MSC-derived exosomal miR-34a/c-5p and miR-29b-3p improve intestinal barrier function by targeting the Snail/Claudins signaling pathway.
Life Sci
; 257: 118017, 2020 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-32603821
ABSTRACT
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. MAINMETHODS:
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. KEYFINDINGS:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Mucosa Intestinal
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article