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Background   At present, the study has confirmed that the mesenchymal stem cell-derived exosomes (MCSs-Exo) possess cardio-protection in sepsis. Nevertheless, the molecular mechanism of the protection of MSCs-Exo in sepsis remains unknown. Therefore, this research is aimed at studying the molecular mechanism.Methods   The effects of MSCs-Exo and miR-146a-5p in LPS-induced cardiomyocytes (H9C2 cells)  in vitro  were verified by CCK-8, EdU assay, flow cytometry, Western blot assay, and RT-qPCR. The effect of MSCs-Exo  in vivo  was evaluated by CLP-induced sepsis model. The potential gene in MSCs-Exo was verified by bioinformatics analysis, and the potential target of miR-146a-5p was identified by bioinformatics analysis and luciferase reporter assay. At last, the function of miR-146a-5p and its target genes on LPS-induced cardiomyocytes (H9C2 cells)  in vitro  was validated by recuse experiment.Results   Our findings revealed that MSCs-Exo could effectively protect cardiomyocytes of inflammation model  in vitro  and myocardial tissues of sepsis model  in vivo . Meanwhile, we found that miR-146a-5p was a potential gene in MSCs-Exo, and MYBL1 was the target gene of miR-146a-5p and negatively regulated by miR-146a-5p. In addition, miR-146a-5p overexpression promoted proliferation and inhibited apoptosis of LPS-induced cardiomyocytes. The rescue experiment demonstrated that miR-146a-5p could effectively repress the inflammatory response of cardiomyocytes via decreasing MYBL1 expression.Conclusion   This study suggests that miR-146a-5p-bearing MSC-derived exosomes may become an effective treatment for sepsis.

stem cells international

Exosomes Derived from miR-146a-5p-Enriched Mesenchymal Stem Cells Protect the Cardiomyocytes and Myocardial Tissues in the Polymicrobial Sepsis through Regulating MYBL1