Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Pathophysiology, Center of Translational Medicine, University of Tartu, Tartu, Estonia.
J Invest Dermatol. 2018 Jan;138(1):98-108. doi: 10.1016/j.jid.2017.08.036. Epub 2017 Sep 9.
Previous transcriptome analyses underscored the importance of immunological and skin barrier abnormalities in atopic dermatitis (AD). We sought to identify pathogenic pathways involved in AD by comparing the transcriptomes of AD patients stratified for filaggrin (FLG)-null mutations to those of both healthy donors and patients with ichthyosis vulgaris. We applied RNA sequencing to analyze the whole transcriptome of nonlesional skin. We found that 607 genes (476 up-regulated and 131 down-regulated by >2-fold) and 193 genes (172 up-regulated and 21 down-regulated by >2-fold) were differentially expressed when all AD or ichthyosis vulgaris patients were compared with healthy donors, respectively. Expression of genes involved in RNA/protein turnover and adenosine triphosphate synthesis, as well as genes involved in cell death, response to oxidative stress, DNA damage/repair, and autophagy, were significantly enriched in AD skin and, to a lesser extent, in ichthyosis vulgaris skin. FLG-null mutations appear to hardly interfere with current observations. Genes related to xenobiotic metabolism were up-regulated in AD skin only, as were genes related to arachidonic, linoleic, and α-linolenic acid metabolism. Thus, this work newly links AD pathogenesis to aberrant expression of genes related to xenobiotic metabolism.
先前的转录组分析强调了免疫和皮肤屏障异常在特应性皮炎（AD）中的重要性。我们通过比较特应性皮炎患者和寻常型鱼鳞病患者的皮肤转录组，旨在确定 AD 中涉及的致病途径。我们应用 RNA 测序分析了非皮损皮肤的全转录组。结果发现，当所有 AD 或寻常型鱼鳞病患者与健康供体比较时，分别有 607 个基因（476 个上调，131 个下调超过 2 倍）和 193 个基因（172 个上调，21 个下调超过 2 倍）表达差异。AD 皮肤中，涉及 RNA/蛋白质周转和三磷酸腺苷合成的基因以及涉及细胞死亡、氧化应激反应、DNA 损伤/修复和自噬的基因表达显著富集，在寻常型鱼鳞病皮肤中也有一定程度的富集。FLG 无突变似乎对目前的观察结果影响不大。AD 皮肤中与外来生物代谢相关的基因上调，与花生四烯酸、亚油酸和α-亚麻酸代谢相关的基因也上调。因此，这项工作将 AD 的发病机制与与外来生物代谢相关的基因异常表达联系起来。
