Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 490, Issue 3, Pages 700-706Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.06.104
Keywords
LncRNA MEG3; Cerebral infarction; NOX4; p53
Categories
Funding
- National Natural Science Foundation of China [81501065]
- Zhejiang Provincial Natural Science Foundation [LY16H090004]
- Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan [2016ZA115]
- Zhejiang Provincial Medical and Health Science and Technology Plan [2015KYA091]
Ask authors/readers for more resources
Objective: This study aimed to explore the mechanism of lncRNA MEG3 on angiogenesis after cerebral infarction (CI). Methods: The rat brain microvascular endothelial cells (RBMVECs) isolated from rat was used to establish CI model, which were treated with oxygen-glucose deprivation/reoxygenation (OGD/R). The genes mRNA and protein expression levels in RBMVECs were determined by the quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively. The flow cytometry was used to measured cell apoptosis and intracellular reactive oxygen species (ROS) generation. The RBMVECs activities was detected by MTT method. The RNA-immunoprecipitation (RIP) assay was used to detect the interaction between MEG3 and p53, and the relationship between p53 and NOX4 was proved by chromatin co-immunoprecipitation (chip) assay. Results: The results showed that OGD or OGD/R increased MEG3 and NOX4 expression, and there was positive correlation between MEG3 and NOX4 expression in RBMVECs. Next, knockdown of MEG3 indicated that inhibition of MEG3 was conducive to protect RBMVECs against OGD/R-induced apoptosis, with decreased NOX4 and p53 expression, further enhanced pro-angiogenic factors (HIF-1 alpha and VEGF) expression, and reduced intracellular ROS generation. And then the RIP and CHIP assay demonstrated that MEG3 could interacted with p53 and regulated its expression, and p53 exerted significant binding in the promoters for NOX4, suggesting that MEG3 regulated NOX4 expression via p53. At last, knockdown of NOX4 indicated that inhibition of NOX4 protected RBMVECs against OGD/R-induced apoptosis, with increased cell viability and pro-angiogenic factors expression, and reduced ROS generation. Conclusion: LncRNA MEG3 was an important regulator in OGD/R induced-RBMVECs apoptosis and the mechanism of MEG3 on angiogenesis after CI was reduced ROS by p53/NOX4 axis. (C) 2017 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available