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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.796902/full |
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| author | Yinglong Zhao Yinglong Zhao Guohui Zhong Guohui Zhong Ruikai Du Dingsheng Zhao Jianwei Li Yuheng Li Yuheng Li Wenjuan Xing Wenjuan Xing Xiaoyan Jin Wenjuan Zhang Weijia Sun Caizhi Liu Zizhong Liu Xinxin Yuan Guanghan Kan Xuan Han Qi Li Yan-Zhong Chang Yingxian Li Shukuan Ling |
| author_facet | Yinglong Zhao Yinglong Zhao Guohui Zhong Guohui Zhong Ruikai Du Dingsheng Zhao Jianwei Li Yuheng Li Yuheng Li Wenjuan Xing Wenjuan Xing Xiaoyan Jin Wenjuan Zhang Weijia Sun Caizhi Liu Zizhong Liu Xinxin Yuan Guanghan Kan Xuan Han Qi Li Yan-Zhong Chang Yingxian Li Shukuan Ling |
| author_sort | Yinglong Zhao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-24T03:26:16Z |
| format | Article |
| id | doaj.art-8259364f6af24044be184f31aabed650 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-24T03:26:16Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-8259364f6af24044be184f31aabed6502022-12-21T17:17:19ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-02-01910.3389/fcell.2021.796902796902Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac AtrophyYinglong Zhao0Yinglong Zhao1Guohui Zhong2Guohui Zhong3Ruikai Du4Dingsheng Zhao5Jianwei Li6Yuheng Li7Yuheng Li8Wenjuan Xing9Wenjuan Xing10Xiaoyan Jin11Wenjuan Zhang12Weijia Sun13Caizhi Liu14Zizhong Liu15Xinxin Yuan16Guanghan Kan17Xuan Han18Qi Li19Yan-Zhong Chang20Yingxian Li21Shukuan Ling22State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaKey Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaSchool of Aerospace Medicine, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaSchool of Aerospace Medicine, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaSchool of Aerospace Medicine, Fourth Military Medical University, Xi’an, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Proteomics, National Center of Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaKey Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaState Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, ChinaMicrogravity 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.796902/fullCkip-1 3′-UTRsimulated microgravitycardiac atrophylipid accumulationCaMKK2 |
| spellingShingle | Yinglong Zhao Yinglong Zhao Guohui Zhong Guohui Zhong Ruikai Du Dingsheng Zhao Jianwei Li Yuheng Li Yuheng Li Wenjuan Xing Wenjuan Xing Xiaoyan Jin Wenjuan Zhang Weijia Sun Caizhi Liu Zizhong Liu Xinxin Yuan Guanghan Kan Xuan Han Qi Li Yan-Zhong Chang Yingxian Li Shukuan Ling Ckip-1 3′-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy Frontiers in Cell and Developmental Biology Ckip-1 3′-UTR simulated microgravity cardiac atrophy lipid accumulation CaMKK2 |
| 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 | Ckip-1 3′-UTR simulated microgravity cardiac atrophy lipid accumulation CaMKK2 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.796902/full |
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