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Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke
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 R...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594728/ https://www.ncbi.nlm.nih.gov/pubmed/31167620 http://dx.doi.org/10.1161/STROKEAHA.118.023376 |
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author | Deng, Yiming Chen, Duanduan Wang, Luyao Gao, Feng Jin, Bo Lv, Hong Zhang, Guojun Sun, Xuan Liu, Lian Mo, Dapeng Ma, Ning Song, Ligang Huo, Xiaochuan Yan, Tianyi Miao, Zhongrong |
author_facet | Deng, Yiming Chen, Duanduan Wang, Luyao Gao, Feng Jin, Bo Lv, Hong Zhang, Guojun Sun, Xuan Liu, Lian Mo, Dapeng Ma, Ning Song, Ligang Huo, Xiaochuan Yan, Tianyi Miao, Zhongrong |
author_sort | Deng, Yiming |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6594728 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-65947282019-07-22 Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke Deng, Yiming Chen, Duanduan Wang, Luyao Gao, Feng Jin, Bo Lv, Hong Zhang, Guojun Sun, Xuan Liu, Lian Mo, Dapeng Ma, Ning Song, Ligang Huo, Xiaochuan Yan, Tianyi Miao, Zhongrong Stroke Original Contributions 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. Lippincott Williams & Wilkins 2019-07 2019-06-07 /pmc/articles/PMC6594728/ /pubmed/31167620 http://dx.doi.org/10.1161/STROKEAHA.118.023376 Text en © 2019 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made. |
spellingShingle | Original Contributions Deng, Yiming Chen, Duanduan Wang, Luyao Gao, Feng Jin, Bo Lv, Hong Zhang, Guojun Sun, Xuan Liu, Lian Mo, Dapeng Ma, Ning Song, Ligang Huo, Xiaochuan Yan, Tianyi Miao, Zhongrong Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke |
title | Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke |
title_full | Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke |
title_fullStr | Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke |
title_full_unstemmed | Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke |
title_short | Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke |
title_sort | silencing of long noncoding rna nespas aggravates microglial cell death and neuroinflammation in ischemic stroke |
topic | Original Contributions |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594728/ https://www.ncbi.nlm.nih.gov/pubmed/31167620 http://dx.doi.org/10.1161/STROKEAHA.118.023376 |
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