ARE REQUIRED FOR EPIDERMAL PERMEABILITY BARRIER FUNCTION
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DOI：
10.1172/jci116652
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发表时间：
1993-08-01
影响因子：
15.9
通讯作者：
FEINGOLD, KR
中科院分区：
文献类型：
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作者：
MAOQIANG, M;ELIAS, PM;FEINGOLD, KR
渗透性屏障由神经酰胺、甾醇和游离脂肪酸的混合物介导，这些混合物在角质层中排列为细胞外层状双层。尽管之前的研究表明胆固醇和神经酰胺是正常屏障功能所必需的，但目前还没有关于非必需脂肪酸重要性的明确证据。为了确定屏障稳态是否也需要表皮脂肪酸合成，我们在用丙酮或胶带剥离破坏屏障后，应用了 5-(十四烷氧基)-2-呋喃甲酸 (TOFA)（一种乙酰辅酶 A 羧化酶抑制剂）。 TOFA 抑制表皮脂肪酸约 50%，并显着延迟屏障恢复。此外，棕榈酸酯与 TOFA 的共同给药使屏障恢复正常化，表明延迟是由于大量脂肪酸的缺乏造成的。此外，TOFA治疗还会延迟脂质返回角质层，并导致层状体结构异常，层状体是向角质层输送脂质的细胞器。此外，TOFA 处理会破坏角质层间隙内分泌的层状体材料组织成层状双层的情况。最后，通过棕榈酸酯与TOFA的共同应用来纠正板层体和角质层膜结构的这些异常。这些结果表明屏障稳态需要大量脂肪酸。因此，抑制形成细胞外、富含脂质的角质层膜的三种关键脂质中任何一种的表皮合成都会导致屏障稳态受损。
The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis.