Protective effect of endothelial progenitor cell-derived exosomal microRNA-382-3p on sepsis-induced organ damage and immune suppression in mice.

OBJECTIVE: To explore the role of endothelial progenitor cell (EPC)-derived exosomal microRNA-382-3p (miR-382-3p) in septic injury in mice.

METHODS: A murine model of sepsis was introduced by cecal ligation and puncture (CLP). The model mice were treated with EPC-derived exosomes (Exos). The lung, kidney and liver tissues of mice were collected and stained with hematoxylin and eosin. The lymphocytes in murine spleen tissues, and the proportion and phenotype of the T helper cells (Ths) were examined by flow cytometry. The exosomal miRNAs were screened using a microarray analysis. The expressions of miR-382-3p and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) were measured to explore possible mechanism of Exos in septic injury in mice.

RESULTS: EPC-derived Exos alleviated CLP-induced tissue damage in the lung, kidney and liver tissues in septic mice. They also restored the number of lymphocytes and the concentration of Ths, and reduced the imbalance in Th1 and Th2 cells in mice. The Exos mainly contained miR-382-3p, and miR-382-3p directly targeted BTRC mRNA. Either downregulation of miR-382-3p or upregulation of BTRC blocked the protective roles of Exos in septic injury and immune suppression. Overexpression of BTRC increased the phosphorylation of nuclear factor kappa B (NF-κB) inhibitor α (IκBα) and NF-κB.

CONCLUSION: EPC-derived exosomal miR-382-3p alleviates sepsis-induced organ damage and immune suppression in septic mice through regulating BTRC and the IκBα/NF-κB axis.