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Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction.

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posted on 2024-06-17, 11:47 authored by Keith Siew, Kevin A Nestler, Charlotte Nelson, Viola D'Ambrosio, Chutong Zhong, Zhongwang Li, Alessandra Grillo, Elizabeth R Wan, Vaksha Patel, Eliah Overbey, JangKeun Kim, Sanghee Yun, Michael B Vaughan, Chris Cheshire, Laura Cubitt, Jessica Broni-Tabi, Maneera Yousef Al-Jaber, Valery Boyko, Cem Meydan, Peter Barker, Shehbeel Arif, Fatemeh Afsari, Noah Allen, Mohammed Al-Maadheed, Selin Altinok, Nourdine Bah, Samuel Border, Amanda L Brown, Keith Burling, Margareth Cheng-Campbell, Lorianna M Colón, Lovorka Degoricija, Nichola Figg, Rebecca Finch, Jonathan Foox, Pouya Faridi, Alison French, Samrawit Gebre, Peter Gordon, Nadia Houerbi, Hossein Valipour Kahrood, Frederico C Kiffer, Aleksandra S Klosinska, Angela Kubik, Han-Chung Lee, Yinghui Li, Nicholas Lucarelli, Anthony L Marullo, Irina Matei, Colleen M McCann, Sayat Mimar, Ahmed Naglah, Jérôme Nicod, Kevin M O'Shaughnessy, Lorraine Christine De Oliveira, Leah Oswalt, Laura Ioana Patras, San-Huei Lai Polo, María Rodríguez-Lopez, Candice Roufosse, Omid Sadeghi-Alavijeh, Rebekah Sanchez-Hodge, Anindya S Paul, Ralf Bernd Schittenhelm, Annalise Schweickart, Ryan T Scott, Terry Chin Choy Lim Kam Sian, Willian A da Silveira, Hubert Slawinski, Daniel Snell, Julio Sosa, Amanda M Saravia-Butler, Marshall Tabetah, Erwin Tanuwidjaya, Simon Walker-Samuel, Xiaoping Yang, Yasmin, Haijian Zhang, Jasminka Godovac-Zimmermann, Pinaki Sarder, Lauren M Sanders, Sylvain V Costes, Robert AA Campbell, Fathi Karouia, Vidya Mohamed-Alis, Samuel Rodriques, Steven Lynham, Joel Ricky Steele, Sergio Baranzini, Hossein Fazelinia, Zhongquan Dai, Akira Uruno, Dai Shiba, Masayuki Yamamoto, Eduardo AC Almeida, Elizabeth Blaber, Jonathan C Schisler, Amelia J Eisch, Masafumi Muratani, Sara R Zwart, Scott M Smith, Jonathan M Galazka, Christopher E Mason, Afshin Beheshti, Stephen B Walsh
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.

Funding

Crick (Grant ID: CC2168, Grant title: Rodriques CC2168) Crick (Grant ID: CC1064, Grant title: STP Advanced Sequencing) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics)

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