Lentivirus-Mediated Overexpression of MicroRNA-210 Improves Long-Term Outcomes after Focal Cerebral Ischemia in Mice
Lentivirus-Mediated Overexpression of MicroRNA-210 Improves Long-Term Outcomes after Focal Cerebral Ischemia in Mice
复制标题
慢病毒介导的 MicroRNA-210 过表达可改善小鼠局灶性脑缺血后的长期结果
DOI：
10.1111/cns.12589
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发表时间：
2016-12-01
影响因子：
5.5
通讯作者：
Yang, Guo-Yuan
中科院分区：
文献类型：
--
作者：
Zeng, Li-Li;He, Xiao-Song;Yang, Guo-Yuan
目的MicroRNAs在缺血性脑损伤的发病机制和脑缺血后的修复过程中发挥重要作用。然而，关键的miRNAs及其在这些过程中的功能仍不清楚。用独创性通径分析法对预测的差异网络进行了分析。选择关键的MicroRNA，并在小鼠缺血模型中进一步研究其功能。结果发现24种MicroRNA在脑卒中患者中的表达与对照组相比存在差异（P <0. 05）。生物信息学分析显示，脑卒中级联反应中得分最高的MicroRNA调控网络由10种MicroRNA组成，包括关键的缺氧相关miR-210及其预测的下游靶点脑源性神经营养因子（BDNF）。慢病毒介导的miR-210过表达可增加缺血小鼠脑内微血管密度和神经前体细胞数量（P < 0.05），并改善缺血小鼠的神经行为结局（P < 0.05）。miR-210上调增加正常和缺血小鼠脑中mBDNF/proBDNF蛋白表达。结论miR-210是缺血性脑卒中相关的重要microRNA，是脑卒中治疗的潜在靶点。
AimsMicroRNAs play an important role in the pathogenesis of ischemic brain injury and in the repair process during postischemic condition. However, the key miRNAs and their function in these processes remain unclear.MethodsCirculating blood MicroRNAs profiles were examined in the ischemic stroke patients. The predicted network of difference was analyzed by ingenuity pathway analysis. The key MicroRNAs were selected, and the function was further studied in a mouse ischemia model. The predicted downstream target was confirmed.ResultsWe found that 24 MicroRNAs were differently expressed in stroke patients compared to the control (P < 0.05). Bioinformatic analysis showed a MicroRNAs regulated network with the highest score in the stroke cascade, which was consisted of 10 MicroRNAs including key hypoxia-related miR-210 and its predicted downstream target brain derived neurotrophic factor (BDNF). Lentivirus-mediated miR-210 overexpression enhanced the microvessel density and the number of neural progenitor cells in the ischemic mouse brain (P < 0.05) and improved neurobehavioral outcomes in the ischemic mouse (P < 0.05). MiR-210 upregulation increased mBDNF/proBDNF protein expression in the normal and ischemic mouse brain. The dual-luciferase reporter assay identified that BDNF was the direct target of miR-210.ConclusionMiR-210 is a crucial ischemic stroke-associated MicroRNAs and a potential target for the stroke therapy.