Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients
Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients
复制标题
DOI：
10.1194/jlr.p030338
复制
发表时间：
2012-12-01
影响因子：
6.5
通讯作者：
Bouwstra, Joke A.
中科院分区：
文献类型：
--
作者：
Janssens, Michelle;van Smeden, Jeroen;Bouwstra, Joke A.
特应性湿疹（AE）的一个标志是皮肤屏障功能障碍。角质层（SC）中的脂质（主要是神经酰胺、脂肪酸和胆固醇）对屏障功能至关重要，但其与AE相关的作用尚不清楚。丝聚蛋白是一种上皮屏障蛋白，在AE的发病机制中起着重要作用。然而，AE相关屏障功能障碍的确切原因在很大程度上是未知的。在这项研究中，神经酰胺的组成和脂质组织在非病变SC的AE患者和对照组进行了全面的分析，通过质谱，红外光谱和X-射线衍射。此外，还检查了皮肤屏障和疾病的临床状态。在AE患者的SC中具有极短链长度的神经酰胺水平急剧增加，这导致异常的脂质组织和皮肤屏障功能降低。SC脂质性质的变化与疾病的严重程度相关，但独立于聚丝蛋白突变。jlr我们第一次证明神经酰胺链长度和脂质组织的变化与AE患者的非病变皮肤中的皮肤屏障缺陷直接相关。我们设想这些见解将为治疗和预防AE提供新的治疗入口。Janssens，M.，J.货车斯梅登，G. S.古里斯，W.布拉斯，G.作者声明：John，R. J. Vreeken，T. Hankemeier，S.凯济奇河Wolterbeek，A. P. Lavrijsen和J. A.布斯特拉特应性湿疹患者短链神经酰胺的增加与脂质组织改变和屏障功能降低相关。J. Lipid Res. 2012. 53：2755-2766。
A hallmark of atopic eczema (AE) is skin barrier dysfunction. Lipids in the stratum corneum (SC), primarily ceramides, fatty acids, and cholesterol, are crucial for the barrier function, but their role in relation to AE is indistinct. Filaggrin is an epithelial barrier protein with a central role in the pathogenesis of AE. Nevertheless, the precise causes of AE-associated barrier dysfunction are largely unknown. In this study, a comprehensive analysis of ceramide composition and lipid organization in nonlesional SC of AE patients and control subjects was performed by means of mass spectrometry, infrared spectroscopy, and X-ray diffraction. In addition, the skin barrier and clinical state of the disease were examined. The level of ceramides with an extreme short chain length is drastically increased in SC of AE patients, which leads to an aberrant lipid organization and a decreased skin barrier function. Changes in SC lipid properties correlate with disease severity but are independent of filaggrin mutations. jlr We demonstrate for the fi rst time that changes in ceramide chain length and lipid organization are directly correlated with the skin barrier defects in nonlesional skin of AE patients. We envisage that these insights will provide a new therapeutic entry in therapy and prevention of AE.-Janssens, M., J. van Smeden, G. S. Gooris, W. Bras, G. Portale, P. J. Caspers, R. J. Vreeken, T. Hankemeier, S. Kezic, R. Wolterbeek, A. P. Lavrijsen, and J. A. Bouwstra. Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. J. Lipid Res. 2012. 53: 2755-2766.