1. The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury
- Author
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Jannis Mörsdorf, Heike Göbel, Martin Richard Späth, Volker Burst, Thomas Benzing, Bianca Habermann, Janine Altmüller, Marc Johnsen, Roman-Ulrich Müller, Andreas Beyer, Caroline Meharg, Katrin Bohl, Assa Yeroslaviz, Michael Ignarski, Bernhard Schermer, Torsten Kubacki, Universitätsklinikum Köln (Uniklinik Köln), Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, Max planck Institute for Biology of Ageing [Cologne], Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institute for Genetics and CECAD, University of Cologne, and Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB)
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0301 basic medicine ,Male ,Bioinformatics ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,ischemia-reperfusion ,MESH: Ischemic Preconditioning ,Mice ,0302 clinical medicine ,MESH: Hypoxia ,preconditioning ,Gene expression ,MESH: Animals ,Ischemic Preconditioning ,transcriptional profiling ,Acute kidney injury ,General Medicine ,Acute Kidney Injury ,Nephrology ,Reperfusion Injury ,caloric restriction ,medicine.symptom ,MESH: Acute Kidney Injury ,Ischemia ,Biology ,acute renal failure ,03 medical and health sciences ,MESH: Gene Expression Profiling ,MESH: Mice, Inbred C57BL ,medicine ,[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Animals ,RNA, Messenger ,Gene ,MESH: Mice ,MESH: RNA, Messenger ,MESH: Caloric Restriction ,hypoxia ,Gene Expression Profiling ,Hypoxia (medical) ,medicine.disease ,MESH: Male ,Gene expression profiling ,Mice, Inbred C57BL ,030104 developmental biology ,Basic Research ,Ischemic preconditioning ,MESH: Reperfusion Injury ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Reperfusion injury ,030217 neurology & neurosurgery - Abstract
Background Although AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance. Methods To identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury. Results The gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI. Conclusions This comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).
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