MSCs-derived exosomes containing miR-486-5p attenuates cerebral ischemia and reperfusion (I/R) injury through inhibiting PTEN

Abstract

Abstract Objectives Our study,s aim is to investigate the impact of MSCs-exosomes on cerebral ischemia and reperfusion (I/R) injury, and the underlying mechanism. Methods Animal model with cerebral ischemia was established by middle cerebral artery occlusion (MCAO), and cell model of Neuro-2a cells was constructed by oxygen-glucose deprivation/reoxygenation (OGD/R). Exosomes (Exo) derived from mesenchymal stem cells (MSCs) of mice were used to inject into mice or stimulate Neuro‐2a cells. Exosomes from MSCs transfected with miR-NC, miR-486-5p mimics, miR-486-5p inhibitor, or sh-PTEN were used to stimulate Neuro‐2a cells. The regulatory axis of miR-486-5p and PTEN was confirmed by rescue experiments. Results Exo-miR-486-5p mimics improved cerebral I/R injury caused neurological deficits and infarct ration, and also attenuated cell apoptosis in vivo. Exo-miR-486-5p mimics notably attenuated OGD/R induced defect on cell viability and inhibited apoptosis of Neuro-2a cells in vitro. Exo-miR-486-5p mimics reduced level of LDH and MDA, while enhanced SOD activity both in brain tissues homogenate of mice and cell supernatant. Mechanically, PTEN was a target of miR-486-5p, and downregulation of PTEN obviously elevated Exo-miR-486-inhibitor caused reduction on cell viability, and reduced it induced elevation on cell apoptosis. Conclusion Our results demonstrated exosomes derived from MSCs might protect against cerebral I/R injury, through miR-486-5p and PTEN axis.