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Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

2024Artigo científico Acesso aberto
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dc.contributor.authorMcDonald, J. Tyson
dc.contributor.authorKim, JangKeun
dc.contributor.authorFarmerie, Lily
dc.contributor.authorJohnson, Meghan L.
dc.contributor.authorTrovao, Nidia S.
dc.contributor.authorArif, Shehbeel
dc.contributor.authorSiew, Keith
dc.contributor.authorTsoy, Sergey
dc.contributor.authorBram, Yaron
dc.contributor.authorPark, Jiwoon
dc.contributor.authorOverbey, Eliah
dc.contributor.authorRyon, Krista
dc.contributor.authorHaltom, Jeffrey
dc.contributor.authorSingh, Urminder
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorZaksas, Victoria
dc.contributor.authorGuarnieri, Joseph W.
dc.contributor.authorTopper, Michael
dc.contributor.authorWallace, Douglas C.
dc.contributor.authorMeydan, Cem
dc.contributor.authorBaylin, Stephen
dc.contributor.authorMeller, Robert
dc.contributor.authorMuratani, Masafumi
dc.contributor.authorPorterfield, D. Marshall
dc.contributor.authorKaufman, Brett
dc.contributor.authorMori, Marcelo A.
dc.contributor.authorWalsh, Stephen B.
dc.contributor.authorSigaudo-Roussel, Dominique
dc.contributor.authorMebarek, Saida
dc.contributor.authorBottini, Massimo
dc.contributor.authorMarquette, Christophe A.
dc.contributor.authorWurtele, Eve Syrkin
dc.contributor.authorSchwartz, Robert E.
dc.contributor.authorGaleano, Diego
dc.contributor.authorMason, Christopher E.
dc.contributor.authorGrabham, Peter
dc.contributor.authorBeheshti, Afshin
dc.date.accessioned2024-07-23T11:33:48Z
dc.date.available2024-07-23T11:33:48Z
dc.date.issued2024
dc.description© The Author(s) 2024. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractOur previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.pt_PT
dc.description.sponsorshipThis work was supported by NASA grant 16-ROSBFP_GL-0005: NNH16ZTT001N-FG Appendix G: Solicitation of Proposals for Flight and Ground Space Biology Research (Award Number: 80NSSC19K0883) and The Translational Research Institute for Space Health through NASA Cooperative Agreement NNX16AO69A (T-0404) awarded to A.B. Orphan gene analysis was supported by National Science Foundation IOS 1546858 awarded to E.S.W. M.A.M. was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (310287/2018-9) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (2021/08354-2). JK was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(RS-2023-00241586). CEM thanks the WorldQuant Foundation, NASA (NNX14AH50G, NNX17AB26G, 80NSSC22K0254, NNH18ZTT001N-FG2), the National Institutes of Health (R01MH117406, P01CA214274, R01CA249054), and the LLS (LLS SCOR-7027-23, LLS SCOR 7029-23). 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 [RP_017_20190306; ST_001_20221128; TF_007_20191202]. 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 license to any Author Accepted Manuscript version arising from this submission.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Commun. 2024 Jun 11;15(1):4825pt_PT
dc.identifier.doi10.1038/s41467-024-48920-ypt_PT
dc.identifier.eissn2041-1723
dc.identifier.urihttp://hdl.handle.net/10451/65410
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://www.nature.com/ncomms/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleSpace radiation damage rescued by inhibition of key spaceflight associated miRNAspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume15pt_PT
person.familyNameEnguita
person.givenNameFrancisco J.
person.identifier173306
person.identifier.ciencia-idB215-8D49-3218
person.identifier.orcid0000-0002-8072-8557
person.identifier.ridA-2347-2009
person.identifier.scopus-author-id6602119231
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationa101dbd4-6bf5-4546-882e-e2596eddb6b4
relation.isAuthorOfPublication.latestForDiscoverya101dbd4-6bf5-4546-882e-e2596eddb6b4

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