MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE Pathway

Ischemic stroke is a debilitating central nervous disease linked to oxidative stress. Although miR-367-3p has been reported to be related to ischemic stroke, the direct evidence concerning oxidative stress remains elusive. Our study aimed to elucidate the mechanisms associated with oxidative stress...

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Main Authors: Qian He, Xingwen Tian, Yujie Zhang, Qiong Mu
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-05-01
Series:Journal of Physiological Investigation
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Online Access:https://journals.lww.com/jpi/fulltext/2025/05000/mir_367_3p_alleviates_oxidative_stress_injury_in.2.aspx
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author Qian He
Xingwen Tian
Yujie Zhang
Qiong Mu
author_facet Qian He
Xingwen Tian
Yujie Zhang
Qiong Mu
author_sort Qian He
collection DOAJ
description Ischemic stroke is a debilitating central nervous disease linked to oxidative stress. Although miR-367-3p has been reported to be related to ischemic stroke, the direct evidence concerning oxidative stress remains elusive. Our study aimed to elucidate the mechanisms associated with oxidative stress in ischemic stroke. Initially, we discovered that miR-367-3p was notably downregulated in SH-SY5Y cells induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Employing the in vitro ischemia/reperfusion injury model, we further demonstrated that overexpression of miR-367-3p alleviated OGD/R-induced apoptosis, inflammation, and oxidative stress, accompanied by the activation of the Keap1/Nrf2/ARE pathway. Mechanistically, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) was confirmed to be the target of miR-367-3p by dual-luciferase reporter assay. Moreover, the knockdown of NOX4 mimicked, while overexpression reversed the effects of miR-367-3p overexpression on OGD/R-induced oxidative stress injury and the impaired Keap1/Nrf2/ARE pathway. In conclusion, our findings indicate that miR-367-3p mitigates OGD/R-induced oxidative stress injury by activating the Keap1/Nrf2/ARE pathway through targeting NOX4.
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spelling doaj-art-3f9da336933c417ca5ce64e6ec26ea7b2025-08-20T03:16:26ZengWolters Kluwer Medknow PublicationsJournal of Physiological Investigation2950-63442950-63522025-05-0168314014910.4103/ejpi.EJPI-D-24-00103MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE PathwayQian HeXingwen TianYujie ZhangQiong MuIschemic stroke is a debilitating central nervous disease linked to oxidative stress. Although miR-367-3p has been reported to be related to ischemic stroke, the direct evidence concerning oxidative stress remains elusive. Our study aimed to elucidate the mechanisms associated with oxidative stress in ischemic stroke. Initially, we discovered that miR-367-3p was notably downregulated in SH-SY5Y cells induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Employing the in vitro ischemia/reperfusion injury model, we further demonstrated that overexpression of miR-367-3p alleviated OGD/R-induced apoptosis, inflammation, and oxidative stress, accompanied by the activation of the Keap1/Nrf2/ARE pathway. Mechanistically, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) was confirmed to be the target of miR-367-3p by dual-luciferase reporter assay. Moreover, the knockdown of NOX4 mimicked, while overexpression reversed the effects of miR-367-3p overexpression on OGD/R-induced oxidative stress injury and the impaired Keap1/Nrf2/ARE pathway. In conclusion, our findings indicate that miR-367-3p mitigates OGD/R-induced oxidative stress injury by activating the Keap1/Nrf2/ARE pathway through targeting NOX4.https://journals.lww.com/jpi/fulltext/2025/05000/mir_367_3p_alleviates_oxidative_stress_injury_in.2.aspxkeap1/nrf2/are pathwaymir-367-3pnicotinamide adenine dinucleotide phosphate oxidase 4oxygen-glucose deprivation/reoxygenationoxidative stress
spellingShingle Qian He
Xingwen Tian
Yujie Zhang
Qiong Mu
MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE Pathway
Journal of Physiological Investigation
keap1/nrf2/are pathway
mir-367-3p
nicotinamide adenine dinucleotide phosphate oxidase 4
oxygen-glucose deprivation/reoxygenation
oxidative stress
title MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE Pathway
title_full MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE Pathway
title_fullStr MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE Pathway
title_full_unstemmed MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE Pathway
title_short MiR-367-3p Alleviates Oxidative Stress Injury in the Ischemia/Reperfusion Injury Cell Model by Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4-mediated Keap1/Nrf2/ARE Pathway
title_sort mir 367 3p alleviates oxidative stress injury in the ischemia reperfusion injury cell model by targeting nicotinamide adenine dinucleotide phosphate oxidase 4 mediated keap1 nrf2 are pathway
topic keap1/nrf2/are pathway
mir-367-3p
nicotinamide adenine dinucleotide phosphate oxidase 4
oxygen-glucose deprivation/reoxygenation
oxidative stress
url https://journals.lww.com/jpi/fulltext/2025/05000/mir_367_3p_alleviates_oxidative_stress_injury_in.2.aspx
work_keys_str_mv AT qianhe mir3673palleviatesoxidativestressinjuryintheischemiareperfusioninjurycellmodelbytargetingnicotinamideadeninedinucleotidephosphateoxidase4mediatedkeap1nrf2arepathway
AT xingwentian mir3673palleviatesoxidativestressinjuryintheischemiareperfusioninjurycellmodelbytargetingnicotinamideadeninedinucleotidephosphateoxidase4mediatedkeap1nrf2arepathway
AT yujiezhang mir3673palleviatesoxidativestressinjuryintheischemiareperfusioninjurycellmodelbytargetingnicotinamideadeninedinucleotidephosphateoxidase4mediatedkeap1nrf2arepathway
AT qiongmu mir3673palleviatesoxidativestressinjuryintheischemiareperfusioninjurycellmodelbytargetingnicotinamideadeninedinucleotidephosphateoxidase4mediatedkeap1nrf2arepathway