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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Frontiers Media S.A.
2021-05-01
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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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