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MicroRNA-93 Downregulation Ameliorates Cerebral Ischemic Injury Through the Nrf2/HO-1 Defense Pathway

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Abstract

The present study was designed to evaluate the potential role of miR-93 in cerebral ischemic/reperfusion (I/R) injury in mice. The stroke model was produced in C57BL/6 J mice via middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion. And miR-93 antagomir was transfected to down-regulate the miR-93 level. Our results showed that miR-93 levels in the cerebral cortex of mice increased at 24 and 48 h after reperfusion. Importantly, in vivo study demonstrated that treatment with miR-93 antagomir reduced cerebral infarction volume, neural apoptosis and restored the neurological scores. In vitro study demonstrated that miR-93 antagomir attenuated hydrogen peroxide (H2O2)-induced injury. Moreover, miR-93 antagomir suppressed oxidative stress in I/R brain and H2O2 treated cortical neurons. Furthermore, we founded that down-regulation of miR-93 increased the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) and the luciferase reporter assay confirmed that miR-93 directly binds to the predicted 3′-UTR target sites of the nrf2 gene. Finally, we found that knockdown of Nrf2 or HO-1 abolished miR-93 antagomir-induced neuroprotection against oxidative stress in H2O2 treated neuronal cultures. These results suggested that miR-93 antagomir alleviates ischemic injury through the Nrf2/HO-1 antioxidant pathway.

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Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China (NSFC) (Grant No. 81501017), Innovation Foundation for the Unversity Students (Grant No. 201510160000013) and the President Foundation of Jinzhou Medical University (Grant No. XZJJ20140105, XZJJ2015012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Key Laboratory of Neurodegenerative Diseases of Liaoning Province and Department of Neurobiology, Jinzhou Medical University, Jinzhou, 121001, China

    Peng Wang, Xinyu Liang & Yijun Lu

  2. Key Laboratory of Molecular Cell Biology and New Drug Development, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Jinzhou, Liaoning, 121001, China

    Xingjian Zhao & Jia Liang

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  1. Peng Wang
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  2. Xinyu Liang
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Correspondence to Jia Liang.

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Wang, P., Liang, X., Lu, Y. et al. MicroRNA-93 Downregulation Ameliorates Cerebral Ischemic Injury Through the Nrf2/HO-1 Defense Pathway. Neurochem Res 41, 2627–2635 (2016). https://doi.org/10.1007/s11064-016-1975-0

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  • DOI: https://doi.org/10.1007/s11064-016-1975-0

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