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miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway

BACKGROUND: MicroRNA (miRNA), which participates in various physiological and pathological processes, is a highly conserved small RNA sequence. This study aimed to investigate the role of miR-194-5p in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis and myocardial ischemia/reperfusion (I...

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Autores principales: Zhang, Qiufeng, Wu, Xiaotian, Yang, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106072/
https://www.ncbi.nlm.nih.gov/pubmed/33987352
http://dx.doi.org/10.21037/atm-21-807
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author Zhang, Qiufeng
Wu, Xiaotian
Yang, Jie
author_facet Zhang, Qiufeng
Wu, Xiaotian
Yang, Jie
author_sort Zhang, Qiufeng
collection PubMed
description BACKGROUND: MicroRNA (miRNA), which participates in various physiological and pathological processes, is a highly conserved small RNA sequence. This study aimed to investigate the role of miR-194-5p in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis and myocardial ischemia/reperfusion (I/R) injury. METHODS: We set up an H/R H9c2 cell model in vitro and an I/R mouse model in vivo. Then, cell vitality, apoptosis, and histopathological evaluation were conducted. Reactive oxygen species (ROS) generation and the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined by 2’,7’-Dichlorodihydrofluorescein diacetate (H2DCFDA), and enzyme-linked immunosorbent assay (ELISA), respectively. The level of creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), myoglobin (Mb) is examined by ELISA. The expression of Caspase-3, cleaved-Caspase-3, Bax, Bcl-2, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and protein kinase B (AKT) was analyzed by western blot. RESULTS: Data showed the expression of miR-194-5p was decreased in H/R-induced H9c2 cells and I/R-induced mouse. Conversely, overexpression of miR-194-5p could improve cardiomyocyte damage in ischemic models in vivo and in vitro. Furthermore, mitogen-activated protein kinase 1 (MAPK1) was found as a direct target of miR-194-5p, which negatively regulated the expression of MAPK1. The up-regulation of MAPK1 inhibited the myocardial protection previously observed by miR-194-5p. CONCLUSIONS: Our study shows overexpression of miR-194-5p protects against H/R injury in vitro and cardiac I/R injury in vivo, which involves the inhibition of cardiac apoptosis and oxidative stress by targeting MAPK1 expression via PTEN/AKT pathway. These findings supply novel insights into potential therapeutic targets for cardiovascular diseases.
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spelling pubmed-81060722021-05-12 miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway Zhang, Qiufeng Wu, Xiaotian Yang, Jie Ann Transl Med Original Article BACKGROUND: MicroRNA (miRNA), which participates in various physiological and pathological processes, is a highly conserved small RNA sequence. This study aimed to investigate the role of miR-194-5p in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis and myocardial ischemia/reperfusion (I/R) injury. METHODS: We set up an H/R H9c2 cell model in vitro and an I/R mouse model in vivo. Then, cell vitality, apoptosis, and histopathological evaluation were conducted. Reactive oxygen species (ROS) generation and the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined by 2’,7’-Dichlorodihydrofluorescein diacetate (H2DCFDA), and enzyme-linked immunosorbent assay (ELISA), respectively. The level of creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), myoglobin (Mb) is examined by ELISA. The expression of Caspase-3, cleaved-Caspase-3, Bax, Bcl-2, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and protein kinase B (AKT) was analyzed by western blot. RESULTS: Data showed the expression of miR-194-5p was decreased in H/R-induced H9c2 cells and I/R-induced mouse. Conversely, overexpression of miR-194-5p could improve cardiomyocyte damage in ischemic models in vivo and in vitro. Furthermore, mitogen-activated protein kinase 1 (MAPK1) was found as a direct target of miR-194-5p, which negatively regulated the expression of MAPK1. The up-regulation of MAPK1 inhibited the myocardial protection previously observed by miR-194-5p. CONCLUSIONS: Our study shows overexpression of miR-194-5p protects against H/R injury in vitro and cardiac I/R injury in vivo, which involves the inhibition of cardiac apoptosis and oxidative stress by targeting MAPK1 expression via PTEN/AKT pathway. These findings supply novel insights into potential therapeutic targets for cardiovascular diseases. AME Publishing Company 2021-04 /pmc/articles/PMC8106072/ /pubmed/33987352 http://dx.doi.org/10.21037/atm-21-807 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Zhang, Qiufeng
Wu, Xiaotian
Yang, Jie
miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway
title miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway
title_full miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway
title_fullStr miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway
title_full_unstemmed miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway
title_short miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway
title_sort mir-194-5p protects against myocardial ischemia/reperfusion injury via mapk1/pten/akt pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106072/
https://www.ncbi.nlm.nih.gov/pubmed/33987352
http://dx.doi.org/10.21037/atm-21-807
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