Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (8): 1776-1784.doi: 10.4103/1673-5374.332156

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Essential role of MALAT1 in reducing traumatic brain injury

Na Wu1, #, Chong-Jie Cheng1, #, Jian-Jun Zhong1, Jun-Chi He1, Zhao-Si Zhang1, Zhi-Gang Wang1, Xiao-Chuan Sun1, Han Liu1, 2, *   

  1. 1Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Department of Neurosurgery, Qilu Hospital of Shandong University (Qingdao Campus), Qingdao, Shandong Province, China
  • Online:2022-08-15 Published:2022-01-22
  • Contact: Han Liu, PhD, 1019266517@qq.com.
  • Supported by:
    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).

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Abstract: 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.

Key words: angiogenesis, controlled cortical impact, EZH2, Jagged-1, LncRNA, MALAT1, NOTCH1, oxygen-glucose deprivation, traumatic brain injury, vascular remodeling