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慢性炎症性疾病中的表观遗传变化。

Epigenetic Changes in Chronic Inflammatory Diseases.

作者信息

Fogel O, Richard-Miceli C, Tost J

机构信息

Université Paris Descartes, Hôpital Cochin-Assistance Publique-Hôpitaux de Paris, EULAR Centre of Excellence, Paris, France; Laboratory for Epigenetics and Environment, Centre National de Génotypage, CEA-Institut de Génomique, Evry, France.

Université Paris Descartes, Hôpital Cochin-Assistance Publique-Hôpitaux de Paris, EULAR Centre of Excellence, Paris, France; Immunoregulation Unit, Unité Mixte Pasteur/APHP, Institut Pasteur, Paris, France.

出版信息

Adv Protein Chem Struct Biol. 2017;106:139-189. doi: 10.1016/bs.apcsb.2016.09.003. Epub 2016 Oct 18.

Abstract

The number of people diagnosed with chronic inflammatory diseases has increased noteworthy in the last 40 years. Spondyloarthritis (SpA), inflammatory bowel diseases (IBD), and psoriasis are the most frequent chronic inflammatory diseases, resulting from a combination of genetic predisposition and environmental factors. Epigenetic modifications include DNA methylation, histone modifications, and small and long noncoding RNAs. They are influenced by environmental exposure, life-style, and aging and have recently been shown to be altered in many complex diseases including inflammatory diseases. While epigenetic modifications have been well characterized in other diseases such as cancer and autoimmune diseases, knowledge on changes in inflammatory diseases is lagging behind with some disease-specific differences. While the DNA methylation profile of different cell types in patients with IBD has been relatively well described, less is known on changes implicated in psoriasis, and no systematic genome-wide studies have so far been performed in SpA. In this chapter, we review in detail the reported changes in patterns of DNA methylation and posttranslational histone modifications in chronic inflammatory diseases highlighting potential connections between disease-associated pathophysiological changes such as the dysbiosis of the microbiome or genetic variations associated with disease susceptibility and the epigenome. We also discuss important parameters of meaningful epigenetic studies such as the use of well defined, disease-relevant cell populations, and elude on the potential future of engineering of the epigenome in inflammatory diseases.

摘要

在过去40年中,被诊断患有慢性炎症性疾病的人数显著增加。脊柱关节炎(SpA)、炎症性肠病(IBD)和银屑病是最常见的慢性炎症性疾病,是遗传易感性和环境因素共同作用的结果。表观遗传修饰包括DNA甲基化、组蛋白修饰以及小的和长的非编码RNA。它们受环境暴露、生活方式和衰老的影响,最近已被证明在包括炎症性疾病在内的许多复杂疾病中发生改变。虽然表观遗传修饰在癌症和自身免疫性疾病等其他疾病中已得到充分表征,但关于炎症性疾病变化的知识却滞后,且存在一些疾病特异性差异。虽然IBD患者不同细胞类型的DNA甲基化谱已得到相对较好的描述,但关于银屑病相关变化的了解较少,迄今为止尚未在SpA中进行系统的全基因组研究。在本章中,我们详细回顾了慢性炎症性疾病中报道的DNA甲基化模式和组蛋白翻译后修饰的变化,强调了疾病相关病理生理变化(如微生物群失调或与疾病易感性相关的基因变异)与表观基因组之间的潜在联系。我们还讨论了有意义表观遗传研究的重要参数,如使用明确的、与疾病相关的细胞群体,并探讨了炎症性疾病表观基因组工程的潜在未来。

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