Mesenchymal stem cell-derived exosomal miR-143-3p suppresses myocardial ischemia-reperfusion injury by regulating autophagy

Aims: Myocardial ischemia-reperfusion (I/R) injury is considered as a major obstacle of myocardial perfusion to save acute myocardial infarction, and causes a serious threat to human health. An extensive body of evidence has unveiled that mesenchymal stem cells (MSCs) as adult stem cells play a vital role in the field of damaged myocardial regeneration and repair. However, the biological role of MSCs derived-exosomes in the protection of myocardial I/R injury has not been elucidated. Main methods: In this study, we isolated and characterized MSCs from the bone marrow of rats femur and tibia. H9c2 cells were administrated to established the cellular hypoxia-reoxygenation (H/R) model, and co-cultured with MSCs and MSCs-derived exosomes. Key findings: Functional experiments revealed that MSCs and MSCs-derived exosomes inhibited H/R-induced cell apoptosis and cell autophagy. Interestingly, rapamycin as an activator of autophagy reversed the positive effects of MSCs-derived exosomes, while 3-methyladenine (3-MA) as autophagy inhibitor further promoted the effects of MSCs-derived exosomes, indicating MSCs exerted its function on H/R injury by mediating autophagy. Subsequently, we found that CHK2-Beclin2 pathway participated in H/R-induced autophagy. Mechanistically, miR143-3p directly targeted CHK2 and negatively regulated CHK2 expression. Moreover, repression of exosomal miR-143-3p promoted H/R-induced autophagy via CHK2-Beclin2 pathway. Consistent with the results of in vitro experiments, in vivo experiments confirmed that exosomal miR-143-3p effectively reduced cell apoptosis by regulating autophagy via CHK2-Beclin2 pathway. Significance: Collectively, our results indicated that MSCs-derived exosomal miR-143-3p might represent a promising option for the treatment of I/R injury.

Automated summary

The study demonstrated that MSCs-derived exosomes have a protective role in myocardial I/R injury by regulating autophagy. miR-143-3p was found to be involved in H/R-induced myocardial autophagy through the CHK2-Beclin2 pathway, reducing cell apoptosis. These findings suggest that exosomal miR-143-3p may serve as a promising therapeutic option for I/R injury.