Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells

Biological research: BR

article

Li, Musheng¹  Huang, Ling¹  Su, Mingmin²  Xu, Yuxin³  Zheng, Mingyue⁴  Zou, Kejian⁵  Geng, Lanlan¹  Xu, Wanfu¹  Gong, Sitang¹  Zhao, Junhong¹  Cao, Meiwan¹  Liu, Ruitao¹  Chen, Guanhua¹  Li, Songyu⁷  Xie, Yuanwen⁸  Xie, Jing¹  Cheng, Yang¹ 

[1]Department of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University

[2]Department of Cancer Biology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Cardiff University

[3]Department of Preventive Medicine, School of School of Public Health, Fujian Medical University

[4]School of Marine Life Sciences, Ocean University of China

[5]Department of General Surgery, Hainan General Hospital

[6]Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University

[7]Department of Clinical Laboratory, Qionghai Hospital of Traditional Chinese Medicine

[8]Department of Anorectal, Qionghai Hospital of Traditional Chinese Medicine

关键词: Mast cells;    Exosomes;    miR-223;    Claudin 8;    Inflammatory bowel disease;   

DOI  :  10.1186/s40659-020-00279-2

来源: BioMed Central

【 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.

【 授权许可】

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