MicroRNA-376b-5p targets SOX7 to alleviate ischemic brain injury in a mouse model through activating Wnt/β-catenin signaling pathway.

BACKGROUND:Accumulating evidence has reported the role of microRNA (miR) on ischemic brain injury. We aim to investigate the mechanism of miR-376b-5p/Sex-determining region Y-box 7 (SOX7)/Wnt/β-catenin axis in mice with ischemic brain injury. METHODS:Transient middle cerebral artery occlusion (tMCAO) model was established by suture method. Expression levels of miR-376b-5p, SOX7, and Wnt/β-catenin pathway-related proteins (Wnt3a and β-catenin) in brain tissues of tMCAO mice were determined by RT-qPCR and western blot analysis. The target relationship between miR-376b-5p and SOX7 was tested by bioinformatics analysis and luciferase activity assay. The neurological scores of mice were recorded and their behaviors were observed. Moreover, the brain damage, oxidative stress indices, hemoglobin (Hb) content, content of brain water, infarct area, TUNEL positive cells, blood-brain barrier permeability and the number of intact neurons in the ischemic-side brain tissues of tMCAO mice were detected via upregulated miR-376b-5p or downregulated SOX7. RESULTS:In mice with ischemic brain injury, miR-376b-5p targeted and downregulated SOX7 in brain tissues, thus activating the Wnt/β-catenin pathway. The tMCAO mice showed higher neurological scores, severe brain damage, decreased number of neurons, as well as elevated blood-brain barrier permeability, Hb content, cerebral edema and infarct area. These symptoms could be alleviated by miR-376b-5p elevation or SOX7 inhibition. SOX7 overexpression reversed the effects of miR-376b-5p elevation on tMCAO mice. CONCLUSION:Our study suggests that miR-376b-5p could improve the blood-brain barrier permeability, relieve brain edema and decrease infarct area, thus improve ischemic brain injury via the inhibition of SOX7 and activation of Wnt/β-catenin pathway.

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