MicroRNA‐130a regulates neurological deficit and angiogenesis in rats with ischaemic stroke by targeting XIAP

Abstract

MicroRNAs (miRNAs) have already been proposed to be implicated in the development of ischaemic stroke. We aim to investigate the role of miR‐130a in the neurological deficit and angiogenesis in rats with ischaemic stroke by regulating X‐linked inhibitor of apoptosis protein (XIAP). Middle cerebral artery occlusion (MCAO) models were established by suture‐occluded method, and MCAO rats were then treated with miR‐130a mimics/inhibitors or/and altered XIAP for detection of changes of rats’ neurological function, nerve damage and angiogenesis in MCAO rats. The oxygen‐glucose deprivation (OGD) cellular models were established and respectively treated to determine the roles of miR‐130a and XIAP in neuronal viability and apoptosis. The expression levels of miR‐130a and XIAP in brain tissues of MCAO rats and OGD‐treated neurons were detected. The binding site between miR‐130a and XIAP was verified by luciferase activity assay. MiR‐130a was overexpressed while XIAP was down‐regulated in MCAO rats and OGD‐treated neurons. In animal models, suppressed miR‐130a improved neurological function, alleviated nerve damage and increased new vessels in brain tissues of rats with MCAO. In cellular models, miR‐130a inhibition promoted neuronal viability and suppressed apoptosis. Inhibited XIAP reversed the effect of inhibited miR‐130a in both MCAO rats and OGD‐treated neurons. XIAP was identified as a target of miR‐130a. Our study reveals that miR‐130a regulates neurological deficit and angiogenesis in rats with MCAO by targeting XIAP.

Activation of PPARβ/δ by DHA induces VEGF-A expression to promote angiogenesis in the cerebral ischemia penumbra

“…In this study, we selected CD31 and α-SMA immuno uorescence double staining to label neovascularization in the penumbra region of cerebral ischemia cortex [40].CD31 and α-SMA are markers of vascular endothelial cells and smooth muscle cells, respectively, and are favorable evidence for tube formation and migration into arteries [41]. We found that compared with MCAO group, the number of new blood vessels in DHA group was signi cantly increased, while the number of new blood vessels in GSK0660 inhibitor group was signi cantly decreased compared with DHA group (all P < 0.05).…”

Longitudinal change in microRNA‐130a expression and its correlation with the risk of developing major adverse cardiovascular and cerebral events in patients undergoing continuous ambulatory peritoneal dialysis

“…High miR-130a levels alleviated cardiac dysfunction and cerebral damage by modulating the PTEN/PI3K/AKT axis 27,28 or targeting the X-linked inhibitor of apoptosis protein 12 to prolong MACCE-free survival in ESRD patients. Nonetheless, there were several limitations in this study.…”

“…Several studies have reported that microRNA-130a (miR-130a) exerts myocardial-protective and neuroprotective effects in vitro and in vivo. 12,13 For example, in in vivo conditions, miR-130a relieves neuronal injury and facilitates neuronal brain tissue growth by downregulating phosphatase and tensin homologous protein (PTEN) expression and upregulating the phosphatidylinositol 3-hydroxy kinase (PI3K) and protein kinase B (Akt) signaling pathways in rats with intracerebral hemorrhage. 14 In addition, miR-130a alleviates human coronary artery endothelial cell injury by inhibiting PTEN expression and activating the PI3K/Akt/endothelial nitric oxide synthase signaling pathway.…”

Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA–SIRT2 Axis and Its Relationship with Aging-Related Diseases

“…However, Deng et al reported opposite effects of miR-130a in MCAO models. They verified that miR-130a was increased in the brains of MCAO model rats and OGD-treated neurons [ 34 ]. In these animal models, suppressed miR-130a improved neurological function and alleviated nerve damage.…”