MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusion

Abstract Acute myocardial infarction (AMI) remains one of the leading causes of morbidity and mortality worldwide. Ischemia/reperfusion (I/R), the most common consequence of AMI treatment, may induce severe myocardial cell injury, yet the precise mechanism continues to be enigmatic. In the present s...

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Main Authors: Rui Ma, Xin Chen, Yue Ma, Gang Bai, Dong‐Sheng Li
Format: Article
Language:English
Published: Wiley 2020-08-01
Series:Kaohsiung Journal of Medical Sciences
Subjects:
Online Access:https://doi.org/10.1002/kjm2.12211
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author Rui Ma
Xin Chen
Yue Ma
Gang Bai
Dong‐Sheng Li
author_facet Rui Ma
Xin Chen
Yue Ma
Gang Bai
Dong‐Sheng Li
author_sort Rui Ma
collection DOAJ
description Abstract Acute myocardial infarction (AMI) remains one of the leading causes of morbidity and mortality worldwide. Ischemia/reperfusion (I/R), the most common consequence of AMI treatment, may induce severe myocardial cell injury, yet the precise mechanism continues to be enigmatic. In the present study, we found that miR‐129‐5p was significantly downregulated in mouse I/R model. Then, we overexpressed miR‐129‐5p via intravenous injection of specific miR‐129‐5p agomir before I/R model establishment. MiR‐129‐5p overexpression dramatically alleviated myocardial injury in I/R mice as evidenced by reduced lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) content, and infract size. We further detected the effect of miR‐129‐5p on hypoxia/reoxygenation (H/R)‐induced H9C2 cell in vitro. MiR‐129‐5p overexpression improved H9C2 cell viability and inhibited cell apoptosis induced by H/R, accompanied with decreased LDH activity and MDA content. Besides, luciferase reporter assay indicated that suppressor of cytokine signaling 2 (SOCS2) was a downstream target of miR‐129‐5p. SOCS2 was upregulated in H/R induced H9C2 cells, and miR‐129‐5p overexpression suppressed SOCS2 expression at both mRNA and protein levels. In addition, SOCS2 overexpression abolished the protective effects of miR‐129‐5p on H/R‐induced H9C2 cells, concomitant with elevated expression of apoptosis‐related cleaved poly‐(ADP‐ribose) polymerase and cleaved caspase‐3. In conclusion, our results demonstrated that miR‐129‐5p alleviated myocardial injury induced by I/R both in vitro and in vivo, and miR‐129‐5p/SOCS2 axis is a potential therapeutic target for alleviating myocardial injury in AMI patients after reperfusion.
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spelling doaj.art-8561535ee1e5478da659473cdd2c42cd2023-12-13T07:10:58ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502020-08-0136859960610.1002/kjm2.12211MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusionRui Ma0Xin Chen1Yue Ma2Gang Bai3Dong‐Sheng Li4Department of Geriatrics National Pharmacy Dongfeng General Hospital Shiyan ChinaDepartment of Geriatrics National Pharmacy Dongfeng General Hospital Shiyan ChinaDepartment of Spine National Pharmacy Dongfeng General Hospital Shiyan ChinaDepartment of Ultrasonography Tai He Hospital Shiyan ChinaDepartment of Cardiology Wuhan Third Hospital‐Tongren Hospital of Wuhan University Wuhan ChinaAbstract Acute myocardial infarction (AMI) remains one of the leading causes of morbidity and mortality worldwide. Ischemia/reperfusion (I/R), the most common consequence of AMI treatment, may induce severe myocardial cell injury, yet the precise mechanism continues to be enigmatic. In the present study, we found that miR‐129‐5p was significantly downregulated in mouse I/R model. Then, we overexpressed miR‐129‐5p via intravenous injection of specific miR‐129‐5p agomir before I/R model establishment. MiR‐129‐5p overexpression dramatically alleviated myocardial injury in I/R mice as evidenced by reduced lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) content, and infract size. We further detected the effect of miR‐129‐5p on hypoxia/reoxygenation (H/R)‐induced H9C2 cell in vitro. MiR‐129‐5p overexpression improved H9C2 cell viability and inhibited cell apoptosis induced by H/R, accompanied with decreased LDH activity and MDA content. Besides, luciferase reporter assay indicated that suppressor of cytokine signaling 2 (SOCS2) was a downstream target of miR‐129‐5p. SOCS2 was upregulated in H/R induced H9C2 cells, and miR‐129‐5p overexpression suppressed SOCS2 expression at both mRNA and protein levels. In addition, SOCS2 overexpression abolished the protective effects of miR‐129‐5p on H/R‐induced H9C2 cells, concomitant with elevated expression of apoptosis‐related cleaved poly‐(ADP‐ribose) polymerase and cleaved caspase‐3. In conclusion, our results demonstrated that miR‐129‐5p alleviated myocardial injury induced by I/R both in vitro and in vivo, and miR‐129‐5p/SOCS2 axis is a potential therapeutic target for alleviating myocardial injury in AMI patients after reperfusion.https://doi.org/10.1002/kjm2.12211ischemia/reperfusionmiR‐129‐5pmyocardial injurySOCS2
spellingShingle Rui Ma
Xin Chen
Yue Ma
Gang Bai
Dong‐Sheng Li
MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusion
Kaohsiung Journal of Medical Sciences
ischemia/reperfusion
miR‐129‐5p
myocardial injury
SOCS2
title MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusion
title_full MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusion
title_fullStr MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusion
title_full_unstemmed MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusion
title_short MiR‐129‐5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia/reperfusion
title_sort mir 129 5p alleviates myocardial injury by targeting suppressor of cytokine signaling 2 after ischemia reperfusion
topic ischemia/reperfusion
miR‐129‐5p
myocardial injury
SOCS2
url https://doi.org/10.1002/kjm2.12211
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AT yuema mir1295palleviatesmyocardialinjurybytargetingsuppressorofcytokinesignaling2afterischemiareperfusion
AT gangbai mir1295palleviatesmyocardialinjurybytargetingsuppressorofcytokinesignaling2afterischemiareperfusion
AT dongshengli mir1295palleviatesmyocardialinjurybytargetingsuppressorofcytokinesignaling2afterischemiareperfusion