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

Yiming Deng, Duanduan Chen, Luyao Wang, Feng Gao, Bo Jin, Hong Lv, Guojun Zhang, Xuan Sun, Lian Liu, Dapeng Mo, Ning Ma, Ligang Song, Xiaochuan Huo, Tianyi Yan*, Zhongrong Miao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1850-1858
Number of pages9
JournalStroke
Volume50
Issue number7
DOIs
Publication statusPublished - 1 Jul 2019

Keywords

  • TAK1
  • cell death
  • lncRNA
  • neuroinflammation
  • stroke

Fingerprint

Dive into the research topics of 'Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke'. Together they form a unique fingerprint.

Cite this