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. 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. 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. The findings here suggest a novel molecular basis for the therapy of intestinal barrier dysfunction.

中文翻译：

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MSC 衍生的外泌体 miR-34a/c-5p 和 miR-29b-3p 通过靶向 Snail/Claudins 信号通路改善肠道屏障功能

间充质干细胞（MSC）衍生的外泌体（MSC-exos）调节不同疾病中的生物学功能，例如肝纤维化、糖尿病和缺血性心脏损伤。然而，MSC 衍生的外泌体对肠道屏障的功能及其潜在机制尚不清楚。通过RT-qPCR评估人正常肠道组织和受损肠道组织中miR-34a/c-5p、miR-29b-3p和Claudin-3的表达。使用共聚焦显微镜、RT-qPCR 和蛋白质印迹测量 MSC 分泌的外泌体对 Caco-2 细胞中 Claudins 的影响。进行双荧光素酶报告基因测定和 RNA 免疫沉淀 (RIP) 测定来研究 miR-34a/c-5p、miR-29b-3p 和 Snail 之间的相互作用。 I/R 诱导的大鼠肠道损伤用于确定 MSC-exos 对肠道屏障功能的体内影响。在这项研究中，我们发现 miR-34a/c-5p、miR-29b-3p 和 Claudin-3 在受损的人肠道组织中表达下调。 MSC-exos 增加 Caco-2 细胞中 Claudin-3、Claudin-2 和 ZO-1 的表达。进一步的研究表明，MSC-exos 通过 Snail 促进 Caco-2 细胞中 Claudin-3、Claudin-2 和 ZO-1 的表达，而 Snail 是 miR-34a/c-5p 和 miR-29b-3p 的靶标。体内实验表明，MSC 衍生的外泌体可以通过 Snail/Claudins 信号通路改善 I/R 诱导的肠道损伤。这里的研究结果为肠屏障功能障碍的治疗提供了新的分子基础。