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WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity

Cardiac muscle is extremely sensitive to changes in loading conditions; the microgravity during space flight can cause cardiac remodeling and function decline. At present, the mechanism of microgravity-induced cardiac remodeling remains to be revealed. WW domain-containing E3 ubiquitin protein ligas...

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Autores principales: Zhong, Guohui, Zhao, Dingsheng, Li, Jianwei, Liu, Zifan, Pan, Junjie, Yuan, Xinxin, Xing, Wenjuan, Zhao, Yinglong, Ling, Shukuan, Li, Yingxian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558417/
https://www.ncbi.nlm.nih.gov/pubmed/34733849
http://dx.doi.org/10.3389/fcell.2021.739944
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author Zhong, Guohui
Zhao, Dingsheng
Li, Jianwei
Liu, Zifan
Pan, Junjie
Yuan, Xinxin
Xing, Wenjuan
Zhao, Yinglong
Ling, Shukuan
Li, Yingxian
author_facet Zhong, Guohui
Zhao, Dingsheng
Li, Jianwei
Liu, Zifan
Pan, Junjie
Yuan, Xinxin
Xing, Wenjuan
Zhao, Yinglong
Ling, Shukuan
Li, Yingxian
author_sort Zhong, Guohui
collection PubMed
description Cardiac muscle is extremely sensitive to changes in loading conditions; the microgravity during space flight can cause cardiac remodeling and function decline. At present, the mechanism of microgravity-induced cardiac remodeling remains to be revealed. WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is an important activator of pressure overload-induced cardiac remodeling by stabilizing disheveled segment polarity proteins 2 (DVL2) and activating the calcium-calmodulin-dependent protein kinase II (CaMKII)/histone deacetylase 4 (HDAC4)/myocyte-specific enhancer factor 2C (MEF2C) axis. However, the role of WWP1 in cardiac remodeling induced by microgravity is unknown. The purpose of this study was to determine whether WWP1 was also involved in the regulation of cardiac remodeling caused by microgravity. Firstly, we detected the expression of WWP1 and DVL2 in the heart from mice and monkeys after simulated microgravity using western blotting and immunohistochemistry. Secondly, WWP1 knockout (KO) and wild-type (WT) mice were subjected to tail suspension (TS) to simulate microgravity effect. We assessed the cardiac remodeling in morphology and function through a histological analysis and echocardiography. Finally, we detected the phosphorylation levels of CaMKII and HDAC4 in the hearts from WT and WWP1 KO mice after TS. The results revealed the increased expression of WWP1 and DVL2 in the hearts both from mice and monkeys after simulated microgravity. WWP1 deficiency alleviated simulated microgravity-induced cardiac atrophy and function decline. The histological analysis demonstrated WWP1 KO inhibited the decreases in the size of individual cardiomyocytes of mice after tail suspension. WWP1 KO can inhibit the activation of the DVL2/CaMKII/HDAC4 pathway in the hearts of mice induced by simulated microgravity. These results demonstrated WWP1 as a potential therapeutic target for cardiac remodeling and function decline induced by simulated microgravity.
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spelling pubmed-85584172021-11-02 WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity Zhong, Guohui Zhao, Dingsheng Li, Jianwei Liu, Zifan Pan, Junjie Yuan, Xinxin Xing, Wenjuan Zhao, Yinglong Ling, Shukuan Li, Yingxian Front Cell Dev Biol Cell and Developmental Biology Cardiac muscle is extremely sensitive to changes in loading conditions; the microgravity during space flight can cause cardiac remodeling and function decline. At present, the mechanism of microgravity-induced cardiac remodeling remains to be revealed. WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is an important activator of pressure overload-induced cardiac remodeling by stabilizing disheveled segment polarity proteins 2 (DVL2) and activating the calcium-calmodulin-dependent protein kinase II (CaMKII)/histone deacetylase 4 (HDAC4)/myocyte-specific enhancer factor 2C (MEF2C) axis. However, the role of WWP1 in cardiac remodeling induced by microgravity is unknown. The purpose of this study was to determine whether WWP1 was also involved in the regulation of cardiac remodeling caused by microgravity. Firstly, we detected the expression of WWP1 and DVL2 in the heart from mice and monkeys after simulated microgravity using western blotting and immunohistochemistry. Secondly, WWP1 knockout (KO) and wild-type (WT) mice were subjected to tail suspension (TS) to simulate microgravity effect. We assessed the cardiac remodeling in morphology and function through a histological analysis and echocardiography. Finally, we detected the phosphorylation levels of CaMKII and HDAC4 in the hearts from WT and WWP1 KO mice after TS. The results revealed the increased expression of WWP1 and DVL2 in the hearts both from mice and monkeys after simulated microgravity. WWP1 deficiency alleviated simulated microgravity-induced cardiac atrophy and function decline. The histological analysis demonstrated WWP1 KO inhibited the decreases in the size of individual cardiomyocytes of mice after tail suspension. WWP1 KO can inhibit the activation of the DVL2/CaMKII/HDAC4 pathway in the hearts of mice induced by simulated microgravity. These results demonstrated WWP1 as a potential therapeutic target for cardiac remodeling and function decline induced by simulated microgravity. Frontiers Media S.A. 2021-10-18 /pmc/articles/PMC8558417/ /pubmed/34733849 http://dx.doi.org/10.3389/fcell.2021.739944 Text en Copyright © 2021 Zhong, Zhao, Li, Liu, Pan, Yuan, Xing, Zhao, Ling and Li. 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
Zhong, Guohui
Zhao, Dingsheng
Li, Jianwei
Liu, Zifan
Pan, Junjie
Yuan, Xinxin
Xing, Wenjuan
Zhao, Yinglong
Ling, Shukuan
Li, Yingxian
WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity
title WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity
title_full WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity
title_fullStr WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity
title_full_unstemmed WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity
title_short WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity
title_sort wwp1 deficiency alleviates cardiac remodeling induced by simulated microgravity
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558417/
https://www.ncbi.nlm.nih.gov/pubmed/34733849
http://dx.doi.org/10.3389/fcell.2021.739944
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