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紧密连接对肠道通透性的调节:对炎症性肠病的影响

Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases.

作者信息

Lee Sung Hee

机构信息

Institute of Pharmaceutical Research and Development, Wonkwang University College of Pharmacy; BK21plus program & Department of Smart Life-Care Convergence, Wonkwang University Graduate School, Iksan, Korea.

出版信息

Intest Res. 2015 Jan;13(1):11-8. doi: 10.5217/ir.2015.13.1.11. Epub 2015 Jan 29.

Abstract

Epithelial tight junctions (TJs) are the key structures regulating paracellular trafficking of macromolecules. The TJ is multi-protein complex that forms a selective permeable seal between adjacent epithelial cells and demarcates the boundary between apical and basolateral membrane domains. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, which can act as a trigger for the development of intestinal and systemic diseases. Inflammatory bowel disease (IBD) patients demonstrate increased intestinal paracellular permeability. Although it remains unclear whether barrier dysfunction precedes disease or results from active inflammation, increased intestinal TJ disruption is observed in IBD patients suggest that dysregulation of TJ barrier integrity may predispose or enhance IBD progression. Therefore, therapeutic target to restore the TJ barrier integrity may provide effective therapeutic and preventive approaches against IBD. This review discusses the molecular structure and regulation of intestinal TJs and the involvement of intestinal TJs in IBD pathogenesis.

摘要

上皮紧密连接(TJs)是调节大分子细胞旁运输的关键结构。紧密连接是一种多蛋白复合物,在相邻上皮细胞之间形成选择性渗透屏障,并划分顶端和基底外侧膜结构域之间的边界。肠道紧密连接屏障的破坏,随后管腔有害分子的渗透,会引起黏膜免疫系统的紊乱和炎症,这可能是肠道和全身性疾病发展的触发因素。炎症性肠病(IBD)患者表现出肠道细胞旁通透性增加。虽然尚不清楚屏障功能障碍是先于疾病还是由活动性炎症导致,但在IBD患者中观察到肠道紧密连接破坏增加,这表明紧密连接屏障完整性的失调可能易患或促进IBD的进展。因此,恢复紧密连接屏障完整性的治疗靶点可能为IBD提供有效的治疗和预防方法。本综述讨论了肠道紧密连接的分子结构和调节以及肠道紧密连接在IBD发病机制中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13fd/4316216/0c506f2aedf8/ir-13-11-g001.jpg

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