MicroRNA-21 attenuates oxygen and glucose deprivation induced apoptotic death in human neural stem cells with inhibition of JNK and p38 MAPK signaling

Abstract

Neural stem cells (NSCs) persist in the mammalian brain throughout life and protect against hypoxia-ischemia injury. NSCs are being increasingly recognized as a novel therapeutic target for various neurological disorders. Previous research indicates that miR-21 attenuates hypoxia-ischemia induced apoptotic death in various cell types. However, whether miR-21 plays a role in this protective effect mediated by NSCs is unknown, particularly in human NSCs (hNSCs). The present study investigated whether miR-21 could prevent hNSC injury induced by oxygen and glucose deprivation (OGD). Upon challenge with OGD treatment, loss of cell viability was observed in cultured hNSCs, as shown by CCK-8 assay. Moreover, quantitative real-time PCR (qRT-PCR) analysis indicated that expression of miR-21 increased in a time-dependent manner. TUNEL staining and Western blotting analysis showed that overexpression of miR-21 inhibited excessive hNSCs death induced by OGD treatment. Accordingly, knock down of miR-21 attenuated the neuroprotective effect observed in response to OGD treatment. Furthermore, JNK and p38 MAPKs inhibition was observed after overexpression of miR-21, and knock down of miR-21 had the opposite effect. We suggest that miR-21 prevents OGD-induced hNSCs death and apoptotic-associated protein activities through inhibiting JNK and p38 pathways in cultured hNSCs. Our findings may help to develop strategies for enhancing resident and transplanted NSCs survival after hypoxia-ischemic brain damage.