Gastroenterology and Hepatology Division, Department of Medicine, University of Rochester School of Medicine, Rochester, New York, USA.
Adv Exp Med Biol. 2012;763:132-48. doi: 10.1007/978-1-4614-4711-5_6.
Intestinal epithelium serves as a key interface between internal body compartments and the gut lumen. The epithelial layer forms a physical barrier that protects the body from the harmful environment of the lumen and also mediates vectorial fluxes of fluids, nutrients and waste. Increased permeability of the epithelial barrier is a common manifestation of different gastrointestinal diseases that enhances body exposure to external pathogens thereby exaggerating mucosal inflammation. Barrier properties of the intestinal epithelium are regulated by specialized adhesive plasma membrane structures known as tight junctions (TJs). It is gengrally believed that disease-related increase in intestinal permeability is caused by defects in TJ structure and functions. This chapter describes the molecular composition of intestinal epithelial TJs, basic mechanisms that regulate TJ functions in healthy gut mucosa as well as molecular events that contribute to increased mucosal permeability during intestinal inflammation. The chapter outlines our current understanding of TJ structure and dynamics and highlights several unresolved questions regarding regulation of this junctional complex under normal conditions and in gastroenterological diseases.
肠上皮作为体内各腔室与肠腔之间的关键界面,发挥着重要作用。上皮层形成了一道物理屏障,保护机体免受肠腔有害物质的侵害,同时还介导着液体、营养物质和废物的定向流动。肠上皮屏障通透性增加是多种胃肠道疾病的常见表现,会增加机体对外源性病原体的暴露,从而加重黏膜炎症。肠上皮的屏障功能由特化的黏附性质膜结构——紧密连接(TJ)来调控。一般认为,与疾病相关的肠上皮通透性增加是由 TJ 结构和功能缺陷引起的。本章描述了肠上皮 TJ 的分子组成,以及健康肠黏膜中调节 TJ 功能的基本机制,还介绍了在肠道炎症期间导致黏膜通透性增加的分子事件。本章概述了我们目前对 TJ 结构和动力学的理解,并强调了在正常条件下和在胃肠病学疾病中调节该连接复合体的几个尚未解决的问题。