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.