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Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy
High morbidity and mortality are the most typical characteristics of septic cardiomyopathy. We aimed to reveal the role of miR-22 in septic cardiomyopathy and to explore the underlying mechanisms. miR-22 cardiac-specific knockout (miR-22(cKO)) mice and miR-22 cardiac-specific transgenic (miR-22(cOE)...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047209/ https://www.ncbi.nlm.nih.gov/pubmed/33869205 http://dx.doi.org/10.3389/fcell.2021.650666 |
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author | Wang, Runze Xu, Yuerong Zhang, Wei Fang, Yexian Yang, Tiqun Zeng, Di Wei, Ting Liu, Jing Zhou, Haijia Li, Yan Huang, Zhan-peng Zhang, Mingming |
author_facet | Wang, Runze Xu, Yuerong Zhang, Wei Fang, Yexian Yang, Tiqun Zeng, Di Wei, Ting Liu, Jing Zhou, Haijia Li, Yan Huang, Zhan-peng Zhang, Mingming |
author_sort | Wang, Runze |
collection | PubMed |
description | High morbidity and mortality are the most typical characteristics of septic cardiomyopathy. We aimed to reveal the role of miR-22 in septic cardiomyopathy and to explore the underlying mechanisms. miR-22 cardiac-specific knockout (miR-22(cKO)) mice and miR-22 cardiac-specific transgenic (miR-22(cOE)) mice were subjected to a cecal ligation and puncture (CLP) operation, while a sham operation was used in the control group. The echocardiogram results suggested that miR-22(cKO) CLP mice cardiac dysfunction was alleviated. The serum LDH and CK-MB were reduced in the miR-22(cKO) CLP mice. As expected, there was reduced apoptosis, increased autophagy and alleviated mitochondrial dysfunction in the miR-22(cKO) CLP mice, while it had contrary role in the miR-22(cOE) group. Inhibiting miR-22 promoted autophagy by increasing the LC3II/GAPDH ratio and decreasing the p62 level. Additionally, culturing primary cardiomyocytes with lipopolysaccharide (LPS) simulated sepsis-induced cardiomyopathy in vitro. Inhibiting miR-22 promoted autophagic flux confirmed by an increased LC3II/GAPDH ratio and reduced p62 protein level under bafilomycin A1 conditions. Knocking out miR-22 may exert a cardioprotective effect on sepsis by increasing autophagy and decreasing apoptosis via sirt1. Our results revealed that targeting miR-22 may become a new strategy for septic cardiomyopathy treatment. |
format | Online Article Text |
id | pubmed-8047209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80472092021-04-16 Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy Wang, Runze Xu, Yuerong Zhang, Wei Fang, Yexian Yang, Tiqun Zeng, Di Wei, Ting Liu, Jing Zhou, Haijia Li, Yan Huang, Zhan-peng Zhang, Mingming Front Cell Dev Biol Cell and Developmental Biology High morbidity and mortality are the most typical characteristics of septic cardiomyopathy. We aimed to reveal the role of miR-22 in septic cardiomyopathy and to explore the underlying mechanisms. miR-22 cardiac-specific knockout (miR-22(cKO)) mice and miR-22 cardiac-specific transgenic (miR-22(cOE)) mice were subjected to a cecal ligation and puncture (CLP) operation, while a sham operation was used in the control group. The echocardiogram results suggested that miR-22(cKO) CLP mice cardiac dysfunction was alleviated. The serum LDH and CK-MB were reduced in the miR-22(cKO) CLP mice. As expected, there was reduced apoptosis, increased autophagy and alleviated mitochondrial dysfunction in the miR-22(cKO) CLP mice, while it had contrary role in the miR-22(cOE) group. Inhibiting miR-22 promoted autophagy by increasing the LC3II/GAPDH ratio and decreasing the p62 level. Additionally, culturing primary cardiomyocytes with lipopolysaccharide (LPS) simulated sepsis-induced cardiomyopathy in vitro. Inhibiting miR-22 promoted autophagic flux confirmed by an increased LC3II/GAPDH ratio and reduced p62 protein level under bafilomycin A1 conditions. Knocking out miR-22 may exert a cardioprotective effect on sepsis by increasing autophagy and decreasing apoptosis via sirt1. Our results revealed that targeting miR-22 may become a new strategy for septic cardiomyopathy treatment. Frontiers Media S.A. 2021-04-01 /pmc/articles/PMC8047209/ /pubmed/33869205 http://dx.doi.org/10.3389/fcell.2021.650666 Text en Copyright © 2021 Wang, Xu, Zhang, Fang, Yang, Zeng, Wei, Liu, Zhou, Li, Huang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Wang, Runze Xu, Yuerong Zhang, Wei Fang, Yexian Yang, Tiqun Zeng, Di Wei, Ting Liu, Jing Zhou, Haijia Li, Yan Huang, Zhan-peng Zhang, Mingming Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy |
title | Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy |
title_full | Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy |
title_fullStr | Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy |
title_full_unstemmed | Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy |
title_short | Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy |
title_sort | inhibiting mir-22 alleviates cardiac dysfunction by regulating sirt1 in septic cardiomyopathy |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047209/ https://www.ncbi.nlm.nih.gov/pubmed/33869205 http://dx.doi.org/10.3389/fcell.2021.650666 |
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