Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition
Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition
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DOI：
10.1016/j.jdermsci.2017.05.005
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发表时间：
2017-10-01
影响因子：
4.6
通讯作者：
Bouwstra, Joke
中科院分区：
文献类型：
--
作者：
Danso, Mogbekeloluwa;Boiten, Walter;Bouwstra, Joke
背景资料：特应性皮炎（AD）皮肤中的屏障功能障碍与角质层（SC）脂质异常相关，包括整体脂质含量降低、神经酰胺（CER）和游离脂肪酸（FFA）链长缩短以及CER亚类水平改变。然而，脂质组成的这些变化的根本原因还没有完全investigated.Aim：我们研究了与对照皮肤相比，AD皮肤中CER和FFA生物合成酶的表达是否改变，并确定酶表达的变化是否与脂质组成的变化有关。在AD患者和对照中，分析了与SC脂质组成相关的参与FFA和CER生物合成的酶的表达。这些酶包括参与FFA合成的硬脂酰CoA去饱和酶（SCD）、延长酶1（EMLVL 1）和EMLVL 6，以及参与CER合成的β-葡糖脑苷脂酶（GBA）、酸性鞘磷脂酶（aSmase）、神经酰胺合酶3（CerS 3）。在TH 2处理的人类皮肤等价物（AD HSEs）模仿病变AD skin，这些酶的mRNA表达investigated.Results：结果揭示了一个改变的表达SCD和CD 4VL 1在AD病变皮肤。这伴随着功能变化，表现为AD病变皮肤中不饱和FFA（SCD）增加和FFA C22-C28（FFA VL 1）减少。GBA、aSmase和CerS 3的表达也发生了变化。AD皮损中CER组成表现出相应的变化，如CER AS和NS（aSmase）增加和酯化ω-羟基CER（CerS 3）减少。在支持AD皮肤的结果，AD HSEs表现出降低mRNA的VL 1，GBA和Smaselevels.Conclusion：这项研究表明，参与SC脂质合成的关键酶的表达的改变有助于在AD皮肤和炎症的脂质组成的变化可能会影响这些酶的表达。(C)2017日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: The barrier dysfunction in atopic dermatitis (AD) skin correlates with stratum corneum (SC) lipid abnormalities including reduction of global lipid content, shorter ceramide (CER) as well as free fatty acid (FFA) chain length and altered CER subclass levels. However, the underlying cause of these changes in lipid composition has not been fully investigated.Aim: We investigated whether the expression of CER and FFA biosynthesis enzymes are altered in AD skin compared with control skin and determine whether changes in enzyme expression can be related with changes in lipid composition.Methods: In AD patients and controls the expression of enzymes involved in the biosynthesis of FFAs and CERs was analyzed in relation to the SC lipid composition. These enzymes include stearoyl CoA desaturase (SCD), elongase 1 (ELOVL1) and ELOVL6 involved in FFA synthesis and beta-glucocerebrosidase (GBA), acid-sphingomyelinase (aSmase), ceramide synthase 3 (CerS3) involved in CER synthesis. In TH2 treated human skin equivalents (AD HSEs) mimicking lesional AD skin, the mRNA expression of these enzymes was investigated.Results: The results reveal an altered expression of SCD and ELOVL1 in AD lesional skin. This was accompanied by functional changes displayed by increased unsaturated FFAs (SCD) and reduced FFA C22-C28 (ELOVL1) in AD lesional skin. The expression of GBA, aSmase and CerS3 were also altered in lesional skin. The CER composition in AD lesional skin showed corresponding changes such as increased CER AS and NS (aSmase) and decreased esterified omega-hydroxy CERs (CerS3). In support of the results from AD skin, the AD HSEs showed reduced mRNA ELOVL1, GBA and a Smase levels.Conclusion: This study shows that alterations in the expression of key enzymes involved in SC lipid synthesis contribute to changes in the lipid composition in AD skin and inflammation may influence expression of these enzymes. (C) 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.