Applying a multiscale systems biology approach to study the effect of chronic low-dose exposure to uranium in rat kidneys

Autor: Grison, Stephane, Kereselidze, Dimitri, Cohen, David, Gloaguen, Celine, Elie, Christelle, Lestaevel, Philippe, Legendre, Audrey, Manens, Line, Habchi, Baninia, Benadjaoud, Mohamedamine, Tarlet, Georges, Milliat, Fabien, Martin, Jean-Charles, Lobaccaro, Jean-Marc, Souidi, Maamar
Přispěvatelé: PSE-SANTE/SESANE/LRTOX, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SER/BASEP, DTR/DDMCC/SEARCH, Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), PSE-SANTE/SERAMED, PSE-SANTE/SERAMED/LRMed, GReD, UMR CNRS6293-INSERM U1103, Université Clermont Auvergne (UCA), PSE-SANTE/SERAMED/LRAcc, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Bureau d'analyse et de suivi des expositions professionnelles (IRSN/PSE-SANTE/SER/BASEP), Service d'études et d'expertise en radioprotection (IRSN/PSE-SANTE/SER), Service du partage des connaissances et de l'archivage (IRSN/DTR/DDMCC/SEARCH), Direction Déléguée Management des connaissances et des compétences (IRSN/DTR/DDMCC), Laboratoire de Radiobiologie des expositions médicales (IRSN/PSE-SANTE/SERAMED/LRMed), Service de recherche en radiobiologie et en médecine régénérative (IRSN/PSE-SANTE/SERAMED), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Radiobiologie des expositions accidentelles (IRSN/PSE-SANTE/SERAMED/LRAcc)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: International Journal of Radiation Biology
International Journal of Radiation Biology, Informa Healthcare, 2019, 95 (6), pp.737-752. ⟨10.1080/09553002.2019.1577567⟩
International Journal of Radiation Biology, 2019, 95 (6), pp.737-752. ⟨10.1080/09553002.2019.1577567⟩
ISSN: 0955-3002
1362-3095
DOI: 10.1080/09553002.2019.1577567⟩
Popis: International audience; Purpose: To examine the effects of low-dose exposure to uranium with a systems biology approach, a multiscale high-throughput multi-omics analysis was applied with a protocol for chronic exposure to the rat kidney.Methods: Male and female rats were contaminated for nine months through their drinking water with a nontoxic solution of uranyl nitrate. A multiscale approach enabled clinical monitoring associated with metabolomic and transcriptomic (mRNA and microRNA) analyses.Results: A sex-interaction effect was observed in the kidney, urine, and plasma metabolomes of contaminated rats. Moreover, urine and kidney metabolic profiles correlated and confirmed that the primary dysregulated metabolisms are those of nicotinate-nicotinamide and of unsaturated fatty acid biosynthesis. Upstream of the metabolic pathways, transcriptomic profiles of the kidney reveal gene activity focused on gene regulation mechanisms, cell signaling, cell structure, developmental processes, and cell proliferation. Examination of epigenetic post-transcriptional gene regulation processes showed significant dysregulation of 70 micro-RNAs. The multi-omics approach highlighted the activities of the cells’ biological processes on multiple scales through analysis of gene expression, confirmed by changes observed in the metabolome.Conclusion: Our results showed changes in multi-omic profiles of rats exposed to low doses of uranium contamination, compared with controls. These changes involved gene expression as well as modifications in the transcriptome and the metabolome. The metabolomic profile confirmed that the main molecular targets of uranium in kidney cells are the metabolism of nicotinate-nicotinamide and the biosynthesis of unsaturated fatty acids. Additionally, gene expression analysis showed that the metabolism of fatty acids is targeted by processes associated with cell function. These results demonstrate that multiscale systems biology is useful in elucidating the most discriminative pathways from genomic tometabolomic levels for assessing the biological impact of this low-level environmental exposure, i.e. the exposome.
Databáze: OpenAIRE
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