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Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy

Microgravity prominently affected cardiovascular health, which was the gravity-dependent physical factor. Deep space exploration had been increasing in frequency, but heart function was susceptible to conspicuous damage and cardiac mass declined in weightlessness. Understanding of the etiology of ca...

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Autores principales: Zhao, Yinglong, Zhong, Guohui, Du, Ruikai, Zhao, Dingsheng, Li, Jianwei, Li, Yuheng, Xing, Wenjuan, Jin, Xiaoyan, Zhang, Wenjuan, Sun, Weijia, Liu, Caizhi, Liu, Zizhong, Yuan, Xinxin, Kan, Guanghan, Han, Xuan, Li, Qi, Chang, Yan-Zhong, Li, Yingxian, Ling, Shukuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847737/
https://www.ncbi.nlm.nih.gov/pubmed/35186951
http://dx.doi.org/10.3389/fcell.2021.796902
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author Zhao, Yinglong
Zhong, Guohui
Du, Ruikai
Zhao, Dingsheng
Li, Jianwei
Li, Yuheng
Xing, Wenjuan
Jin, Xiaoyan
Zhang, Wenjuan
Sun, Weijia
Liu, Caizhi
Liu, Zizhong
Yuan, Xinxin
Kan, Guanghan
Han, Xuan
Li, Qi
Chang, Yan-Zhong
Li, Yingxian
Ling, Shukuan
author_facet Zhao, Yinglong
Zhong, Guohui
Du, Ruikai
Zhao, Dingsheng
Li, Jianwei
Li, Yuheng
Xing, Wenjuan
Jin, Xiaoyan
Zhang, Wenjuan
Sun, Weijia
Liu, Caizhi
Liu, Zizhong
Yuan, Xinxin
Kan, Guanghan
Han, Xuan
Li, Qi
Chang, Yan-Zhong
Li, Yingxian
Ling, Shukuan
author_sort Zhao, Yinglong
collection PubMed
description Microgravity prominently affected cardiovascular health, which was the gravity-dependent physical factor. Deep space exploration had been increasing in frequency, but heart function was susceptible to conspicuous damage and cardiac mass declined in weightlessness. Understanding of the etiology of cardiac atrophy exposed to microgravity currently remains limited. The 3′-untranslated region (UTR) of casein kinase-2 interacting protein-1 (Ckip-1) was a pivotal mediator in pressure overload-induced cardiac remodeling. However, the role of Ckip-1 3′-UTR in the heart during microgravity was unknown. We analyzed Ckip-1 mRNA 3′-UTR and coding sequence (CDS) expression levels in ground-based analogs such as mice hindlimb unloading (HU) and rhesus monkey head-down bed rest model. Ckip-1 3′-UTR had transcribed levels in the opposite change trend with cognate CDS expression in the hearts. We then subjected wild-type (WT) mice and cardiac-specific Ckip-1 3′-UTR-overexpressing mice to hindlimb unloading for 28 days. Our results uncovered that Ckip-1 3′-UTR remarkably attenuated cardiac dysfunction and mass loss in simulated microgravity environments. Mechanistically, Ckip-1 3′-UTR inhibited lipid accumulation and elevated fatty acid oxidation-related gene expression in the hearts through targeting calcium/calmodulin-dependent kinase 2 (CaMKK2) and activation of the AMPK-PPARα-CPT1b signaling pathway. These findings demonstrated Ckip-1 3′-UTR was an important regulator in atrophic heart growth after simulated microgravity.
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spelling pubmed-88477372022-02-17 Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy Zhao, Yinglong Zhong, Guohui Du, Ruikai Zhao, Dingsheng Li, Jianwei Li, Yuheng Xing, Wenjuan Jin, Xiaoyan Zhang, Wenjuan Sun, Weijia Liu, Caizhi Liu, Zizhong Yuan, Xinxin Kan, Guanghan Han, Xuan Li, Qi Chang, Yan-Zhong Li, Yingxian Ling, Shukuan Front Cell Dev Biol Cell and Developmental Biology Microgravity prominently affected cardiovascular health, which was the gravity-dependent physical factor. Deep space exploration had been increasing in frequency, but heart function was susceptible to conspicuous damage and cardiac mass declined in weightlessness. Understanding of the etiology of cardiac atrophy exposed to microgravity currently remains limited. The 3′-untranslated region (UTR) of casein kinase-2 interacting protein-1 (Ckip-1) was a pivotal mediator in pressure overload-induced cardiac remodeling. However, the role of Ckip-1 3′-UTR in the heart during microgravity was unknown. We analyzed Ckip-1 mRNA 3′-UTR and coding sequence (CDS) expression levels in ground-based analogs such as mice hindlimb unloading (HU) and rhesus monkey head-down bed rest model. Ckip-1 3′-UTR had transcribed levels in the opposite change trend with cognate CDS expression in the hearts. We then subjected wild-type (WT) mice and cardiac-specific Ckip-1 3′-UTR-overexpressing mice to hindlimb unloading for 28 days. Our results uncovered that Ckip-1 3′-UTR remarkably attenuated cardiac dysfunction and mass loss in simulated microgravity environments. Mechanistically, Ckip-1 3′-UTR inhibited lipid accumulation and elevated fatty acid oxidation-related gene expression in the hearts through targeting calcium/calmodulin-dependent kinase 2 (CaMKK2) and activation of the AMPK-PPARα-CPT1b signaling pathway. These findings demonstrated Ckip-1 3′-UTR was an important regulator in atrophic heart growth after simulated microgravity. Frontiers Media S.A. 2022-02-02 /pmc/articles/PMC8847737/ /pubmed/35186951 http://dx.doi.org/10.3389/fcell.2021.796902 Text en Copyright © 2022 Zhao, Zhong, Du, Zhao, Li, Li, Xing, Jin, Zhang, Sun, Liu, Liu, Yuan, Kan, Han, Li, Chang, Li and Ling. 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
Zhao, Yinglong
Zhong, Guohui
Du, Ruikai
Zhao, Dingsheng
Li, Jianwei
Li, Yuheng
Xing, Wenjuan
Jin, Xiaoyan
Zhang, Wenjuan
Sun, Weijia
Liu, Caizhi
Liu, Zizhong
Yuan, Xinxin
Kan, Guanghan
Han, Xuan
Li, Qi
Chang, Yan-Zhong
Li, Yingxian
Ling, Shukuan
Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy
title Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy
title_full Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy
title_fullStr Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy
title_full_unstemmed Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy
title_short Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy
title_sort ckip-1 3′-utr attenuates simulated microgravity-induced cardiac atrophy
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847737/
https://www.ncbi.nlm.nih.gov/pubmed/35186951
http://dx.doi.org/10.3389/fcell.2021.796902
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