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Profiling transcriptomic changes and signaling pathways in atopic dermatitis by integrative analyses on multiple databases
Molecular Genetics and Genomics ( IF 3.1 ) Pub Date : 2021-01-13 , DOI: 10.1007/s00438-020-01754-x
Yubin Xu , Saizhen Chen , Jinguang Chen

Atopic dermatitis (AD) is a condition driven by T cell-mediated immune response. Targeted therapy of AD is challenging due to its complex pathogenesis. In the current study, by analyzing multiple expression and network datasets, we aimed at: (1) identifying important transcriptomic signatures/profiles for AD to seek potential therapeutic targets and (2) discovering key regulators in the pathogenesis of AD. Our differentially expressed gene (DEG) analysis revealed multiple genes involved in immune response and dermal structural integrity. Functional enrichment analyses suggested that signaling pathways involved in epidermal barrier and inflammation and immunity are overrepresented in lesional AD. Protein–protein interaction (PPI) network and causal interactions analyses highlighted the roles of regulators of epidermal integrity and immune response in the pathogenesis of AD. Prominently, a negative regulator of the B-cell receptor-mediated immune response, PKCβ, has been suggested in the predicted pathogenesis model for AD, implying B cell-mediated immune response may play an equally important role as that of the T cell-mediated immune response in AD. A further search in a perturbagen database has identified small molecular drugs that may alter expression profiles of key regulators in the pathogenesis of AD. In this study, we propose a systemic multi-omics strategy incorporating multiple analyses on various datasets of transcriptomes, diseases, and pharmacology. Such integrative analyses will effectively advance our understanding on the pathogenesis and treatment of AD.



中文翻译:

通过多个数据库的综合分析来分析特应性皮炎的转录组变化和信号通路

特应性皮炎(AD)是由T细胞介导的免疫反应驱动的疾病。AD的靶向治疗由于其复杂的发病机理而具有挑战性。在当前的研究中,我们通过分析多个表达和网络数据集,旨在:(1)识别AD的重要转录组特征/特征,以寻找潜在的治疗靶标;(2)发现AD发病机理中的关键调控因子。我们的差异表达基因(DEG)分析揭示了涉及免疫反应和皮肤结构完整性的多个基因。功能富集分析表明,与表皮屏障,炎症和免疫有关的信号传导通路在病灶性AD中被过度代表。蛋白质-蛋白质相互作用(PPI)网络和因果相互作用分析强调了表皮完整性和免疫应答调节剂在AD发病机理中的作用。突出地,已经在AD的预测发病机理模型中提出了B细胞受体介导的免疫应答的负调节剂PKCβ,这暗示B细胞介导的免疫应答可能起着与T细胞介导的免疫应答同样重要的作用。 AD的免疫反应。在微扰源数据库中的进一步搜索已经确定了小分子药物,这些药物可能会改变AD发病机理中关键调节因子的表达谱。在这项研究中,我们提出了一种系统的多组学策略,该策略结合了对转录组,疾病和药理学的各种数据集的多种分析。

更新日期:2021-01-13
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