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

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.

journal_name

Stroke

journal_title

Stroke

authors

Deng Y,Chen D,Wang L,Gao F,Jin B,Lv H,Zhang G,Sun X,Liu L,Mo D,Ma N,Song L,Huo X,Yan T,Miao Z

doi

10.1161/STROKEAHA.118.023376

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

1850-1858

issue

7

eissn

0039-2499

issn

1524-4628

journal_volume

50

pub_type

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