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Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells
Li, Musheng; Zhao, Junhong; Cao, Meiwan; Liu, Ruitao; Chen, Guanhua; Li, Songyu; Xie, Yuanwen; Xie, Jing; Cheng, Yang; Huang, Ling; Su, Mingmin; Xu, Yuxin; Zheng, Mingyue; Zou, Kejian; Geng, Lanlan; Xu, Wanfu; Gong, Sitang.
  • Li, Musheng; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Zhao, Junhong; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Cao, Meiwan; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Liu, Ruitao; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Chen, Guanhua; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Li, Songyu; Qionghai Hospital of Traditional Chinese Medicine. Department of Clinical Laboratory. Qionghai. CN
  • Xie, Yuanwen; Qionghai Hospital of Traditional Chinese Medicine. Department of Anorectal. Qionghai. CN
  • Xie, Jing; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Cheng, Yang; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Huang, Ling; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Su, Mingmin; Cardiff University. School of Pharmacy and Pharmaceutical Sciences. Department of Cancer Biology and Therapeutics. Wales. GB
  • Xu, Yuxin; Fujian Medical University. School of Public Health. Department of Preventive Medicine. Fuzhou. CN
  • Zheng, Mingyue; Ocean University of China. School of Marine Life Sciences. Qingdao. CN
  • Zou, Kejian; Hainan General Hospital. Department of General Surgery. Haikou. CN
  • Geng, Lanlan; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Xu, Wanfu; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
  • Gong, Sitang; Guangzhou Medical University. Guangzhou Women and Children's Medical Center. Department of Gastroenterology. Guangzhou. CN
Biol. Res ; 53: 12, 2020. tab, graf
Article in English | LILACS | ID: biblio-1100918
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 (lECs) to investigate the communication between MCs and lECs. 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 lECs, 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.
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Full text: Available Index: LILACS (Americas) Main subject: MicroRNAs / Epithelial Cells / Intestinal Mucosa / Mast Cells Limits: Animals / Humans Language: English Journal: Biol. Res Journal subject: Biology Year: 2020 Type: Article Affiliation country: China / United kingdom Institution/Affiliation country: Cardiff University/GB / Fujian Medical University/CN / Guangzhou Medical University/CN / Hainan General Hospital/CN / Ocean University of China/CN / Qionghai Hospital of Traditional Chinese Medicine/CN

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Full text: Available Index: LILACS (Americas) Main subject: MicroRNAs / Epithelial Cells / Intestinal Mucosa / Mast Cells Limits: Animals / Humans Language: English Journal: Biol. Res Journal subject: Biology Year: 2020 Type: Article Affiliation country: China / United kingdom Institution/Affiliation country: Cardiff University/GB / Fujian Medical University/CN / Guangzhou Medical University/CN / Hainan General Hospital/CN / Ocean University of China/CN / Qionghai Hospital of Traditional Chinese Medicine/CN