Inhibition of microRNA-126-3p attenuates ischemic stroke by targeting endogenous neuroprotective receptor LRP6 in the Wnt/β-catenin signaling pathway.

MicroRNA-126 (miR-126) has emerged as a potential key regulator in ischemic stroke. Yet, its exact mechanism of action is still unexplored. This study aims to investigate whether miR-126 targets and regulates the low-density lipoprotein receptor-related protein (LRP6), an important co-receptor in the Wnt/β-catenin signaling pathway, to reduce ischemic brain injury in mice. C57BL/6 J mice were randomly divided into Sham group, Middle Cerebral Artery Occlusion (MCAO) group, MCAO+miR-126 antagomir group, MCAO+ antagomir NC group, MCAO+miR-126 agomir group and MCAO + agomir NC group. The Garcia nervous system score assessed the neurobehavior of the mice. Infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the extent of cerebral ischemia-reperfusion injury was assessed by Nissl staining. The miR-126 level was detected by real-time PCR, and the apoptosis index was detected by Western blot. A luciferase reporter assay was applied to demonstrate that LRP6 is the target protein of miR-126. The increased expression of miR-126 in MCAO mice inhibits the Wnt/LRP6/β-catenin pathway and enhances neuronal apoptosis. Inhibition of miR-126 alleviates the infarct area, motor ability damage, and apoptosis in MCAO mice. Additionally, Western blot results and luciferase reporter assay showed that inhibition of miR-126 activates the Wnt/β-catenin signaling pathway via LRP6. Our data suggest that inhibition of microRNA-126 attenuates ischemic stroke by targeting endogenous neuroprotective receptor LRP6 in the Wnt/β-catenin signaling pathway.