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黏膜愈合与炎症性肠病:治疗意义与新靶点。

Mucosal healing and inflammatory bowel disease: Therapeutic implications and new targets.

机构信息

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States.

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States.

出版信息

World J Gastroenterol. 2023 Feb 21;29(7):1157-1172. doi: 10.3748/wjg.v29.i7.1157.

Abstract

Mucosal healing (MH) is vital in maintaining homeostasis within the gut and protecting against injury and infections. Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair. However, when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results, particularly inflammatory bowel disease (IBD). Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions, with the mechanisms of regulation just beginning to be understood. Consequently, there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes, so tissue damage in the gastrointestinal tract of patients, even those in clinical remission, persists. With increased understanding of the molecular mechanisms of IBD and MH, tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body's own healing response. In this review, we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.

摘要

黏膜愈合(MH)对于维持肠道内的稳态以及防止损伤和感染至关重要。多种因素和信号通路以动态和协调的方式共同作用,以维持肠道稳态和黏膜再生/修复。然而,当肠道稳态受到慢性干扰并且由于肠上皮屏障自身免疫性疾病的损伤导致炎症免疫反应持续激活时,就会出现自身免疫性疾病,特别是炎症性肠病(IBD)。在这些病理条件下,许多蛋白质和信号通路会失调或受损,其调控机制才刚刚开始被理解。因此,由于疾病和愈合过程的复杂性,仍然缺乏广泛有效的治疗方法来恢复 MH,导致即使在临床缓解的患者中,胃肠道的组织损伤仍然存在。随着对 IBD 和 MH 的分子机制的深入了解,未来可能通过开发增强机体自身愈合反应的治疗方法来减轻自身免疫性疾病引起的组织损伤。在这篇综述中,我们介绍了黏膜愈合的概念及其在 IBD 中的相关性,讨论了 IBD 的发病机制以及改变这些过程和诱导 MH 的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ab/10011951/19997bbb1b53/WJG-29-1157-g001.jpg

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