miR-148b Regulates Proliferation and Differentiation of Neural Stem Cells via Wnt/β-Catenin Signaling in Rat Ischemic Stroke Model

Abstract

Stroke is the second leading cause of death worldwide. Stroke induced proliferation and differentiation of neural stem cells (NSCs) that have been proven to participate in ischemic brain repair. However, molecular mechanisms that regulate neurogenesis have not been fully investigated. MicroRNAs play an important role in the neurological repairing process and impact stroke recovery outcome. MiRNA-148b has been reported to regulate cell proliferation in tumor cells, but its role in NSCs after ischemic stroke remains unknown. Here, we found an overexpression of MiRNA-148b in subventricular zone (SVZ) of rat ischemic brain. In original cultured ischemic NSCs, transfection of MiRNA-148b mimic or inhibitor could suppress or enhance the expression of Wnt-1, β-catenin, and Cyclin D1, hence effected wnt/β-catenin signaling. MiRNA-148b inhibitor promoted NSCs proliferation and differentiation into newborn neural and astrocytes, and this action could be silenced with knockdown of Wnt-1. In middle cerebral artery occlusion (MCAo) rats, injection of MiRNA-148b inhibitor could reduce ischemic lesion volume and improve neurological function outcome. Collectively, our data suggest that MiRNA-148b suppressed wnt/β-catenin signaling attenuates proliferation and differentiation of neural stem cells, these findings shed new light on the role of MiRNA-148b in the recovery process during the stroke and contribute to the novel therapy strategy.

Inhibition of miR‐148b ameliorates myocardial ischemia/reperfusion injury via regulation of Wnt/β‐catenin signaling pathway

“…In agreement with our study, J. Wang et al (2017) also reported that miR-148b, through upregulating Wnt-1, activated Wnt/β-catenin pathway to enhance the expression of cyclin D1, thus facilitating the proliferation of nerve stem cells while reducing the infarction volume in rats with ischemic stroke, miR-148b inhibitor can upregulate the Bcl-2/ Bax ratio and C-myc through activating the Wnt/β-catenin pathway to promote the proliferation and suppress the apoptosis in VMSCs in the study of L. Zhang, Cheng, et al (2018). Furthermore, we also discovered that the protective effect of miR-148b inhibitor against the H/R injury was abolished by Wnt-1 siRNA, which further confirmed that the regulatory role of miR-148b in myocardial I/R injury could be achieved by targeting Wnt-1.…”

Inhibition of microRNA‐148b‐3p alleviates oxygen‐glucose deprivation/reoxygenation‐induced apoptosis and oxidative stress in HT22 hippocampal neuron via reinforcing Sestrin2/Nrf2 signalling

“…These results suggest that miR‐148b‐3p inhibition provides a neuroprotective effect in OGD/R‐injured neurons, findings that implicate miR‐148b‐3p in cerebral ischaemia/reperfusion injury. Interestingly, a recent study revealed that miR‐148b‐3p inhibition promotes the proliferation and differentiation of neural stem cells into neurons and astrocytes, which is beneficial for improving neurological recovery in the rodent model of cerebral ischaemia/reperfusion injury . Therefore, these studies, along with our findings, support the idea that miR‐148b‐3p inhibition is a novel therapeutic strategy for providing neuroprotection against cerebral ischaemia/reperfusion injury.…”

“…*P < .05 beneficial for improving neurological recovery in the rodent model of cerebral ischaemia/reperfusion injury. 37 Therefore, these studies, along with our findings, support the idea that miR-148b-3p inhibition is a novel therapeutic strategy for providing neuroprotection against cerebral ischaemia/reperfusion injury.…”

Treadmill exercise promotes neurogenesis and myelin repair via upregulating Wnt/β‑catenin signaling pathways in the juvenile brain following focal cerebral ischemia/reperfusion

“…Research showed that intranasal administration of Wnt3a can enhance the neuroprotection and regeneration of the Wnt signaling pathway after focal ischemic stroke in mice (19). Previous studies have shown that Wnt signal transduction is the main regulator of hippocampal neurogenesis in adults (20)(21)(22)(23). Activating the Wnt pathway in vivo and in vitro was shown to increase neurogenesis, and blocking the Wnt pathway inhibited the proliferation and differentiation of rat neural progenitor cells (NPcs) (20).…”