Abstract
Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.
| Original language | English |
|---|---|
| Article number | 4923 |
| Number of pages | 20 |
| Journal | Nature Communications |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 2024 |
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In: Nature Communications, Vol. 15, No. 1, 4923, 12.2024.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Cosmic kidney disease
T2 - an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction
AU - Siew, Keith
AU - Nestler, Kevin A.
AU - Nelson, Charlotte
AU - D’Ambrosio, Viola
AU - Zhong, Chutong
AU - Li, Zhongwang
AU - Grillo, Alessandra
AU - Wan, Elizabeth R.
AU - Patel, Vaksha
AU - Overbey, Eliah
AU - Kim, Jang Keun
AU - Yun, Sanghee
AU - Vaughan, Michael B.
AU - Cheshire, Chris
AU - Cubitt, Laura
AU - Broni-Tabi, Jessica
AU - Al-Jaber, Maneera Yousef
AU - Boyko, Valery
AU - Meydan, Cem
AU - Barker, Peter
AU - Arif, Shehbeel
AU - Afsari, Fatemeh
AU - Allen, Noah
AU - Al-Maadheed, Mohammed
AU - Altinok, Selin
AU - Bah, Nourdine
AU - Border, Samuel
AU - Brown, Amanda L.
AU - Burling, Keith
AU - Cheng-Campbell, Margareth
AU - Colón, Lorianna M.
AU - Degoricija, Lovorka
AU - Figg, Nichola
AU - Finch, Rebecca
AU - Foox, Jonathan
AU - Faridi, Pouya
AU - French, Alison
AU - Gebre, Samrawit
AU - Gordon, Peter
AU - Houerbi, Nadia
AU - Valipour Kahrood, Hossein
AU - Kiffer, Frederico C.
AU - Klosinska, Aleksandra S.
AU - Kubik, Angela
AU - Lee, Han Chung
AU - Li, Yinghui
AU - Lucarelli, Nicholas
AU - Marullo, Anthony L.
AU - Matei, Irina
AU - McCann, Colleen M.
AU - Mimar, Sayat
AU - Naglah, Ahmed
AU - Nicod, Jérôme
AU - O’Shaughnessy, Kevin M.
AU - Oliveira, Lorraine Christine De
AU - Oswalt, Leah
AU - Patras, Laura Ioana
AU - Lai Polo, San Huei
AU - Rodríguez-Lopez, María
AU - Roufosse, Candice
AU - Sadeghi-Alavijeh, Omid
AU - Sanchez-Hodge, Rebekah
AU - Paul, Anindya S.
AU - Schittenhelm, Ralf Bernd
AU - Schweickart, Annalise
AU - Scott, Ryan T.
AU - Choy Lim Kam Sian, Terry Chin
AU - da Silveira, Willian A.
AU - Slawinski, Hubert
AU - Snell, Daniel
AU - Sosa, Julio
AU - Saravia-Butler, Amanda M.
AU - Tabetah, Marshall
AU - Tanuwidjaya, Erwin
AU - Walker-Samuel, Simon
AU - Yang, Xiaoping
AU - Yasmin, null
AU - Zhang, Haijian
AU - Godovac-Zimmermann, Jasminka
AU - Sarder, Pinaki
AU - Sanders, Lauren M.
AU - Costes, Sylvain V.
AU - Campbell, Robert A.A.
AU - Karouia, Fathi
AU - Mohamed-Alis, Vidya
AU - Rodriques, Samuel
AU - Lynham, Steven
AU - Steele, Joel Ricky
AU - Baranzini, Sergio
AU - Fazelinia, Hossein
AU - Dai, Zhongquan
AU - Uruno, Akira
AU - Shiba, Dai
AU - Yamamoto, Masayuki
AU - A.C.Almeida, Eduardo
AU - Blaber, Elizabeth
AU - Schisler, Jonathan C.
AU - Eisch, Amelia J.
AU - Muratani, Masafumi
AU - Zwart, Sara R.
AU - Smith, Scott M.
AU - Galazka, Jonathan M.
AU - Mason, Christopher E.
AU - Beheshti, Afshin
AU - Walsh, Stephen B.
N1 - Funding Information: S.B.W. and K.S. acknowledges this work was partially funded by the UK Space Agency through a grant [ST/X000036/1] administered by the Science and Technology Facilities Council (STFC). S.B.W. is supported by Kidney Research UK grant [RP_017_20190306] and St Peters Trust. K.S. acknowledges this research was funded in part by the Wellcome Trust [Grant number 110282/Z/15/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. A.G. is supported by Kidney Research UK (RP_017_20190306). E.R.W. is supported by Kidney Research UK, TF_007_20191202. J.K. thanks MOGAM Science Foundation. J.K. was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (RS-2023-00241586). S.Y. received 2021 NASA HERO grant 80NSSC21K0814 and Augmentation award, 2019 NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation, 2020 PENN Undergraduate Research Foundation grant; MH076690, and by NIH DK135871 (PI Zderic), R01 NS088555 (PI: AM Stowe), R15 MH117628 (PI: K. Lambert). M.B.V. received Eli Lilly Doctoral Scholarship. L.C. received funding support from the Francis Crick Institute (CC2168). J.B.T., P.G. and R.A.A.C. are supported by the Sainsbury Wellcome Centre\u2019s core provided by Wellcome (219627/Z/19/Z) and the Gatsby Charitable Foundation (GAT3755). L.M.C. received Penn Provost/CHOP Postdoctoral Fellowship for Academic Diversity, Burroughs Wellcome Fund Postdoctoral Diversity Enrichment Program. S.G. and S.L.P. are supported by the GeneLab Project at NASA Ames Research Center, through NASA\u2019s Biological and Physical Sciences (BPS) Division in the Science Mission Directorate (SMD). F.C.K. is supported by Translational Research Institute for Space Health (TRISH) through NASA cooperative agreement NNX16AO69A, Penn Provost/CHOP Postdoctoral Fellowship for Academic Diversity. A.L.M. is funded by Science Foundation Ireland SFI/19/6628 INSPIRE DMD. C.R. is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. O.S.A. is funded by an MRC Clinical Research Training Fellowship (MR/S021329/1). Y. is supported by a project grant from the British Heart Foundation (PG/20/10270). J.G.Z. is supported by United Kingdom Space Agency\u2014ST/X000036/1 (Walsh). P.S. \u2019s work was funded by NIH\u2014NIDDK grants R01 DK114485, R01 DK129541, and R01 AR080668. S.R. is supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2168), the UK Medical Research Council (CC2168), and the Wellcome Trust (CC2168), and by the Harold J Newman Brain Mapping Foundation. S.B. received NIH OT2TR003450 (SEB, Co-PI), NSF 2033569 (SEB, PI), NSF 2333819 (SEB, PI). A.U. received Grant number 23K10820 from Japan Society for the Promotion of Science (JSPS). M.Y. is supported by space rodent research study for JAXA feasibility experiments using ISS/ Kibo 2015 and 2018 [No grant number]. Grants- in-Aid for Scientific Research from JSPS [grant numbers JSPS 19H05649] and JAXA biorepository multi-omics data program [No grant number]. Almeida, ECA \u2019s NASA Rodent Research 10 Spaceflight experiment supported by a NASA Space Biology Grant NNH14ZTT001N14-14SF. J.C.S. received NIH-R01AG066710 and NIH-R01AG061188. A.J.E. received NIH R01 MH129970 (PI); NIH T32 NS007413 (co-PI); NIH R01 DK135871 (PI: SA Zderic), R01 NS088555 (PI: AM Stowe), R01 NS126279 (PI: Ahrens-Nicklas), R15 MH117628 (PI: K Lambert). S.M.S. and S.R.Z. belong to Biochemical Profile and Nutritional Status Assessment projects and were funded by the NASA Human Research Program\u2019s human Health Countermeasures Element. J.M.G. is supported by the NASA Space Biology Program C.E.M. thanks the Scientific Computing Unit (SCU) at WCM, the WorldQuant and GI Research Foundation, NASA (NNX14AH50G, NNX17AB26G, NNH18ZTT001N-FG2, 80NSSC22K0254, 80NSSC23K0832, the Translational Research Institute through NASA Cooperative Agreement NNX16AO69A), the National Institutes of Health (R01MH117406), and the LLS (MCL7001-18, LLS 9238-16, 7029-23) The NASA Biological & Physical Sciences (BPS) Open Science Data Repository (OSDR) team (S.V.C., L.M.S., S.L.P., R.T.S., L.D., S.G., A.F., A.S.B., V.B., J.M.G.) is primarily funded by the BPS Space Biology Program within the NASA Science Mission Directorate and receive some support from the NASA Human Research Program (HRP). S.V.C. is also funded by NASA HRP grant NNJ16HP24I (P.I. Costes). The OSDR Sample Processing Team (INITIAL) was instrumental generating open science data for numerous tissues from spaceflight missions RR-1, RR-3, RR-7, RR-10, and RR-23. The data supporting this paper can be accessed publicly at osdr.nasa.gov/bio. We would also like to acknowledge the significant role played by the OSDR Analysis Working Groups (AWG) in establishing omics pipeline standards over the past five years. Their collaborative efforts in refining OSDR and analysing multiple datasets have been instrumental in unravelling crucial biological processes occurring in space. Biospecimens utilised in this research were collected by the NASA Space Biology Biospecimen Sharing Program at NASA Ames Research Center (Moffett Field, CA), and awarded to K.S. through the NASA Biological Institutional Scientific Collection (NBISC). Publisher Copyright: © The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.
AB - Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.
UR - http://www.scopus.com/inward/record.url?scp=85195888276&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-49212-1
DO - 10.1038/s41467-024-49212-1
M3 - Article
C2 - 38862484
AN - SCOPUS:85195888276
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4923
ER -