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Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494

Cerebral stroke is a leading cause of death and permanent disability. The current therapeutic outcome of ischemic stroke (>85% of all strokes) is very poor, thus novel therapeutic drug is urgently needed. In vitro cell model of ischemia was established by oxygen-glucose deprivation (OGD) and in v...

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Autores principales: Song, Shiqing, Lin, Faliang, Zhu, Pengyan, Wu, Changyan, Zhao, Shuling, Han, Qiao, Li, Xiaomei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589225/
https://www.ncbi.nlm.nih.gov/pubmed/28880896
http://dx.doi.org/10.1371/journal.pone.0184348
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author Song, Shiqing
Lin, Faliang
Zhu, Pengyan
Wu, Changyan
Zhao, Shuling
Han, Qiao
Li, Xiaomei
author_facet Song, Shiqing
Lin, Faliang
Zhu, Pengyan
Wu, Changyan
Zhao, Shuling
Han, Qiao
Li, Xiaomei
author_sort Song, Shiqing
collection PubMed
description Cerebral stroke is a leading cause of death and permanent disability. The current therapeutic outcome of ischemic stroke (>85% of all strokes) is very poor, thus novel therapeutic drug is urgently needed. In vitro cell model of ischemia was established by oxygen-glucose deprivation (OGD) and in vivo animal model of ischemia was established by middle cerebral artery occlusion (MCAO). The effects of Spatholobus suberctus Dunn extract (SSCE) on OGD-induced cell injury, MCAO-induced neural injury and miR-494 level were all evaluated. The possible target genes were virtually screened utilizing bioinformatics and verified by luciferase assay. Subsequently, the effects of abnormally expressed miR-494 on OGD-induced cell injury and target gene expression were determined. Additionally, whether SSCE affected target gene expression through modulation of miR-494 was studied. Finally, the effects of aberrantly expressed Sox8 on OGD-induced injury and signaling pathways were estimated. SSCE reduced OGD-induced cell injury and ameliorated MCAO-induced neuronal injury, along with down-regulation of miR-494. Then, OGD-induced cell injury was increased by miR-494 overexpression but decreased by miR-494 silence. Sox8 was a target gene of miR-494, and SSCE could up-regulate Sox8 expression via down-regulating miR-494. Afterwards, OGD-induced cell injury was proved to be increased by Sox8 inhibition but reduced by Sox8 overexpression. Finally, OGD-induced inhibition of PI3K/AKT/mTOR and MAPK pathways was further inhibited by Sox8 silence but activated by Sox8 overexpression. SSCE ameliorates ischemia-induced injury both in vitro and in vivo by miR-494-mediated modulation of Sox8, involving activations of PI3K/AKT/mTOR and MAPK pathways.
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spelling pubmed-55892252017-09-15 Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494 Song, Shiqing Lin, Faliang Zhu, Pengyan Wu, Changyan Zhao, Shuling Han, Qiao Li, Xiaomei PLoS One Research Article Cerebral stroke is a leading cause of death and permanent disability. The current therapeutic outcome of ischemic stroke (>85% of all strokes) is very poor, thus novel therapeutic drug is urgently needed. In vitro cell model of ischemia was established by oxygen-glucose deprivation (OGD) and in vivo animal model of ischemia was established by middle cerebral artery occlusion (MCAO). The effects of Spatholobus suberctus Dunn extract (SSCE) on OGD-induced cell injury, MCAO-induced neural injury and miR-494 level were all evaluated. The possible target genes were virtually screened utilizing bioinformatics and verified by luciferase assay. Subsequently, the effects of abnormally expressed miR-494 on OGD-induced cell injury and target gene expression were determined. Additionally, whether SSCE affected target gene expression through modulation of miR-494 was studied. Finally, the effects of aberrantly expressed Sox8 on OGD-induced injury and signaling pathways were estimated. SSCE reduced OGD-induced cell injury and ameliorated MCAO-induced neuronal injury, along with down-regulation of miR-494. Then, OGD-induced cell injury was increased by miR-494 overexpression but decreased by miR-494 silence. Sox8 was a target gene of miR-494, and SSCE could up-regulate Sox8 expression via down-regulating miR-494. Afterwards, OGD-induced cell injury was proved to be increased by Sox8 inhibition but reduced by Sox8 overexpression. Finally, OGD-induced inhibition of PI3K/AKT/mTOR and MAPK pathways was further inhibited by Sox8 silence but activated by Sox8 overexpression. SSCE ameliorates ischemia-induced injury both in vitro and in vivo by miR-494-mediated modulation of Sox8, involving activations of PI3K/AKT/mTOR and MAPK pathways. Public Library of Science 2017-09-07 /pmc/articles/PMC5589225/ /pubmed/28880896 http://dx.doi.org/10.1371/journal.pone.0184348 Text en © 2017 Song et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Song, Shiqing
Lin, Faliang
Zhu, Pengyan
Wu, Changyan
Zhao, Shuling
Han, Qiao
Li, Xiaomei
Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494
title Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494
title_full Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494
title_fullStr Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494
title_full_unstemmed Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494
title_short Extract of Spatholobus suberctus Dunn ameliorates ischemia-induced injury by targeting miR-494
title_sort extract of spatholobus suberctus dunn ameliorates ischemia-induced injury by targeting mir-494
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589225/
https://www.ncbi.nlm.nih.gov/pubmed/28880896
http://dx.doi.org/10.1371/journal.pone.0184348
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