Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA; Virginia Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Biochim Biophys Acta Mol Cell Res. 2017 Jul;1864(7):1183-1194. doi: 10.1016/j.bbamcr.2017.03.007. Epub 2017 Mar 18.
The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders.
肠上皮形成了一个关键的保护屏障，将内部器官与肠道腔的有害环境隔离开来。肠道屏障通透性的增加是导致不同炎症性疾病严重程度的常见表现。屏障通透性由上皮细胞黏附连接和紧密连接控制。连接的组装和完整性取决于基本的稳态过程，如细胞分化、细胞骨架的重排和囊泡运输。黏膜炎症期间肠上皮稳态的改变可能会损害顶端连接的结构和重塑，导致肠道屏障通透性增加。在这篇综述中，我们总结了我们对上皮稳态改变如何影响炎症肠道中黏附连接和紧密连接的结构和功能的理解的最新进展。具体来说，我们专注于细胞转录重编程、肌动蛋白细胞骨架的改变以及连接内吞作用和外排作用。我们特别关注基因敲除小鼠模型研究，并讨论这些机制与人类胃肠道疾病的相关性。
