Bone marrow-derived mesenchymal stem cells-derived exosomes prevent oligodendrocyte apoptosis through exosomal miR-134 by targeting caspase-8.

ABSTRACT

Ischemic stroke causes severe brain damage and remains one of the leading causes of morbidity and mortality worldwide. The microRNA-134 (miR-134) is involved in regulating the process of ischemia injury in neural cells and brain with ischemia stroke. The role of miR-134 in ischemic stroke remains poorly understood. The purpose of the current study was to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs)-derived exosomal miR-134 on rat oligodendrocytes (OLs) apoptosis and its underlying mechanism of action. The results demonstrated that levels of miR-134 in BMSCs-exosome decreased but increased incaspase-8 after oxygen-glucose deprivation (OGD) treatment. Exosomal miR-134 significantly inhibited apoptosis by decreasing caspase-8 expression and activity in OGD-treated group cultured with BMSCs-exosome and OLs. In addition, the miR-134 mimics decreased caspase-8 expression in OGD-treated OLs, whereas miR-134 inhibitors exacerbated the changes in the expression of the procaspase-8 and caspase-8 cleaved product proteins caused by OGD. The caspase-8 knockdown using caspase-8 small interfering RNA decreased OLs apoptosis, reversing the improvements that the miR-134 inhibited cells apoptosis by targeting caspase-8. Taken together, these results demonstrated that BMSCs-derived exosomes suppressed OLs apoptosis through exosomal miR-134 by negatively regulating the caspase-8-dependent apoptosis pathway and may, therefore, be a novel potential therapeutic target for ischemic stroke treatment.