Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke

Author:

Deng Yiming123,Chen Duanduan45,Wang Luyao6,Gao Feng123,Jin Bo7,Lv Hong7,Zhang Guojun7,Sun Xuan123,Liu Lian123,Mo Dapeng123,Ma Ning123,Song Ligang123,Huo Xiaochuan123,Yan Tianyi45,Miao Zhongrong123

Affiliation:

1. Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, China (Y.D., F.G., X.S., L.L., D.M., N.M., L.S., X.H., Z.M.)

2. China National Clinical Research Center for Neurological Diseases (Y.D., F.G., X.S., L.L., D.M., N.M., L.S., X.H., Z.M.)

3. Center of Stroke, Beijing Institute for Brain Disorders, China (Y.D., F.G., X.S., L.L., D.M., N.M., L.S., X.H., Z.M.)

4. From the School of Life Science (D.C., T.Y.), Beijing Institute of Technology, China

5. Key Laboratory of Convergence Medical Engineering System and Healthcare Technology, Ministry of Industry and Information Technology (D.C., T.Y.), Beijing Institute of Technology, China

6. Intelligent Robotics Institute, School of Mechatronical Engineering (L.W.), Beijing Institute of Technology, China

7. Department of Clinical Laboratory, Peking University First Hospital, Beijing, China (B.J., H.L., G.Z.).

Abstract

Background and Purpose— Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown. In the current study, for the first time, we investigated the role of long noncoding RNA Nespas in ischemic stroke. Methods— We used in vivo models of middle cerebral artery occlusion and in vitro models of oxygen-glucose deprivation to illustrate the effect of long noncoding RNA Nespas on ischemic stroke. Results— We found expression of Nespas was significantly increased in ischemic cerebral tissues and oxygen-glucose deprivation–treated BV2 cells in a time-dependent manner. Silencing of Nespas aggravated middle cerebral artery occlusion operation–induced IR injury and cell death. In addition, proinflammatory cytokine production and NF-κB (nuclear factor-κB) signaling activation were inhibited by Nespas overexpression. TAK1 (transforming growth factor-β–activated kinase 1) was found to directly interact with Nespas, and TAK1 activation was significantly suppressed by Nespas. At last, we found Nespas-inhibited TRIM8 (tripartite motif 8)-induced K63-linked polyubiquitination of TAK1. Conclusions— We showed that Nespas played anti-inflammatory and antiapoptotic roles in cultured microglial cells after oxygen-glucose deprivation stimulation and in mice after ischemic stroke by inhibiting TRIM8-related K63-linked polyubiquitination of TAK1.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Advanced and Specialised Nursing,Cardiology and Cardiovascular Medicine,Clinical Neurology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3