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白细胞介素 21 通过 microRNA-423-5p/紧密连接蛋白 5 信号通路调节炎症性肠病的肠道屏障功能。

IL-21 mediates microRNA-423-5p /claudin-5 signal pathway and intestinal barrier function in inflammatory bowel disease.

机构信息

Department of Neurology, Shanxi Provincial People's Hospital, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China.

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.

出版信息

Aging (Albany NY). 2020 Aug 28;12(16):16099-16110. doi: 10.18632/aging.103566.

Abstract

Inflammatory bowel disease (IBD) is a group of chronic and recurrent nonspecific inflammatory disorders, including Crohn's disease (CD) and ulcerative colitis (UC). Due to the persistent inflammation of intestinal mucosa caused by immune disorders, barrier dysfunction may be an essential cause of the pathogenesis of IBD. Therefore, exploring the mechanism is very important to clarify the pathogenesis of IBD. In our research, we provided evidence of IL-21 function in IBD. The junction complex protein claudin-5 may be a downstream gene of the IL-21. Anti-IL-21 administrated prevented DSS-simulative colitis via recovering claudin-5 expression in the human colonic epithelial cells. Meanwhile, we described that miR-423-5p could be involved in IL-21/ claudin-5 pathway by regulating NF-κB/MAPKs/JNK signaling pathway, which may provide a new therapeutic target for IBD.

摘要

炎症性肠病(IBD)是一组慢性和复发性非特异性炎症性疾病,包括克罗恩病(CD)和溃疡性结肠炎(UC)。由于免疫紊乱导致肠道黏膜持续炎症,屏障功能障碍可能是 IBD 发病机制的重要原因。因此,探讨发病机制对于阐明 IBD 的发病机制非常重要。在我们的研究中,我们提供了 IL-21 在 IBD 中的功能证据。连接复合体蛋白 Claudin-5 可能是 IL-21 的下游基因。抗 IL-21 给药通过恢复人结肠上皮细胞中 Claudin-5 的表达来预防 DSS 模拟的结肠炎。同时,我们描述了 miR-423-5p 可以通过调节 NF-κB/MAPKs/JNK 信号通路参与 IL-21/ Claudin-5 通路,这可能为 IBD 提供新的治疗靶点。

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