与炎症性肠病相关的主要遗传因素及其对肠通透性的影响:参与肠道炎症

IF 5.5 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Arthur Mauduit, Emmanuel Mas, Nuria Solà-Tapias, Sandrine Ménard, Frédérick Barreau
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引用次数: 0

摘要

克罗恩病(CD)和溃疡性结肠炎(UC)是炎症性肠病(IBD)的两种主要亚型,是胃肠道慢性复发性炎症性疾病。IBD是一种病因复杂的多因素疾病,涉及环境和遗传因素之间复杂的相互作用。自2001年发现NOD2基因以来,全基因组关联研究已经报道了200多个IBD易感位点。最强的相关性突出了IBD中发生改变的五个主要途径:细菌感知(NOD2),自噬(ATG16L1, IRGM…),内质网应激(XBP1, ARG2…),Th-17免疫途径(il23受体)和维生素D受体(VDR)。IBD的病理生理是由于对改变的肠道微生物群的异常免疫反应。虽然原初运动尚不清楚,但肠道通透性的增加显然参与了这种异常串扰的发生,导致整个组织炎症。因此,过度的肠通透性或“漏肠”已被描述为先于CD的发展。此外,在IBD中,肠通透性被描述为静止性IBD患者复发的敏感预后指标。因此,本综述的目的是强调与IBD相关的主要途径可能有助于改变肠道通透性,从而促进和/或加剧慢性炎症,导致衰弱性疾病的分子和细胞机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Main genetic factors associated with inflammatory bowel diseases and their consequences on intestinal permeability: involvement in gut inflammation.

Crohn's disease (CD) and ulcerative colitis (UC), the two main subtypes of inflammatory bowel diseases (IBD), are chronic relapsing inflammatory disorders of the gastrointestinal tract. IBD are multifactorial diseases with a complex etiology, involving an intricate interaction between environmental and genetic factors. Since the discovery of NOD2 gene in 2001, genome-wide association studies have reported more than 200 IBD susceptibility loci. The strongest associations highlighted five main pathways as altered in IBD: bacterial sensing (NOD2), autophagy (ATG16L1, IRGM…), endoplasmic reticulum stress (XBP1, ARG2…), Th-17 immune pathway (IL23-receptor), and the vitamin D receptors (VDR). The pathophysiology of IBD results from an abnormal immune response toward an altered gut microbiota. Although the primum movens remains unknown, an increased intestinal permeability is clearly involved in the genesis of this abnormal crosstalk, leading to whole tissue inflammation. Thus, an excessive intestinal permeability, or "leaky gut", has been described to precede the development of CD. Moreover, in IBD, intestinal permeability is described to be a sensitive prognostic indicator of relapse in patients with quiescent IBD. Thus, the aim of this review is to highlight the molecular and cellular mechanisms by which the main pathways associated with IBD could contribute to alter the intestinal permeability to favour and/or exacerbate chronic inflammation, leading to debilitating diseases.

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来源期刊
Journal of Gastroenterology
Journal of Gastroenterology 医学-胃肠肝病学
CiteScore
12.20
自引率
1.60%
发文量
99
审稿时长
4-8 weeks
期刊介绍: The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.
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