Downregulation of miR-491-5p promotes neovascularization after traumatic brain injury  

作　　者：Wei Tang Zong-Duo Guo Wei-Na Chai Dong-Lin Du Xiao-Min Yang Lang Cao Hong Chen Chao Zhou Chong-Jie Cheng Xiao-Chuan Sun Zhi-Jian Huang Jian-Jun Zhong 

机构地区：[1]Department of Neurosurgery,First Affiliated Hospital of Chongqing Medical University,Chongqing,China [2]Department of Ophthalmology,First Affiliated Hospital of Chongqing Medical University,Chongqing,China

出　　处：《Neural Regeneration Research》2022年第3期577-586,共10页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82071397 (to XCS),82071332 (to ZDG);the Youth Fund of the National Natural Science Foundation of China,No.81801230 (to JJZ);the Excellent Scientific Research Talents Fund of the First Affiliated Hospital of Chongqing Medical University,China (to JJZ)。

摘　　要：Micro RNA-491-5 p(miR-491-5 p) plays an important role in regulating cell proliferation and migration;however,the effect of miR-491-5 p on neovascularization after traumatic brain injury remains poorly understood.In this study,a controlled cortical injury model in C57 BL/6 mice and an oxygen-glucose deprivation model in microvascular endothelial cells derived from mouse brain were established to simulate traumatic brain injury in vivo and in vitro,respectively.In the in vivo model,quantitative real-time-polymerase chain reaction results showed that the expression of miR-491-5 p increased or decreased following the intracerebroventricular injection of an miR-491-5 p agomir or antagomir,respectively,and the expression of miR-491-5 p decreased slightly after traumatic brain injury.To detect the neuroprotective effects of miR-491-p,neurological severity scores,Morris water maze test,laser speckle techniques,and immunofluorescence staining were assessed,and the results revealed that miR-491-5 p downregulation alleviated neurological dysfunction,promoted the recovery of regional cerebral blood flow,increased the number of lectin-stained microvessels,and increased the survival of neurons after traumatic brain injury.During the in vitro experiments,the potential mechanism of miR-491-5 p on neovascularization was explored through quantitative real-time-polymerase chain reaction,which showed that miR-491-5 p expression increased or decreased in brain microvascular endothelial cells after transfection with an miR-491-5 p mimic or inhibitor,respectively.Dual-luciferase reporter and western blot assays verified that metallothionein-2 was a target gene for miR-491-5 p.Cell counting kit 8(CCK-8) assay,flow cytometry,and 2′,7′-dichlorofluorescein diacetate(DCFH-DA) assay results confirmed that the downregulation of miR-491-5 p increased brain microvascular endothelial cell viability,reduced cell apoptosis,and alleviated oxidative stress under oxygen-glucose deprivation conditions.Cell scratch assay,Transwell assay,tube forma

关 键 词：brain injury cell migration cell proliferation endothelial cell hypoxia-inducible factor-1 alpha metallothionein 2 microRNA NEOVASCULARIZATION neurons vascular endothelial growth factor 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学]