Neuroprotective Effects of Viral Overexpression of microRNA‐22 in Rat and Cell Models of Cerebral Ischemia‐Reperfusion Injury
Neuroprotective Effects of Viral Overexpression of microRNA‐22 in Rat and Cell Models of Cerebral Ischemia‐Reperfusion Injury
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DOI：
10.1002/jcb.24960
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发表时间：
2015-02
影响因子：
4
通讯作者：
Hou-you Yu;Mingchun Wu;Peng Zhao;Yang Huang;Wei Wang;Wen Yin
中科院分区：
文献类型：
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作者：
Hou-you Yu;Mingchun Wu;Peng Zhao;Yang Huang;Wei Wang;Wen Yin
一些研究报道，microRNA（MIR）参与缺血性疾病（包括脑缺血）的发病机制和进展，并且MIR-22可以抑制炎症反应和细胞凋亡，这有助于缺血/再灌注（I/R）损伤。然而，MIR-22在脑I/R损伤中的具体功能仍远不清楚。本研究旨在研究MIR-22对脑I/R损伤的潜在保护作用及其机制。正如预测的那样，腺病毒介导的MIR-22过表达显著降低了神经评分和梗死面积（P < 0.05）。我们证明，MIR-22过表达导致炎性细胞因子TNF-α、IL-6、考克斯-2和iNOS减少，而IL-10水平增加。MIR-22过表达通过降低NF-κB辅激活因子NCOA 1表达显著抑制NF-κB活性。此外，我们发现MIR-22可以降低皮层神经元的凋亡率。MIR-22可抑制Caspase-3活性，MIR-22过表达后，神经元中抗凋亡基因Bcl-2的表达增加，促凋亡基因Bax的表达减少。我们的研究结果表明，MIR-22可用于治疗脑I/R损伤，其神经保护作用可能归因于炎症和细胞凋亡的减少。J.细胞。116：233-241，2015.© 2014 Wiley Periodicals，Inc.
Several studies have reported that microRNA (MIR) is involved in the pathogenesis and progression of ischemic diseases, including cerebral ischemia, and that MIR‐22 may inhibit the inflammatory response and cell apoptosis, which contribute to ischemia/reperfusion (I/R) injury. However, the specific function of MIR‐22 in cerebral I/R injury remains far from clear. This study aimed to examine the potential protective effect of MIR‐22 against cerebral I/R injury and its mechanism. As predicted, adenovirus‐mediated MIR‐22 overexpression markedly reduced the neurological score and infarct size (P < 0.05). We demonstrated that MIR‐22 overexpression resulted in a reduction in inflammatory cytokines TNF‐α, IL‐6, COX‐2, and iNOS, whereas the level of IL‐10 was enhanced. MIR‐22 overexpression significantly inhibited NF‐κB activity by decreasing NF‐κB coactivator NCOA1 expression. Furthermore, we found that MIR‐22 could reduce the apoptotic rate of cortical neurons. Caspase‐3 activity was inhibited by MIR‐22, and the expression of the anti‐apoptosis gene Bcl‐2 in neurons was increased and that of the pro‐apoptosis gene Bax decreased following MIR‐22 overexpression. Our results suggest that MIR‐22 could be used to treat cerebral I/R injury and that its neuroprotective effect may be attributed to a reduction in inflammation and apoptosis. J. Cell. Biochem. 116: 233–241, 2015. © 2014 Wiley Periodicals, Inc.