Chen Rui, Tai Yingchun, Zhang Yurong, Wang Li, Yang Yang, Yang Nan, Ma Shuyun, Xue Fangfang, Wang Jianjun
Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, China.
Department of Gynaecology and Obstetrics, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712000, China.
Neurosci Lett. 2019 Jan 18;690:11-16. doi: 10.1016/j.neulet.2018.09.060. Epub 2018 Oct 3.
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.
神经干细胞（NSCs）在哺乳动物大脑中终生存在，并能抵御缺氧缺血性损伤。神经干细胞正日益被视为各种神经系统疾病的新型治疗靶点。先前的研究表明，miR-21可减轻缺氧缺血在多种细胞类型中诱导的凋亡性死亡。然而，miR-21是否在神经干细胞介导的这种保护作用中发挥作用尚不清楚，尤其是在人神经干细胞（hNSCs）中。本研究调查了miR-21是否能预防氧糖剥夺（OGD）诱导的hNSC损伤。在用OGD处理进行挑战时，如CCK-8测定所示，在培养的hNSCs中观察到细胞活力丧失。此外，定量实时PCR（qRT-PCR）分析表明，miR-21的表达呈时间依赖性增加。TUNEL染色和蛋白质印迹分析表明，miR-21的过表达抑制了OGD处理诱导的hNSCs过度死亡。因此，敲低miR-21减弱了对OGD处理观察到的神经保护作用。此外，miR-21过表达后观察到JNK和p38 MAPKs受到抑制，而敲低miR-21则产生相反的效果。我们认为，miR-21通过抑制培养的hNSCs中的JNK和p38途径来预防OGD诱导的hNSCs死亡和凋亡相关蛋白活性。我们的研究结果可能有助于制定策略，以提高缺氧缺血性脑损伤后内源性和移植的神经干细胞的存活率。
