MSC-derived exosomal miR-34a/c-5p and miR-29b-3p improve intestinal barrier function by targeting the Snail/Claudins signaling pathway
| Autor: | Qingwen Xu, Pengyuan Xu, Yi-Yun Li, Weiming Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Snail Exosomes 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Chondrocytes Western blot In vivo biology.animal medicine Animals Humans General Pharmacology Toxicology and Pharmaceutics Intestinal Mucosa Claudin Barrier function biology medicine.diagnostic_test Mesenchymal stem cell Mesenchymal Stem Cells General Medicine Microvesicles Cell biology Rats Intestines MicroRNAs 030104 developmental biology Reperfusion Injury Claudins Snail Family Transcription Factors Signal transduction Signal Transduction |
| Zdroj: | Life sciences. 257 |
| ISSN: | 1879-0631 |
| Popis: | Aims Mesenchymal stem cell (MSC)-derived exosomes (MSCs-exos) regulate biological functions in different diseases, such as liver fibrosis, diabetes, and ischaemic heart injury. However, the function of MSC-derived exosomes on the intestinal barrier and the underlying mechanisms are poorly characterized. Main methods The expression of miR-34a/c-5p, miR-29b-3p and Claudin-3 in human normal intestinal tissues and damaged intestinal tissues was evaluated by RT-qPCR. The effect of MSC-secreted exosomes on Claudins in Caco-2 cells was measured by using confocal microscopy, RT-qPCR and Western blot. Dual luciferase reporter assays and RNA immunoprecipitation (RIP) assays were performed to study the interaction between miR-34a/c-5p, miR-29b-3p and Snail. I/R-induced intestinal damage in rats was used to determine the in vivo effect of MSC-exos on intestinal barrier function. Key findings In this study, we found that miR-34a/c-5p, miR-29b-3p and Claudin-3 were downregulated in damaged human intestinal tissues. MSC-exos increased the expression of Claudin-3, Claudin-2 and ZO-1 in Caco-2 cells. Further studies demonstrated that MSC-exos promoted Claudin-3, Claudin-2 and ZO-1 expression in Caco-2 cells by Snail, which was targeted by miR-34a/c-5p and miR-29b-3p. In vivo experiments showed that MSC-derived exosomes could improve I/R-induced intestinal damage through the Snail/Claudins signaling pathway. Significance The findings here suggest a novel molecular basis for the therapy of intestinal barrier dysfunction. |
| Databáze: | OpenAIRE |
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