MicroRNA-93 Downregulation Ameliorates Cerebral Ischemic Injury Through the Nrf2/HO-1 Defense Pathway.
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 H2O2treated 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 H2O2treated neuronal cultures. These results suggested that miR-93 antagomir alleviates ischemic injury through the Nrf2/HO-1 antioxidant pathway.
Key Laboratory of Neurodegenerative Diseases of Liaoning Province and Department of Neurobiology, Jinzhou Medical University, Jinzhou, 121001, China.
Peng
P
Wang
Key Laboratory of Neurodegenerative Diseases of Liaoning Province and Department of Neurobiology, Jinzhou Medical University, Jinzhou, 121001, China.
Xinyu
X
Liang
Key Laboratory of Neurodegenerative Diseases of Liaoning Province and Department of Neurobiology, Jinzhou Medical University, Jinzhou, 121001, China.
Yijun
Y
Lu
Key Laboratory of Molecular Cell Biology and New Drug Development, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Jinzhou, Liaoning, 121001, China.
Xingjian
X
Zhao
Key Laboratory of Molecular Cell Biology and New Drug Development, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Jinzhou, Liaoning, 121001, China. liangjia1@lnmu.edu.cn.
Jia
J
Liang
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D015427:Reperfusion Injury / Q000517:prevention & control; D020521:Stroke / Q000188:drug therapy
D000975:Antioxidants; D035683:MicroRNAs; C551470:Mirn93 microRNA, mouse; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1
HO-1; Ischemic stroke; MiR-93; Nrf2; Oxidative stress