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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


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: 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 [email protected]

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

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