Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
NovaCell Technology, Inc., 77 Cheongamro, Pohang, Gyeongsanbuk-do, Republic of Korea.
Exp Mol Med. 2018 Aug 16;50(8):1-9. doi: 10.1038/s12276-018-0126-x.
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.
胃肠道是一个专门的器官，除了食物消化外，还会发生宿主细胞与复杂环境之间的动态相互作用。黏膜层的化学屏障和细胞免疫系统与上皮细胞层一起，作为抵御外部因素的第一道物理屏障发挥关键作用，并与共生细菌保持共生关系。紧密连接蛋白，包括闭合蛋白、紧密连接蛋白和封闭带蛋白，对于维持上皮屏障完整性至关重要。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，动态调节紧密连接蛋白复合物。这些调节的失衡导致屏障完整性受损，并与病理状况相关。尽管因果关系尚不清楚，但屏障完整性的丧失被认为与炎症性肠病、肥胖和代谢紊乱有关。阐明疾病对屏障完整性的作用及其潜在的调节机制，提高了我们对肠道屏障的理解，从而为开发新的、有效的治疗方法提供了可能。
