MicroRNA-126 Regulates Angiogenesis and Neurogenesis in a Mouse Model of Focal Cerebral Ischemia

作者：Meijie Qu, Jiaji Pan, Liping Wang, Panting Zhou, Yaying Song, Shuhong Wang, Lu Jiang, Jieli Geng, Zhijun Zhang, Yongting Wang, Yaohui Tang, Guo‐Yuan Yang · 发表于：Molecular Therapy — Nucleic Acids · 年份：2019 · DOI：10.1016/j.omtn.2019.02.002 · 被引用次数：78 · 研究领域：Protein Tyrosine Phosphatases、Circular RNAs in diseases、Moyamoya disease diagnosis and treatment

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 PTPN9 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 isc...