Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway

Although miR-327 had a protective effect on cardiomyocytes as described previously, the potential mechanism still needs further exploration. The aim of this study was to investigate the role and mechanism of miR-327 on oxidative stress in myocardial ischemia/reperfusion injury (MI/RI) process. Oxida...

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Main Authors: Tao Zheng, Jun Yang, Jing Zhang, Chaojun Yang, Zhixing Fan, Qi Li, Yuhong Zhai, Haiyin Liu, Jian Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.669146/full
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author Tao Zheng
Jun Yang
Jun Yang
Jing Zhang
Chaojun Yang
Zhixing Fan
Qi Li
Yuhong Zhai
Haiyin Liu
Jian Yang
author_facet Tao Zheng
Jun Yang
Jun Yang
Jing Zhang
Chaojun Yang
Zhixing Fan
Qi Li
Yuhong Zhai
Haiyin Liu
Jian Yang
author_sort Tao Zheng
collection DOAJ
description Although miR-327 had a protective effect on cardiomyocytes as described previously, the potential mechanism still needs further exploration. The aim of this study was to investigate the role and mechanism of miR-327 on oxidative stress in myocardial ischemia/reperfusion injury (MI/RI) process. Oxidative stress and cardiomyocytes injury were detected in rat model of MI/RI, hypoxia/reoxygenation (H/R), and tert-butyl hydroperoxide (TBHP) model of H9c2 cells. In vitro, downregulation of miR-327 inhibited both H/R- and TBHP-induced oxidative stress, and suppressed apoptosis. Meanwhile, fibroblast growth factor 10(FGF10) was enhanced by miR-327 knocked down, followed by the activation of p-PI3K and p-Akt, and the translocation of Nrf2. However, miR-327 overexpression performed with opposite effects. Consistent with the results in vitro, downregulation of miR-327 attenuated reactive oxygen species (ROS) generation as well as intrinsic apoptosis, and alleviated I/R injury. In conclusion, inhibition of miR-327 improved antioxidative ability and myocardial cell survival via regulating the FGF10/Akt/Nrf2 pathway.
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spelling doaj.art-7f8a7870a6684869a4b886f5b123d2d92022-12-21T21:33:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.669146669146Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling PathwayTao Zheng0Jun Yang1Jun Yang2Jing Zhang3Chaojun Yang4Zhixing Fan5Qi Li6Yuhong Zhai7Haiyin Liu8Jian Yang9Department of Cardiology, the First College of Clinical Medical Science, China Three Gorges University, Yichang, ChinaDepartment of Cardiology, the First College of Clinical Medical Science, China Three Gorges University, Yichang, ChinaHuBei Clinical Research Center for Ischemic Cardiovascular Disease, Yichang, ChinaDepartment of Cardiology, the First College of Clinical Medical Science, China Three Gorges University, Yichang, ChinaYichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, Yichang, ChinaYichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, Yichang, ChinaInstitute of Cardiovascular Disease, China Three Gorges University, Yichang, ChinaDepartment of Cardiology, the First College of Clinical Medical Science, China Three Gorges University, Yichang, ChinaDepartment of Cardiology, the First College of Clinical Medical Science, China Three Gorges University, Yichang, ChinaDepartment of Cardiology, the People’s Hospital of Three Gorges University, Yichang, ChinaAlthough miR-327 had a protective effect on cardiomyocytes as described previously, the potential mechanism still needs further exploration. The aim of this study was to investigate the role and mechanism of miR-327 on oxidative stress in myocardial ischemia/reperfusion injury (MI/RI) process. Oxidative stress and cardiomyocytes injury were detected in rat model of MI/RI, hypoxia/reoxygenation (H/R), and tert-butyl hydroperoxide (TBHP) model of H9c2 cells. In vitro, downregulation of miR-327 inhibited both H/R- and TBHP-induced oxidative stress, and suppressed apoptosis. Meanwhile, fibroblast growth factor 10(FGF10) was enhanced by miR-327 knocked down, followed by the activation of p-PI3K and p-Akt, and the translocation of Nrf2. However, miR-327 overexpression performed with opposite effects. Consistent with the results in vitro, downregulation of miR-327 attenuated reactive oxygen species (ROS) generation as well as intrinsic apoptosis, and alleviated I/R injury. In conclusion, inhibition of miR-327 improved antioxidative ability and myocardial cell survival via regulating the FGF10/Akt/Nrf2 pathway.https://www.frontiersin.org/articles/10.3389/fphar.2021.669146/fullmyocardial ischemia/reperfusion injuryoxidative stressmicroRNA-327FGF10apoptosis
spellingShingle Tao Zheng
Jun Yang
Jun Yang
Jing Zhang
Chaojun Yang
Zhixing Fan
Qi Li
Yuhong Zhai
Haiyin Liu
Jian Yang
Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway
Frontiers in Pharmacology
myocardial ischemia/reperfusion injury
oxidative stress
microRNA-327
FGF10
apoptosis
title Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway
title_full Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway
title_fullStr Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway
title_full_unstemmed Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway
title_short Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway
title_sort downregulated microrna 327 attenuates oxidative stress mediated myocardial ischemia reperfusion injury through regulating the fgf10 akt nrf2 signaling pathway
topic myocardial ischemia/reperfusion injury
oxidative stress
microRNA-327
FGF10
apoptosis
url https://www.frontiersin.org/articles/10.3389/fphar.2021.669146/full
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AT jianyang downregulatedmicrorna327attenuatesoxidativestressmediatedmyocardialischemiareperfusioninjurythroughregulatingthefgf10aktnrf2signalingpathway