Regulatory effects of miR‐146a/b on the function of endothelial progenitor cells in acute ischemic stroke in mice

Abstract

The study aims to explore how microRNA-146a/b (miR-146a/b) regulates the function of endothelial progenitor cells (EPCs) in acute ischemic stroke in mice. Eighty male SPF C57BL/6J mice were evenly divided into the model-6 h, model-12 h, model-24 h (mice suffered from middle cerebral artery occlusion [MCAO] for 6 h, 12 h and model-24 h) and normal groups. EPCs were transfected and assigned into the control, MCAO, MCAO-miR-146a, MCAO-miR-146b and MCAO-miR-146a/b groups. The qRT-PCR was used to detect miR-146a/b expression in EPCs. Expressions of tumor necrosis factor receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1) were detected using western blotting. Cell proliferation and migration of EPCs were testified using CCK-8 assay and scratch test, respectively. Angiogenesis ability of EPCs was observed under microscope. MiR-146a and miR-146b expressions were lower in the model groups than the normal group. There were up-regulated TRAF6 and IRAK1 expressions in the model-6 h, model-12 h and model-24 h groups compared with the normal group. And there were down-regulated TRAF6 and IRAK1 expressions in the MCAO-miR-146a, MCAO-miR-146b and MCAO-miR-146a/b groups than in the MCAO group. Compared with the control group, the proliferation, migration and angiogenesis ability of EPCs were significantly lower in the MCAO group, but higher in the MCAO-miR-146a, MCAO-miR-146b and MCAO-miR-146a/b groups. Besides, the miR-146a/b group showed more enhancement than the MCAO-miR-146a and MCAO-miR-146b groups. MiR-146a/b could down-regulate the TRAF6 and IRAK1 expressions and promote proliferation, migration and angiogenesis ability of EPCs, which was important for recovery of patients with hyperacute ischemic stroke.

<p>The expression of microRNA 146a in patients with ischemic stroke: an observational study</p>

“…Despite the exact function of miRNA 146a downregulation during the acute phase of ischemic stroke is unclear, the previous work by Zhou et al26 demonstrated that the miRNA 146a downregulation has a protective effect on neural cells and it targeted pro-apoptotic genes to reduce apoptosis. Notably, a more recent report found that miRNA 146a/b significantly downregulated tumor necrosis factor receptor-associated factor 6 and IL-1 receptor-associated kinase 1 during the recovery phase of ischemic stroke, which in return favor the proliferation and migration of endothelial progenitor cells 27. miRNA 146a was found to enhance stroke-induced oligodendrogenesis as well 28.…”

MicroRNAs and the Genetic Nexus of Brain Aging, Neuroinflammation, Neurodegeneration, and Brain Trauma

“…Other examples of miRs thought to have important roles in mediating ischemic stroke outcomes include miR-146a/miR-146b [206], miR-9 [207], and miR-130b [208]. Upregulating the expression levels of miR-146a and miR-146b was shown to promote proliferation and angiogenesis of endothelial progenitor cells after acute ischemic stroke in mice [206].…”

“…Other examples of miRs thought to have important roles in mediating ischemic stroke outcomes include miR-146a/miR-146b [206], miR-9 [207], and miR-130b [208]. Upregulating the expression levels of miR-146a and miR-146b was shown to promote proliferation and angiogenesis of endothelial progenitor cells after acute ischemic stroke in mice [206]. While not yet directly linked to stroke, miR-9 has been shown to enhance neural stem cell proliferation, as well as angiogenesis, which could potentially work to enhance post-stroke CNS repair [207].…”

microRNAs and cardiac stem cells in heart development and disease

“…miR-21 mimics can increase integrity of CSCs and improve their proliferation and migration via the target PTEN [12]. Moreover, miR-146a is suggested to enhance migration, proliferation and angiogenesis ability of endothelial progenitor cells [55]. Notably, a single injection of miR-199a and miR-590 mimics immediately after MI in mice is sufficient to induce cardiomyocyte proliferation and promote stable recovery of cardiac function [20].…”