Essential role of MALAT1 in reducing traumatic brain injury  

作　　者：Na Wu Chong-Jie Cheng Jian-Jun Zhong Jun-Chi He Zhao-Si Zhang Zhi-Gang Wang Xiao-Chuan Sun Han Liu 

机构地区：[1]Department of Neurosurgery,the First Affiliated Hospital of Chongqing Medical University,Chongqing,China [2]Department of Neurosurgery,Qilu Hospital of Shandong University(Qingdao Campus),Qingdao,Shandong Province,China

出　　处：《Neural Regeneration Research》2022年第8期1776-1784,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81571159(to XCS);the National Natural Science Foundation of China(Youth Program),No.81601072(to CJC);the Natural Science Foundation of Chongqing,China,No.cstc2019jcyj-msxmX0830(to CJC).

摘　　要：As a highly evolutionary conserved long non-coding RNA,metastasis associated lung adenocarcinoma transcript 1(MALAT1)was first demonstrated to be related to lung tumor metastasis by promoting angiogenesis.To investigate the role of MALAT1 in traumatic brain injury,we established mouse models of controlled cortical impact and cell models of oxygen-glucose deprivation to mimic traumatic brain injury in vitro and in vivo.The results revealed that MALAT1 silencing in vitro inhibited endothelial cell viability and tube formation but increased migration.In MALAT1-deficient mice,endothelial cell proliferation in the injured cortex,functional vessel density and cerebral blood flow were reduced.Bioinformatic analyses and RNA pull-down assays validated enhancer of zeste homolog 2(EZH2)as a downstream factor of MALAT1 in endothelial cells.Jagged-1,the Notch homolog 1(NOTCH1)agonist,reversed the MALAT1 deficiency-mediated impairment of angiogenesis.Taken together,our results suggest that MALAT1 controls the key processes of angiogenesis following traumatic brain injury in an EZH2/NOTCH1-dependent manner.

关 键 词：ANGIOGENESIS controlled cortical impact EZH2 JAGGED-1 LncRNA MALAT1 NOTCH1 oxygen-glucose deprivation traumatic brain injury vascular remodeling 

分 类 号：R651.15[医药卫生—外科学]