Studies demonstrate that microRNA-126 plays a critical role in promoting angiogenesis. However, its effects on angiogenesis following ischemic stroke are unclear. Here, we explored the effect of microRNA-126-3p and microRNA-126-5p on angiogenesis and neurogenesis after brain ischemia. We demonstrated that both microRNA (miRNA)-126-3p and microRNA-126-5p increased the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with the scrambled miRNA control (p < 0.05). Transferring microRNA-126 into a mouse middle cerebral artery occlusion model via lentivirus, we found that microRNA-126 overexpression increased the number of CD31/BrdU (5-bromo-2′-deoxyuridine-positive) proliferating endothelial cells and DCX/BrdU neuroblasts in the ischemic mouse brain, improved neurobehavioral outcomes (p < 0.05), and reduced brain atrophy volume (p < 0.05) compared with control mice. Western blot results showed that AKT and ERK signaling pathways were activated in the lentiviral-microRNA-126-treated group (p < 0.05). Both PCR and western blot results demonstrated that tyrosine-protein phosphatase non-receptor type 9 (PTPN9) was decreased in the lentiviral-microRNA-126-treated group (p < 0.05). Dual-luciferase gene reporter assay also showed that was the direct target of microRNA-126-3p and microRNA-126-5p in the ischemic brain. We demonstrated that microRNA-126-3p and microRNA-126-5p promoted angiogenesis and neurogenesis in ischemic mouse brain, and further improved neurobehavioral outcomes. Our mechanistic study further showed that microRNA-126 mediated angiogenesis through directly inhibiting its target PTPN9 and activating AKT and ERK signaling pathways.

中文翻译：

---

MicroRNA-126 调节局灶性脑缺血小鼠模型中的血管生成和神经发生


研究表明 microRNA-126 在促进血管生成中发挥着关键作用。然而，其对缺血性中风后血管生成的影响尚不清楚。在这里，我们探讨了 microRNA-126-3p 和 microRNA-126-5p 对脑缺血后血管生成和神经发生的影响。我们证明，与乱序 miRNA 对照相比，microRNA (miRNA)-126-3p 和 microRNA-126-5p 均增加了人脐静脉内皮细胞 (HUVEC) 的增殖、迁移和管形成 (p < 0.05)。通过慢病毒将microRNA-126转移到小鼠大脑中动脉闭塞模型中，我们发现microRNA-126过表达增加了CD31/BrdU（5-溴-2'-脱氧尿苷阳性）增殖内皮细胞和DCX/BrdU神经母细胞的数量。与对照小鼠相比，缺血小鼠大脑的神经行为结果得到改善（p < 0.05），脑萎缩体积减少（p < 0.05）。 Western blot 结果显示，慢病毒-microRNA-126 治疗组中 AKT 和 ERK 信号通路被激活 (p < 0.05)。 PCR 和蛋白质印迹结果均表明，慢病毒-microRNA-126 治疗组的酪氨酸蛋白磷酸酶非受体 9 (PTPN9) 有所减少 (p < 0.05)。双荧光素酶基因报告基因检测还表明，它是缺血脑中 microRNA-126-3p 和 microRNA-126-5p 的直接靶标。我们证明 microRNA-126-3p 和 microRNA-126-5p 促进缺血小鼠大脑中的血管生成和神经发生，并进一步改善神经行为结果。我们的机制研究进一步表明，microRNA-126通过直接抑制其靶标PTPN9并激活AKT和ERK信号通路来介导血管生成。