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皮肤屏障形成和特应性皮炎(AD)中脂质代谢的转录调控和转录组学分析。

Transcriptional control and transcriptomic analysis of lipid metabolism in skin barrier formation and atopic dermatitis (AD).

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, OSU , Corvallis , OR , USA.

Knight Cancer Institute, Oregon Health & Science University (OHSU) , Portland , OR , USA.

出版信息

Expert Rev Proteomics. 2019 Aug;16(8):627-645. doi: 10.1080/14789450.2019.1646128. Epub 2019 Aug 14.

Abstract

: Atopic dermatitis (AD) is a multifactorial ailment associated with barrier breach and intense systemic inflammation. Several studies over the years have shown the complex interplay of a large number of factors in governing the progression and outcome of AD. In addition to the diverse types of AD resulting due to variation in the intrinsic mechanisms giving rise to AD such as single nucleotide polymorphisms (SNPs), epigenetic alterations or transcriptional changes, extrinsic factors such as age, ancestry, ethnicity, immunological background of the subject, the interactions of the subject with environmental stimuli and existing microbiome in the periphery surrounding the subject account for further heterogeneity in the clinical manifestations of the disease. : Here we have selectively discussed transcriptional regulation of genes associated with skin lipid metabolism in the context of AD. Transcriptional control and transcriptomic changes are just one face of this multifaceted disease known to affect humans and a detailed study concerning those will enable us to develop targeted therapies to deal with the disease. : Large-scale integration of different omics approaches (genomics, epigenomics, transcriptomics, lipidomics, proteomics, metabolomics, effect of exposome) will help identify the potential candidate gene(s) associated with the development of various endotypes of AD.

摘要

特应性皮炎(AD)是一种与屏障破坏和强烈的全身炎症有关的多因素疾病。多年来的多项研究表明,在控制 AD 的进展和结果方面,许多因素之间存在复杂的相互作用。除了由于导致 AD 的内在机制的变异而导致的不同类型的 AD(如单核苷酸多态性(SNP)、表观遗传改变或转录变化)之外,外在因素如年龄、祖籍、种族、主体的免疫学背景、主体与环境刺激的相互作用以及主体周围周围环境中的现有微生物组,也导致了疾病临床表现的进一步异质性。在这里,我们选择性地讨论了与 AD 相关的皮肤脂质代谢基因的转录调控。转录控制和转录组变化只是影响人类的这种多方面疾病的一个方面,对这些方面的详细研究将使我们能够开发针对这些疾病的靶向治疗方法。大规模整合不同的组学方法(基因组学、表观基因组学、转录组学、脂质组学、蛋白质组学、代谢组学、外显子组的影响)将有助于确定与各种 AD 内表型的发展相关的潜在候选基因。

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