학술논문
Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction
Document Type
Original Paper
Author
Siew, Keith; Nestler, Kevin A.; Nelson, Charlotte; D’Ambrosio, Viola; Zhong, Chutong; Li, Zhongwang; Grillo, Alessandra; Wan, Elizabeth R.; Patel, Vaksha; Overbey, Eliah; Kim, JangKeun; Yun, Sanghee; Vaughan, Michael B.; Cheshire, Chris; Cubitt, Laura; Broni-Tabi, Jessica; Al-Jaber, Maneera Yousef; Boyko, Valery; Meydan, Cem; Barker, Peter; Arif, Shehbeel; Afsari, Fatemeh; Allen, Noah; Al-Maadheed, Mohammed; Altinok, Selin; Bah, Nourdine; Border, Samuel; Brown, Amanda L.; Burling, Keith; Cheng-Campbell, Margareth; Colón, Lorianna M.; Degoricija, Lovorka; Figg, Nichola; Finch, Rebecca; Foox, Jonathan; Faridi, Pouya; French, Alison; Gebre, Samrawit; Gordon, Peter; Houerbi, Nadia; Valipour Kahrood, Hossein; Kiffer, Frederico C.; Klosinska, Aleksandra S.; Kubik, Angela; Lee, Han-Chung; Li, Yinghui; Lucarelli, Nicholas; Marullo, Anthony L.; Matei, Irina; McCann, Colleen M.; Mimar, Sayat; Naglah, Ahmed; Nicod, Jérôme; O’Shaughnessy, Kevin M.; Oliveira, Lorraine Christine De; Oswalt, Leah; Patras, Laura Ioana; Lai Polo, San-huei; Rodríguez-Lopez, María; Roufosse, Candice; Sadeghi-Alavijeh, Omid; Sanchez-Hodge, Rebekah; Paul, Anindya S.; Schittenhelm, Ralf Bernd; Schweickart, Annalise; Scott, Ryan T.; Choy Lim Kam Sian, Terry Chin; da Silveira, Willian A.; Slawinski, Hubert; Snell, Daniel; Sosa, Julio; Saravia-Butler, Amanda M.; Tabetah, Marshall; Tanuwidjaya, Erwin; Walker-Samuel, Simon; Yang, Xiaoping; Yasmin; Zhang, Haijian; Godovac-Zimmermann, Jasminka; Sarder, Pinaki; Sanders, Lauren M.; Costes, Sylvain V.; Campbell, Robert A. A.; Karouia, Fathi; Mohamed-Alis, Vidya; Rodriques, Samuel; Lynham, Steven; Steele, Joel Ricky; Baranzini, Sergio; Fazelinia, Hossein; Dai, Zhongquan; Uruno, Akira; Shiba, Dai; Yamamoto, Masayuki; A.C.Almeida, Eduardo; Blaber, Elizabeth; Schisler, Jonathan C.; Eisch, Amelia J.; Muratani, Masafumi; Zwart, Sara R.; Smith, Scott M.; Galazka, Jonathan M.; Mason, Christopher E.; Beheshti, Afshin; Walsh, Stephen B.
Source
Nature Communications. 15(1)
Subject
Language
English
ISSN
2041-1723
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.
Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.
Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.