Essential role of MALAT1 in reducing traumatic brain injury

作者全名:"Wu, Na; Cheng, Chong-Jie; Zhong, Jian-Jun; He, Jun-Chi; Zhang, Zhao-Si; Wang, Zhi-Gang; Sun, Xiao-Chuan; Liu, Han"

作者地址:"[Wu, Na; Cheng, Chong-Jie; Zhong, Jian-Jun; He, Jun-Chi; Zhang, Zhao-Si; Wang, Zhi-Gang; Sun, Xiao-Chuan; Liu, Han] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Chongqing, Peoples R China; [Liu, Han] Shandong Univ, Dept Neurosurg, Qilu Hosp, Qingdao Campus, Qingdao, Shandong, Peoples R China"

通信作者:"Liu, H (通讯作者),Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Chongqing, Peoples R China.; Liu, H (通讯作者),Shandong Univ, Dept Neurosurg, Qilu Hosp, Qingdao Campus, Qingdao, Shandong, Peoples R China."

来源:NEURAL REGENERATION RESEARCH

ESI学科分类:NEUROSCIENCE & BEHAVIOR

WOS号:WOS:000766445300033

JCR分区:Q2

影响因子:6.1

年份:2022

卷号:17

期号:8

开始页:1776

结束页:1784

文献类型:Article

关键词:angiogenesis; controlled cortical impact; EZH2; Jagged-1; LncRNA; MALAT1; NOTCH1; oxygen-glucose deprivation; traumatic brain injury; vascular remodeling

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."

基金机构:"National Natural Science Foundation of China [81571159, 81601072]; Natural Science Foundation of Chongqing, China [cstc2019jcyj-msxmX0830]"

基金资助正文:"The study was 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); and the Natural Science Foundation of Chongqing, China, No. cstc2019jcyj-msxmX0830 (to CJC)."