MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway

Xiaoli Ren,1 Zhiyun Wang,1 Congfang Guo2 1Department of Neurology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China; 2Department of Emergency, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of ChinaCorrespondence: Zhiyun WangDepartme...

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Autores principales: Ren X, Wang Z, Guo C
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spelling oai:doaj.org-article:565fa57f0eb44d1fb1bb84cf04a97a302021-12-02T14:32:45ZMiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway1178-2021https://doaj.org/article/565fa57f0eb44d1fb1bb84cf04a97a302021-04-01T00:00:00Zhttps://www.dovepress.com/mir-195-5p-ameliorates-cerebral-ischemia-reperfusion-injury-by-regulat-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Xiaoli Ren,1 Zhiyun Wang,1 Congfang Guo2 1Department of Neurology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China; 2Department of Emergency, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of ChinaCorrespondence: Zhiyun WangDepartment of Neurology, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People’s Republic of ChinaEmail ZhiyunWanghospital@163.comBackground: MiR-195-5p has been shown to play crucial roles in tumor inhibition, but its biological functions in cerebral ischemia-reperfusion (I/R) injury are unclear.Methods: To mimic cerebral I/R injury, mice were induced by transient middle cerebral artery occlusion (MCAO). Human brain microvascular endothelial cells (HBMVECs) were treated with oxygen-glucose deprivation (OGD) to mimic I/R injury in vitro. The expression of miR-195-5p and PTEN was detected by qRT-PCR or Western blot. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometer. Cell death was detected using specific lactate dehydrogenase (LDH) cytotoxicity kit. Infarct volume in mice brains was evaluated by TTC staining. Histopathological analysis was performed by HE staining and TUNEL staining. The interaction between miR-195-5p and PTEN was determined by TargetScan and luciferase reporter assay.Results: MiR-195-5p was significantly downregulated and PTEN was upregulated during cerebral I/R injury both in vitro and in vivo. Overexpression of miR-195-5p efficiently enhanced cell viability, while reduced LDH release and apoptotic rate of OGD-treated HBMVECs in vitro. MiR-195-5p could negatively regulate the expression of PTEN by directly binding to its 3′-UTR. Overexpression of PTEN obviously attenuated the protective effect of miR-195-5p mimics on cell viability, LDH release and apoptosis in OGD-treated HBMVECs. Meanwhile, overexpression of miR-195-5p increased the expression levels of p-AKT in OGD-treated HBMVECs, while this effect was reversed by overexpression of PTEN. Moreover, overexpression of miR-195-5p efficiently ameliorated brain injury of mice after MCAO treatment in vivo.Conclusion: Overexpression of miR-195-5p ameliorated cerebral I/R injury by regulating the PTEN-AKT signaling pathway, providing a potential therapeutic target for cerebral I/R injury.Keywords: cerebral I/R injury, miR-195-5p, PTEN, AKT signaling pathwayRen XWang ZGuo CDove Medical Pressarticlecerebral i/r injurymir-195-5pptenakt signaling pathwayNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 1231-1242 (2021)
institution DOAJ
collection DOAJ
language EN
topic cerebral i/r injury
mir-195-5p
pten
akt signaling pathway
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle cerebral i/r injury
mir-195-5p
pten
akt signaling pathway
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Ren X
Wang Z
Guo C
MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway
description Xiaoli Ren,1 Zhiyun Wang,1 Congfang Guo2 1Department of Neurology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China; 2Department of Emergency, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of ChinaCorrespondence: Zhiyun WangDepartment of Neurology, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People’s Republic of ChinaEmail ZhiyunWanghospital@163.comBackground: MiR-195-5p has been shown to play crucial roles in tumor inhibition, but its biological functions in cerebral ischemia-reperfusion (I/R) injury are unclear.Methods: To mimic cerebral I/R injury, mice were induced by transient middle cerebral artery occlusion (MCAO). Human brain microvascular endothelial cells (HBMVECs) were treated with oxygen-glucose deprivation (OGD) to mimic I/R injury in vitro. The expression of miR-195-5p and PTEN was detected by qRT-PCR or Western blot. Cell viability was evaluated by CCK-8 assay. Cell apoptosis was detected by flow cytometer. Cell death was detected using specific lactate dehydrogenase (LDH) cytotoxicity kit. Infarct volume in mice brains was evaluated by TTC staining. Histopathological analysis was performed by HE staining and TUNEL staining. The interaction between miR-195-5p and PTEN was determined by TargetScan and luciferase reporter assay.Results: MiR-195-5p was significantly downregulated and PTEN was upregulated during cerebral I/R injury both in vitro and in vivo. Overexpression of miR-195-5p efficiently enhanced cell viability, while reduced LDH release and apoptotic rate of OGD-treated HBMVECs in vitro. MiR-195-5p could negatively regulate the expression of PTEN by directly binding to its 3′-UTR. Overexpression of PTEN obviously attenuated the protective effect of miR-195-5p mimics on cell viability, LDH release and apoptosis in OGD-treated HBMVECs. Meanwhile, overexpression of miR-195-5p increased the expression levels of p-AKT in OGD-treated HBMVECs, while this effect was reversed by overexpression of PTEN. Moreover, overexpression of miR-195-5p efficiently ameliorated brain injury of mice after MCAO treatment in vivo.Conclusion: Overexpression of miR-195-5p ameliorated cerebral I/R injury by regulating the PTEN-AKT signaling pathway, providing a potential therapeutic target for cerebral I/R injury.Keywords: cerebral I/R injury, miR-195-5p, PTEN, AKT signaling pathway
format article
author Ren X
Wang Z
Guo C
author_facet Ren X
Wang Z
Guo C
author_sort Ren X
title MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway
title_short MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway
title_full MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway
title_fullStr MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway
title_full_unstemmed MiR-195-5p Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulating the PTEN-AKT Signaling Pathway
title_sort mir-195-5p ameliorates cerebral ischemia-reperfusion injury by regulating the pten-akt signaling pathway
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/565fa57f0eb44d1fb1bb84cf04a97a30
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AT wangz mir1955pamelioratescerebralischemiareperfusioninjurybyregulatingtheptenaktsignalingpathway
AT guoc mir1955pamelioratescerebralischemiareperfusioninjurybyregulatingtheptenaktsignalingpathway
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