Downregulation of the Long Non-Coding RNA Meg3 Promotes Angiogenesis After Ischemic Brain Injury by Activating Notch Signaling

被引：188

作者：

Liu, Juan ^{[1
]}

Li, Qing ^{[2
]}

Zhang, Kun-shan ^{[3
]}

Hu, Bin ^{[2
]}

Niu, Xin ^{[2
]}

Zhou, Shu-min ^{[2
]}

Li, Si-guang ^{[3
]}

Luo, Yu-ping ^{[3
]}

Wang, Yang ^{[2
]}

Deng, Zhi-feng ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Neurosurg, Affiliated Peoples Hosp 6, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Inst Microsurg Extrem, Affiliated Peoples Hosp 6, Shanghai, Peoples R China

[3] Tongji Univ, Tongji Hosp, Stem Cell Translat Res Ctr, Sch Med, Shanghai, Peoples R China

来源：

MOLECULAR NEUROBIOLOGY | 2017年 / 54卷 / 10期

基金：

中国国家自然科学基金;

关键词：

LncRNAs; MEG3; Ischemic stroke; Angiogenesis; Notch pathway; MARROW STROMAL CELLS; ENDOTHELIAL NOTCH1; EXPRESSION; DYSFUNCTION; MECHANISMS; RECOVERY; PATHWAY; TARGET;

D O I：

10.1007/s12035-016-0270-z

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Angiogenesis after ischemic brain injury contributes to the restoration of blood supply in the ischemic zone. Strategies to improve angiogenesis may facilitate the function recovery after stroke. Recent researches have demonstrated that dysfunction of long non-coding RNAs are associated with angiogenesis. We have previously reported that long non-coding RNAs (lncRNAs) are aberrantly expressed in ischemic stroke. However, little is known about long non-coding RNAs and theirs role in angiogenesis after stroke. In this study, we identified a rat lncRNAs, Meg3, and found that Meg3 was significantly decreased after ischemic stroke. Overexpression of Meg3 suppressed functional recovery and decreased capillary density after ischemic stroke. Downregulation of Meg3 ameliorated brain lesion and increased angiogenesis after ischemic stroke. Silencing of Meg3 resulted in a proangiogenic effect evidenced by increased endothelial cell migration, proliferation, sprouting, and tube formation. Mechanistically, we showed that Meg3 negatively regulated notch pathway both in vivo and in vitro. Inhibition of notch signaling in endothelial cells reversed the proangiogenic effect induced by Meg3 downregulation. This study revealed the function of Meg3 in ischemic stroke and elucidated its mechanism in angiogenesis after ischemic stroke.

引用

页码：8179 / 8190

页数：12

共 44 条

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