Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784652109391593472 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8847737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhaoyinglong ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT zhongguohui ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT duruikai ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT zhaodingsheng ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT lijianwei ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT liyuheng ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT xingwenjuan ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT jinxiaoyan ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT zhangwenjuan ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT sunweijia ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT liucaizhi ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT liuzizhong ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT yuanxinxin ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT kanguanghan ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT hanxuan ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT liqi ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT changyanzhong ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT liyingxian ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy AT lingshukuan ckip13utrattenuatessimulatedmicrogravityinducedcardiacatrophy |