Mechanisms regulating intestinal barrier integrity and its pathological implications.
Mechanisms regulating intestinal barrier integrity and its pathological implications.
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DOI：
10.1038/s12276-018-0126-x
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发表时间：
2018-08-16
影响因子：
12.8
通讯作者：
Ryu SH
中科院分区：
文献类型：
--
作者：
Chelakkot C;Ghim J;Ryu SH
胃肠道是一个专门的器官，其中除了食物消化外，还发生宿主细胞和复杂环境之间的动态相互作用。与粘膜层和细胞免疫系统的化学屏障一起，上皮细胞层作为对抗外部因素的第一物理屏障发挥关键作用，并与肠道细菌保持共生关系。紧密连接蛋白，包括闭合蛋白，claudins和闭锁小带，是维持上皮屏障完整性的关键。为了允许必需分子的运输并限制有害物质，细胞内信号转导系统和许多细胞外刺激物如细胞因子、小GTP酶和翻译后修饰动态地调节紧密连接蛋白复合物。这些调节的不平衡导致屏障完整性受损，并与病理状况有关。尽管因果关系尚不明确，但屏障完整性的丧失被认为是炎症性肠病、肥胖和代谢紊乱的原因。阐明疾病在屏障完整性和潜在的调控机制中的作用，提高了我们对肠道屏障的理解，从而开发出新型和有效的治疗方法。更好地了解肠道内部的细胞如何允许营养物质进入，同时将有害物质和病原体排除在外，可能会导致炎症性肠病，肥胖和其他疾病的新疗法。由韩国浦项科技大学的Sung Ho Ryu领导的一个研究小组审查了有助于维持肠上皮屏障的调节机制。他们讨论了紧密连接蛋白在相邻细胞之间形成密封的作用，以及放松或收紧这些连接以实现有限运输的各种信号通路。由于遗传、肠道微生物、自身免疫、饮食或其他因素导致的屏障完整性丧失通常与疾病有关，而用药物或益生菌恢复屏障功能有助于改善许多健康问题。
The gastrointestinal tract is a specialized organ in which dynamic interactions between host cells and the complex environment occur in addition to food digestion. Together with the chemical barrier of the mucosal layer and the cellular immune system, the epithelial cell layer performs a pivotal role as the first physical barrier against external factors and maintains a symbiotic relationship with commensal bacteria. The tight junction proteins, including occludin, claudins, and zonula occludens, are crucial for the maintenance of epithelial barrier integrity. To allow the transport of essential molecules and restrict harmful substances, the intracellular signaling transduction system and a number of extracellular stimuli such as cytokines, small GTPases, and post-translational modifications dynamically modulate the tight junction protein complexes. An imbalance in these regulations leads to compromised barrier integrity and is linked with pathological conditions. Despite the obscurity of the causal relationship, the loss of barrier integrity is considered to contribute to inflammatory bowel disease, obesity, and metabolic disorders. The elucidation of the role of diseases in barrier integrity and the underlying regulatory mechanisms have improved our understanding of the intestinal barrier to allow the development of novel and potent therapeutic approaches. A better understanding of how the cells that line the inside of the intestines allow nutrients in, while keeping harmful substances and pathogens out could lead to new therapies for inflammatory bowel disease, obesity, and other conditions. A team from South Korea led by Sung Ho Ryu from Pohang University of Science and Technology review the regulatory mechanisms that help maintain the intestinal epithelial barrier. They discuss the role of tight junction proteins in forming a seal between adjacent cells and the various signaling pathways that loosen or tighten these junctions to enable limited transport. Loss of barrier integrity because of genetics, gut microbes, auto-immunity, diet, or other factors is often implicated in disease, and restoring barrier function with drugs or probiotics could help ameliorate many health problems.