TY - JOUR
T1 - Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel
AU - Suzuki, Norio
AU - Iwamura, Yuma
AU - Nakai, Taku
AU - Kato, Koichiro
AU - Otsuki, Akihito
AU - Uruno, Akira
AU - Saigusa, Daisuke
AU - Taguchi, Keiko
AU - Suzuki, Mikiko
AU - Shimizu, Ritsuko
AU - Yumoto, Akane
AU - Okada, Risa
AU - Shirakawa, Masaki
AU - Shiba, Dai
AU - Takahashi, Satoru
AU - Suzuki, Takafumi
AU - Yamamoto, Masayuki
N1 - Funding Information:
This study was supported by a space rodent research of the Japan Aerospace Exploration Agency’s (JAXA’s) feasibility study experiments using International Space Station (ISS)/Kibo, and supported in part by MEXT / JSPS KAKENHI ( 21H02676 to NS; 20K07352 to AU; 19H05649 to MY), and the Takeda Science Foundation (to NS). The funders have no role in this study. We thank Atsuko Konuma, Eriko Naganuma, Hiromi Suda (Tohoku University), and Keizo Nishikawa (Doshisha University) for technical help. We thank Hiroyasu Mizuno (JAXA) and Hiromi Suzuki-Hashizume (the Japan Space Forum) for implementation of the space experiment. We also thank the Biomedical Research Core and Centre for Laboratory Animal Research of Tohoku University for technical support.
Funding Information:
This study was supported by a space rodent research of the Japan Aerospace Exploration Agency's (JAXA's) feasibility study experiments using International Space Station (ISS)/Kibo, and supported in part by MEXT/JSPS KAKENHI (21H02676 to NS; 20K07352 to AU; 19H05649 to MY), and the Takeda Science Foundation (to NS). The funders have no role in this study. We thank Atsuko Konuma, Eriko Naganuma, Hiromi Suda (Tohoku University), and Keizo Nishikawa (Doshisha University) for technical help. We thank Hiroyasu Mizuno (JAXA) and Hiromi Suzuki-Hashizume (the Japan Space Forum) for implementation of the space experiment. We also thank the Biomedical Research Core and Centre for Laboratory Animal Research of Tohoku University for technical support. NS, DSh, ST, TS, and MY developed the project and designed the study. NS, YI, TN, KK, AO, AU, DSa, KT, MSu, RS, AY, RO, MSh, and TS performed the experiments and analyzed the data. NS and MY constructed the figures and wrote the manuscript. All of the authors discussed the results and suggested revisions.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - bioactive lipids
KW - genetically modified mouse
KW - stress response
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U2 - 10.1016/j.kint.2021.09.031
DO - 10.1016/j.kint.2021.09.031
M3 - Article
AN - SCOPUS:85120617433
VL - 101
SP - 92
EP - 105
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 1
ER -