Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells
Abstract Background 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. Result...
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doaj-d205da07cf354d1da98233dc7ae8f9e52020-11-25T02:52:31ZengBMCBiological Research0717-62872020-03-0153111110.1186/s40659-020-00279-2Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cellsMusheng Li0Junhong Zhao1Meiwan Cao2Ruitao Liu3Guanhua Chen4Songyu Li5Yuanwen Xie6Jing Xie7Yang Cheng8Ling Huang9Mingmin Su10Yuxin Xu11Mingyue Zheng12Kejian Zou13Lanlan Geng14Wanfu Xu15Sitang Gong16Department of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Clinical Laboratory, Qionghai Hospital of Traditional Chinese MedicineDepartment of Anorectal, Qionghai Hospital of Traditional Chinese MedicineDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Cancer Biology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Cardiff UniversityDepartment of Preventive Medicine, School of School of Public Health, Fujian Medical UniversitySchool of Marine Life Sciences, Ocean University of ChinaDepartment of General Surgery, Hainan General HospitalDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityAbstract Background 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s40659-020-00279-2Mast cellsExosomesmiR-223Claudin 8Inflammatory bowel disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Musheng Li Junhong 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 Wanfu Xu Sitang Gong |
spellingShingle |
Musheng Li Junhong 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 Wanfu Xu Sitang Gong Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells Biological Research Mast cells Exosomes miR-223 Claudin 8 Inflammatory bowel disease |
author_facet |
Musheng Li Junhong 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 Wanfu Xu Sitang Gong |
author_sort |
Musheng Li |
title |
Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells |
title_short |
Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells |
title_full |
Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells |
title_fullStr |
Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells |
title_full_unstemmed |
Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells |
title_sort |
mast cells-derived mir-223 destroys intestinal barrier function by inhibition of cldn8 expression in intestinal epithelial cells |
publisher |
BMC |
series |
Biological Research |
issn |
0717-6287 |
publishDate |
2020-03-01 |
description |
Abstract Background 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. Results 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. Conclusions 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. |
topic |
Mast cells Exosomes miR-223 Claudin 8 Inflammatory bowel disease |
url |
http://link.springer.com/article/10.1186/s40659-020-00279-2 |
work_keys_str_mv |
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