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. Res...
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Sociedad de Biología de Chile
2020
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oai:scielo:S0716-976020200001002102020-06-25Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cellsLi,MushengZhao,JunhongCao,MeiwanLiu,RuitaoChen,GuanhuaLi,SongyuXie,YuanwenXie,JingCheng,YangHuang,LingSu,MingminXu,YuxinZheng,MingyueZou,KejianGeng,LanlanXu,WanfuGong,Sitang Mast cells Exosomes miR-223 Claudin 8 Inflammatory bowel disease 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.53 20202020-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100210en10.1186/s40659-020-00279-2 |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
Mast cells Exosomes miR-223 Claudin 8 Inflammatory bowel disease |
| spellingShingle |
Mast cells Exosomes miR-223 Claudin 8 Inflammatory bowel disease 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 Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells |
| 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 (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. |
| author |
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 |
| author_facet |
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 |
| author_sort |
Li,Musheng |
| 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 |
Sociedad de Biología de Chile |
| publishDate |
2020 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100210 |
| work_keys_str_mv |
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| _version_ |
1718441601853816832 |