脳卒中におけるmiR-361-5p/PRMT1経路を介したDICAR/DICAR-JPの治療効果
Zhijun Yu1,2, Aihua Jiang1, Kai Yang3
1Pharmacy, Medical College, Wuhan University of Science and Technology, Wuhan, China.
Background:
Angiogenesis is an important mechanism in stroke therapy. Circular RNA-DICAR is known to protect against diabetes-induced cardiomyocyte pyroptosis. In this study, we examined the effect of DICAR on angiogenesis as well as the therapeutic effect of DICAR-JP, which is its functional domain, against stroke. The mechanism involves the miR-361-5p/PRMT1 signaling pathway. Moreover, the middle cerebral artery occlusion/reperfusion (MCAO) method was used to establish a mouse stroke model in the DICAR-Tg mouse model.
Methods:
AAV9-DICAR-JP was constructed and injected into the cerebral ventricles. Furthermore, tube formation assays were used to evaluate the in vitro activity of DICAR-JP. The blood flow was tested by Laser Speckle Flowgraphy. The expressions of PRMT1 protein expression was evaluated by Western blotting (WB). The binding ability was evaluated by luciferase reporter.
Results:
Results indicated that DICAR-Tg improved neuronal function. AAV9-DICAR-JP increased blood flow in the brain following stroke. DICAR-siRNA upregulated miR-361-5p expression, and overexpression of miR-361-5p significantly reduced PRMT1 expression.
Conclusion:
DICAR/DICAR-JP has potential therapeutic benefits in stroke, which is mediated by the miR-361-5p/PRMT1 signaling pathway.
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