Vilardi Aurora, Przyborski Stefan, Mobbs Claire, Rufini Alessandro, Tufarelli Cristina
Cancer Research Centre, University of Leicester, Leicester, LE2 7LX, United Kingdom.
Department of Biosciences, Durham University, Durham, DH1 3LE, United Kingdom.
Cell Death Discov. 2024 May 27;10(1):258. doi: 10.1038/s41420-024-02015-1.
The intestinal wall represents an interactive network regulated by the intestinal epithelium, extracellular matrix (ECM) and mesenchymal compartment. Under healthy physiological conditions, the epithelium undergoes constant renewal and forms an integral and selective barrier. Following damage, the healthy epithelium is restored via a series of signalling pathways that result in remodelling of the scaffolding tissue through finely-regulated proteolysis of the ECM by proteases such as matrix metalloproteinases (MMPs). However, chronic inflammation of the gastrointestinal tract, as occurs in Inflammatory Bowel Disease (IBD), is associated with prolonged disruption of the epithelial barrier and persistent damage to the intestinal mucosa. Increased barrier permeability exhibits distinctive signatures of inflammatory, immunological and ECM components, accompanied by increased ECM proteolytic activity. This narrative review aims to bring together the current knowledge of the interplay between gut barrier, immune and ECM features in health and disease, discussing the role of barrier permeability as a discriminant between homoeostasis and IBD.
肠壁是一个由肠上皮、细胞外基质（ECM）和间充质区室调节的交互网络。在健康的生理条件下，上皮细胞不断更新，形成一个完整且具有选择性的屏障。受损后，健康的上皮细胞通过一系列信号通路得以恢复，这些信号通路通过基质金属蛋白酶（MMPs）等蛋白酶对ECM进行精细调节的蛋白水解作用，从而导致支架组织重塑。然而，如炎症性肠病（IBD）中发生的胃肠道慢性炎症，与上皮屏障的长期破坏和肠黏膜的持续损伤有关。屏障通透性增加表现出炎症、免疫和ECM成分的独特特征，同时伴随着ECM蛋白水解活性的增加。这篇叙述性综述旨在汇集目前关于健康和疾病状态下肠道屏障、免疫和ECM特征之间相互作用的知识，讨论屏障通透性作为区分体内平衡和IBD的判别因素的作用。
