Back to Journals » Neuropsychiatric Disease and Treatment » Volume 16

Protective Role of Astrocyte-Derived Exosomal microRNA-361 in Cerebral Ischemic-Reperfusion Injury by Regulating the AMPK/mTOR Signaling Pathway and Targeting CTSB

Authors Bu X, Li D, Wang F, Sun Q, Zhang Z

Received 30 April 2020

Accepted for publication 28 June 2020

Published 31 July 2020 Volume 2020:16 Pages 1863—1877

DOI https://doi.org/10.2147/NDT.S260748

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Yuping Ning


Xiancong Bu,1 Dong Li,2 Feng Wang,1 Qimeng Sun,1 Zixian Zhang1

1Department of Neurology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, People’s Republic of China; 2Department of Neurology, Zaozhuang Hospital of Zaozhuang Mining Group, Zaozhuang, Shandong 277100, People’s Republic of China

Correspondence: Zixian Zhang Email zixianzhang1344@163.com

Background: Evidence has shown that microRNAs (miRNAs) are implicated in ischemic diseases. Therefore, the aim of the present study was to identify the functions of astrocyte (ATC)-derived exosomal miR-361 on cerebral ischemic-reperfusion (I/R) injury.
Methods: A rat model of cerebral I/R injury was initially established, followed by injection of ATC-derived exosomes. Next, the protective function of ATC-derived exosomes in rats with cerebral I/R injury was evaluated, and then the effect of miR-361 on rats with cerebral I/R injury was evaluated by changing miR-361 expression in exosomes. PC12 cells that underwent oxygen-glucose deprivation/reoxygenation were used to simulate I/R in vitro. The effect of ATC-derived exosomal miR-361 on the viability and apoptosis of OGD/R-treated PC12 cells was also assessed. The bioinformatic analysis predicted the targeted gene of miR-361.
Results: It was found that I/R was damaging to the brain nerves of rats, while ATC-derived exosomal miR-361 relieved nerve damage caused by I/R. Furthermore, the in vitro experiments demonstrated that ATC-derived exosomal miR-361 increased OGD/R-inhibited PC12 cell activity and suppressed cell apoptosis. Bioinformatics predicted that miR-361 targeted cathepsin B (CTSB). CTSB upregulation blocked the protective roles of miR-361. In addition, miR-361 was found to downregulate the AMPK/mTOR signaling pathway by targeting CTSB.
Conclusion: The present study demonstrated that ATC-derived exosomal miR-361 alleviates nerve damage in rats with cerebral I/R injury by targeting CTSB and downregulating the AMPK/mTOR pathway. This may offer novel insights into treatment for I/R injury.

Keywords: cerebral ischemic-reperfusion injury, astrocyte, exosome, microRNA-361, AMPK/mTOR signaling pathway, cathepsin B

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]