miR-374 improves cerebral ischemia reperfusion injury by targeting Wnt5a

• Published in: Experimental Animals Vol. 70; no. 1; pp. 126 - 136
• Main Authors: Xing, Fangyuan, Liu, Yongrong, Dong, Ruifang, Cheng, Ye
• Format: Journal Article
• Language: English
• Published: Japan Japanese Association for Laboratory Animal Science 01.01.2021; Japan Science and Technology Agency
• Subjects: Animals; Apoptosis; Bcl-2 protein; Bcl-x protein; bcl-X Protein - genetics; bcl-X Protein - metabolism; Blood-brain barrier; Brain damage; Brain injury; brain ischemia; Brain Ischemia - etiology; Brain Ischemia - genetics; Brain Ischemia - therapy; Cerebral blood flow; Cerebral infarction; Disease Models, Animal; Down-Regulation - drug effects; Edema; Gene expression; Gene Expression - genetics; Head injuries; Infarction; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - genetics; Ischemia; Male; MicroRNAs; MicroRNAs - metabolism; MicroRNAs - pharmacology; MicroRNAs - physiology; MicroRNAs - therapeutic use; miR-374; miRNA; Molecular Targeted Therapy; Occlusion; Original; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; Reperfusion; reperfusion injury; Reperfusion Injury - complications; Reperfusion Injury - genetics; Ribonucleic acid; RNA; Wnt protein; Wnt-5a Protein - genetics; Wnt-5a Protein - metabolism; Wnt5a; reperfusion injury; brain ischemia; Wnt5a; miR-374
• ISSN: 1341-1357; 1881-7122
• DOI: 10.1538/expanim.20-0034

To date, studies have demonstrated the potential functions of microRNAs in cerebral ischemia reperfusion (IR) injury. Herein, we established a middle cerebral artery occlusion (MCAO) model in rats and then subjected them to reperfusion to explore the role of microRNA-374 (miR-374) in cerebral IR injury. After reperfusion, the endogenous miR-374 level decreased, and the expression of its target gene, Wnt5a, increased in brain tissues. Intracerebral pretreatment of miR-374 agomir attenuated cerebral damage induced by IR, including neurobehavioral deficits, infarction, cerebral edema and blood-brain barrier disruption. Moreover, rats pretreated with miR-374 agomir showed a remarkable decrease in apoptotic neurons, which was further confirmed by reduced BAX expression as well as increased BCL-2 and BCL-XL expression. A dual-luciferase reporter assay substantiated that Wnt5a was the target gene of miR-374. miR-374 might protect against brain injury by downregulating Wnt5a in rats after IR. Thus, our study provided a novel mechanism of cerebral IR injury from the perspective of miRNA regulation.