紧密连接
封堵器
势垒函数
微泡
细胞生物学
克洛丹
肠粘膜
外体
小RNA
分泌物
生物
肥大细胞
肠上皮
免疫学
上皮
癌症研究
医学
内科学
内分泌学
基因
生物化学
遗传学
作者
Musheng Li,Jin Zhao,Meiwan Cao,Ruitao Liu,Guanhua Chen,Songyu Li,Yuanwen Xie,Jing Xie,Yang Cheng,Ling Huang,Mingmin Su,Yuxin Xu,Mingyue Zheng,Kejian Zou,Lanlan Geng,Wei Xu,Sitang Gong
标识
DOI:10.1186/s40659-020-00279-2
摘要
Mast cells (MCs) have been found to play a critical role during development of inflammatory bowel disease (IBD) that characterized by dysregulation of inflammation and impaired intestinal barrier function. However, the function of MCs in IBD remains to be fully elucidated.In our study, we used exosomes isolated from human mast cells-1 (HMCs-1) to culture with NCM460, HT-29 or CaCO2 of intestinal epithelial cells (IECs) to investigate the communication between MCs and IECs. We found that MCs-derived exosomes significantly increased intestinal epithelial permeability and destroyed intestinal barrier function, which is attributed to exosome-mediated functional miRNAs were transferred from HMCs-1 into IECs, leading to inhibit tight junction-related proteins expression, including tight junction proteins 1 (TJP1, ZO-1), Occludin (OCLN), Claudin 8 (CLDN8). Microarray and bioinformatic analysis have further revealed that a panel of miRNAs target different tight junction-related proteins. Interestingly, miR-223 is enriched in mast cell-derived exosome, which inhibit CLDN8 expression in IECs, while treatment with miR-223 inhibitor in HT-29 cells significantly reversed the inhibitory effect of HMCs-1-derived exosomes on CLDN 8 expression. Most importantly, enrichment of MCs accumulation in intestinal mucosa of patients with IBD compared with those healthy control.These results indicated that enrichment of exosomal miR-223 from HMCs-1 inhibited CLDN8 expression, leading to destroy intestinal barrier function. These finding provided a novel insight of MCs as a new target for therapeutic treatment of IBD.
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