Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel
Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel
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太空旅行后小鼠肾脏中与骨矿化、血压和脂质代谢相关的基因表达变化
DOI：
10.1016/j.kint.2021.09.031
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发表时间：
2022
影响因子：
19.6
通讯作者：
Yamamoto Masayuki
中科院分区：
文献类型：
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作者：
Suzuki Norio;Iwamura Yuma;Nakai Taku;Kato Koichiro;Otsuki Akihito;Uruno Akira;Saigusa Daisuke;Taguchi Keiko;Suzuki Mikiko;Shimizu Ritsuko;Yumoto Akane;Okada Risa;Shirakawa Masaki;Shiba Dai;Takahashi Satoru;Suzuki Takafumi;Yamamoto Masayuki
太空旅行由于放射性和微重力而造成相当大的环境压力，给健康带来负担。特别是，重力变化主要影响血压和骨稳态，这两者主要由肾脏控制。核因子红细胞-2相关转录因子2（Nrf 2）在保护肾脏免受各种环境应激和损伤中起重要作用。为了阐明太空旅行对哺乳动物的影响，为即将到来的太空时代做准备，我们的研究调查了Nrf 2基因敲除小鼠在国际空间站停留31天后返回两天后Nrf 2对小鼠肾功能的贡献。有意义的是，研究发现，在太空旅行后，肾脏中调节骨矿化、血压和脂质代谢的基因表达水平以Nrf 2非依赖性方式发生了显著变化。特别是，尿苷二磷酸-葡萄糖醛酸转移酶1A（Ugt 1a）亚型基因被发现以Nrf 2依赖的方式表达，并在返回地球后仅在肾脏中诱导。由于太空飞行提高了小鼠血浆中脂肪酸的浓度，我们认为肾脏中的Ugt 1a亚型表达被诱导，以促进过度积累的脂质的葡萄糖醛酸化，并在从太空返回后将其排泄到尿液中。因此，肾脏被证明通过控制血压和骨矿化，在适应太空往返引起的重力变化方面发挥着核心作用。此外，太空旅行后肾脏Ugt 1a亚型的诱导意味着太空旅行者的肾脏在过量脂质的排泄中起着重要作用。
Space travel burdens health by imposing considerable environmental stress associated with radioactivity and microgravity. In particular, gravity change predominantly impacts blood pressure and bone homeostasis, both of which are controlled mainly by the kidneys. Nuclear factor erythroid-2-related transcription factor 2 (Nrf2) plays essential roles in protecting the kidneys from various environmental stresses and injuries. To elucidate the effects of space travel on mammals in preparation for the upcoming space era, our study investigated the contribution of Nrf2 to kidney function in mice two days after their return from a 31-day stay in the International Space Station using Nrf2 knockout mice. Meaningfully, expression levels of genes regulating bone mineralization, blood pressure and lipid metabolism were found to be significantly altered in the kidneys after space travel in an Nrf2-independent manner. In particular, uridine diphosphate-glucuronosyltransferase 1A (Ugt1a) isoform genes were found to be expressed in an Nrf2-dependent manner and induced exclusively in the kidneys after return to Earth. Since spaceflight elevated the concentrations of fatty acids in the mouse plasma, we suggest that Ugt1a isoform expression in the kidneys was induced to promote glucuronidation of excessively accumulated lipids and excrete them into urine after the return from space. Thus, the kidneys were proven to play central roles in adaptation to gravity changes caused by going to and returning from space by controlling blood pressure and bone mineralization. Additionally, kidney Ugt1a isoform induction after space travel implies a significant role of the kidneys for space travelers in the excretion of excessive lipids.