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 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.796902

DOI=10.3389/fcell.2021.796902

ISSN=2296-634X

ABSTRACT=Microgravity prominently affected cardiovascular health which was the gravity-dependence 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 in the cardiac atrophy exposed to microgravity currently remained limited. 3' untranslated region 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 monkeys 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 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 acids oxidation-related genes expression in the hearts through targeting CaMKK2 and activation AMPK-PPARα-CPT1b signaling pathway. These findings demonstrated Ckip-1 3' UTR was an important regulator in atrophic heart growth after simulated microgravity.