Cargando…
Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats
Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to imp...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021718/ https://www.ncbi.nlm.nih.gov/pubmed/33833666 http://dx.doi.org/10.3389/fnmol.2021.613887 |
_version_ | 1783674791743455232 |
---|---|
author | Yang, Huajun Zhang, Yifan Chen, Hongqun Zhu, Yingwu Li, Yuan Ouyang, Fu Chu, Lan Liu, Daishun |
author_facet | Yang, Huajun Zhang, Yifan Chen, Hongqun Zhu, Yingwu Li, Yuan Ouyang, Fu Chu, Lan Liu, Daishun |
author_sort | Yang, Huajun |
collection | PubMed |
description | Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke. |
format | Online Article Text |
id | pubmed-8021718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80217182021-04-07 Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats Yang, Huajun Zhang, Yifan Chen, Hongqun Zhu, Yingwu Li, Yuan Ouyang, Fu Chu, Lan Liu, Daishun Front Mol Neurosci Neuroscience Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke. Frontiers Media S.A. 2021-03-23 /pmc/articles/PMC8021718/ /pubmed/33833666 http://dx.doi.org/10.3389/fnmol.2021.613887 Text en Copyright © 2021 Yang, Zhang, Chen, Zhu, Li, Ouyang, Chu and Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Yang, Huajun Zhang, Yifan Chen, Hongqun Zhu, Yingwu Li, Yuan Ouyang, Fu Chu, Lan Liu, Daishun Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats |
title | Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats |
title_full | Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats |
title_fullStr | Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats |
title_full_unstemmed | Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats |
title_short | Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats |
title_sort | mir-184 contributes to brain injury through targeting ppap2b following ischemic stroke in male rats |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021718/ https://www.ncbi.nlm.nih.gov/pubmed/33833666 http://dx.doi.org/10.3389/fnmol.2021.613887 |
work_keys_str_mv | AT yanghuajun mir184contributestobraininjurythroughtargetingppap2bfollowingischemicstrokeinmalerats AT zhangyifan mir184contributestobraininjurythroughtargetingppap2bfollowingischemicstrokeinmalerats AT chenhongqun mir184contributestobraininjurythroughtargetingppap2bfollowingischemicstrokeinmalerats AT zhuyingwu mir184contributestobraininjurythroughtargetingppap2bfollowingischemicstrokeinmalerats AT liyuan mir184contributestobraininjurythroughtargetingppap2bfollowingischemicstrokeinmalerats AT ouyangfu mir184contributestobraininjurythroughtargetingppap2bfollowingischemicstrokeinmalerats AT chulan mir184contributestobraininjurythroughtargetingppap2bfollowingischemicstrokeinmalerats AT liudaishun mir184contributestobraininjurythroughtargetingppap2bfollowingischemicstrokeinmalerats |