<p>Protective Role of Astrocyte-Derived Exosomal <em>microRNA-361</em> in Cerebral Ischemic-Reperfusion Injury by Regulating the <em>AMPK/mTOR</em> Signaling Pathway and Targeting <em>CTSB</em></p>
Xiancong Bu, Dong Li, Feng Wang, Qimeng Sun, Zixian Zhang
Abstract
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 oxygenglucose 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.