Cargando…
MiR-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting PTEN
INTRODUCTION: Ischemic stroke (IS) is a common and severe neurological disorder and is associated with high rates of mortality and morbidity. Inflammatory reaction in astrocytes is one of the important pathological factors of stroke. Improved understanding of the underlying molecular mechanisms shou...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
KeAi Publishing
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488463/ https://www.ncbi.nlm.nih.gov/pubmed/34632168 http://dx.doi.org/10.1016/j.ncrna.2021.09.002 |
_version_ | 1784578174281056256 |
---|---|
author | Guan, Xiaoxiang Zhang, Yiwei Gareev, Ilgiz Beylerli, Ozal Li, Xinyuan Lu, Guitian Lv, Lin Hai, Xin |
author_facet | Guan, Xiaoxiang Zhang, Yiwei Gareev, Ilgiz Beylerli, Ozal Li, Xinyuan Lu, Guitian Lv, Lin Hai, Xin |
author_sort | Guan, Xiaoxiang |
collection | PubMed |
description | INTRODUCTION: Ischemic stroke (IS) is a common and severe neurological disorder and is associated with high rates of mortality and morbidity. Inflammatory reaction in astrocytes is one of the important pathological factors of stroke. Improved understanding of the underlying molecular mechanisms should aid better treatment of the disease. This study aimed to test our hypothesis that a miR-499a played an important role in the inflammatory response in astrocytes induced by IS targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). METHODS: This study was comprised of two models: oxygen-glucose deprivation (OGD) and reoxygenation model. Quantitative real-time PCR (qRT-PCR) and Western blot were used to examine gene expression levels, and MTT assay analysis were used to examine cell states. The relationships between miR-499a and PTEN were confirmed by luciferase reporter assay. RESULTS: MiR-499a was robustly downregulated with OGD induced injury in astrocytes. Forced transient expression of miR-499a in OGD astrocytes nearly completely reversed the inflammatory response. Knockdown of miR-499a by its specific inhibitor in healthy astrocytes induced the inflammatory response resembling those produced by OGD. On the other hand, PTEN was markedly upregulated in OGD astrocytes, which was reciprocal to the expression of miR-499a. PTEN was experimentally validated as a direct target gene for miR-499a. Overexpression of PTEN was able to induce an inflammatory response of astrocytes. Moreover, PTEN siRNA counteracted the inflammatory response induced by OGD. CONCLUSIONS: Taken together, our findings indicate miR-499a as an important factor to prevent inflammatory response and suggest miR-499a as a new molecule for the treatment of IS. The present study also demonstrated the relationship between miR-499a and PTEN, with PTEN as a downstream signaling mediator of miR-499a in the inflammatory response of astrocytes induced by IS. |
format | Online Article Text |
id | pubmed-8488463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | KeAi Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-84884632021-10-08 MiR-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting PTEN Guan, Xiaoxiang Zhang, Yiwei Gareev, Ilgiz Beylerli, Ozal Li, Xinyuan Lu, Guitian Lv, Lin Hai, Xin Noncoding RNA Res Article INTRODUCTION: Ischemic stroke (IS) is a common and severe neurological disorder and is associated with high rates of mortality and morbidity. Inflammatory reaction in astrocytes is one of the important pathological factors of stroke. Improved understanding of the underlying molecular mechanisms should aid better treatment of the disease. This study aimed to test our hypothesis that a miR-499a played an important role in the inflammatory response in astrocytes induced by IS targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). METHODS: This study was comprised of two models: oxygen-glucose deprivation (OGD) and reoxygenation model. Quantitative real-time PCR (qRT-PCR) and Western blot were used to examine gene expression levels, and MTT assay analysis were used to examine cell states. The relationships between miR-499a and PTEN were confirmed by luciferase reporter assay. RESULTS: MiR-499a was robustly downregulated with OGD induced injury in astrocytes. Forced transient expression of miR-499a in OGD astrocytes nearly completely reversed the inflammatory response. Knockdown of miR-499a by its specific inhibitor in healthy astrocytes induced the inflammatory response resembling those produced by OGD. On the other hand, PTEN was markedly upregulated in OGD astrocytes, which was reciprocal to the expression of miR-499a. PTEN was experimentally validated as a direct target gene for miR-499a. Overexpression of PTEN was able to induce an inflammatory response of astrocytes. Moreover, PTEN siRNA counteracted the inflammatory response induced by OGD. CONCLUSIONS: Taken together, our findings indicate miR-499a as an important factor to prevent inflammatory response and suggest miR-499a as a new molecule for the treatment of IS. The present study also demonstrated the relationship between miR-499a and PTEN, with PTEN as a downstream signaling mediator of miR-499a in the inflammatory response of astrocytes induced by IS. KeAi Publishing 2021-09-28 /pmc/articles/PMC8488463/ /pubmed/34632168 http://dx.doi.org/10.1016/j.ncrna.2021.09.002 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Guan, Xiaoxiang Zhang, Yiwei Gareev, Ilgiz Beylerli, Ozal Li, Xinyuan Lu, Guitian Lv, Lin Hai, Xin MiR-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting PTEN |
title | MiR-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting PTEN |
title_full | MiR-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting PTEN |
title_fullStr | MiR-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting PTEN |
title_full_unstemmed | MiR-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting PTEN |
title_short | MiR-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting PTEN |
title_sort | mir-499a prevents astrocytes mediated inflammation in ischemic stroke by targeting pten |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488463/ https://www.ncbi.nlm.nih.gov/pubmed/34632168 http://dx.doi.org/10.1016/j.ncrna.2021.09.002 |
work_keys_str_mv | AT guanxiaoxiang mir499apreventsastrocytesmediatedinflammationinischemicstrokebytargetingpten AT zhangyiwei mir499apreventsastrocytesmediatedinflammationinischemicstrokebytargetingpten AT gareevilgiz mir499apreventsastrocytesmediatedinflammationinischemicstrokebytargetingpten AT beylerliozal mir499apreventsastrocytesmediatedinflammationinischemicstrokebytargetingpten AT lixinyuan mir499apreventsastrocytesmediatedinflammationinischemicstrokebytargetingpten AT luguitian mir499apreventsastrocytesmediatedinflammationinischemicstrokebytargetingpten AT lvlin mir499apreventsastrocytesmediatedinflammationinischemicstrokebytargetingpten AT haixin mir499apreventsastrocytesmediatedinflammationinischemicstrokebytargetingpten |