Johnsen, Marc, Kubacki, Torsten, Yeroslaviz, Assa, Spaeth, Martin Richard, Moersdorf, Jannis, Gobel, Heike, Bohl, Katrin, Ignarski, Michael ORCID: 0000-0001-6057-7694, Meharg, Caroline, Habermann, Bianca ORCID: 0000-0002-2457-7504, Altmueller, Janine, Beyer, Andreas ORCID: 0000-0002-3891-2123, Benzing, Thomas, Schermer, Bernhard, Burst, Volker and Mueller, Roman-Ulrich (2020). The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury. J. Am. Soc. Nephrol., 31 (4). S. 716 - 731. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1533-3450

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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/).

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Johnsen, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kubacki, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yeroslaviz, AssaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spaeth, Martin RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moersdorf, JannisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gobel, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bohl, KatrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ignarski, MichaelUNSPECIFIEDorcid.org/0000-0001-6057-7694UNSPECIFIED
Meharg, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Habermann, BiancaUNSPECIFIEDorcid.org/0000-0002-2457-7504UNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyer, AndreasUNSPECIFIEDorcid.org/0000-0002-3891-2123UNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burst, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Roman-UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-338503
DOI: 10.1681/ASN.2019050534
Journal or Publication Title: J. Am. Soc. Nephrol.
Volume: 31
Number: 4
Page Range: S. 716 - 731
Date: 2020
Publisher: AMER SOC NEPHROLOGY
Place of Publication: WASHINGTON
ISSN: 1533-3450
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACUTE KIDNEY INJURY; CALORIC RESTRICTION; DIETARY RESTRICTION; PROMOTING HEALTH; KEY REGULATOR; CELL INJURY; HYPOXIA; PATHWAY; DEFICIENCY; METABOLISMMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33850

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