scholarly journals The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

2020 ◽  
Vol 31 (4) ◽  
pp. 716-730 ◽  
Author(s):  
Marc Johnsen ◽  
Torsten Kubacki ◽  
Assa Yeroslaviz ◽  
Martin Richard Späth ◽  
Jannis Mörsdorf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Caloric Restriction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxic Preconditioning ◽  
Preventive Strategies ◽  
Gene Expression Signatures

BackgroundAlthough 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.MethodsTo 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.ResultsThe 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.ConclusionsThis 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/).

Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia–reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide

2018 ◽  
Vol 96 (6) ◽  
pp. 769-776
Author(s):  
Toru Momozane ◽  
Tomohiro Kawamura ◽  
Yumi Itoh ◽  
Masato Sanosaka ◽  
Tsutomu Sasaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Interleukin 6 ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Raw264.7 Cells ◽  
Mrna Levels ◽  
Raw264.7 Macrophages ◽  
Mouse Lungs

Carnosol is a naturally occurring herbal compound, known for its antioxidative properties. We previously found that carnosol protected mouse lungs from ischemia–reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms underpinning carnosol-mediated lung protection, we analyzed modes of interleukin-6 (IL-6) gene expression, which is associated with lung ischemia–reperfusion injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were elevated in the mouse lungs subjected to clamp-reperfusion, which was associated with elevated levels of other inflammatory modulators, such as activating transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein levels in mouse lung homogenates prepared after the clamp-reperfusion. On the other hand, the ATF3 gene expression was negatively correlated with that of IL-6 in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells were subjected to hypoxia–reoxygenation, carnosol treatment lowered oxygen consumption after reoxygenation, which was coupled with a correlation with a transient production of mitochondrial reactive oxygen species and following ATF3 gene expression. These results suggest that carnosol treatment could be a new strategy for protecting lungs from ischemia–reperfusion injury by modulating the ATF3–IL-6 axis.

Abstract 342: Implication Of Mir-98 In The Cardiac Vulnerability Of Pregnancy To Ischemia Reperfusion Injury

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Jingyuan Li ◽  
Zoltan Pierre Arany ◽  
Mansoureh Eghbali
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Late Pregnancy ◽  
Neonatal Rat ◽  
Tunel Staining

We have recently reported that the late-pregnant(LP) rodent is more prone to myocardial ischemia-reperfusion (I/R) injury compared to non-pregnant(NP). However, the underlying molecular mechanisms involved in the higher susceptibility of LP to IR injury are not quite clear. The objective of this study was to investigate the role of miRNA-98(miR-98) in higher cardiac vulnerability to I/R injury in late pregnancy. NP and LP(19 days of pregnancy Sprague-Dawley rats were subjected to 45 min myocardial ischemia followed by 3 hr reperfusion in vivo (I/R group). NP and LP rats which were not subjected to I/R injury served as controls. MicroRNA microarray expression were performed. In vitro, miR-98 was knocked down or overexpressed in neonatal rat ventricular myocytes(NRVMs). Forty eight hour post-transfection, the cells were subjected to 3 hr hypoxia followed by 12 hr reoxygenation. The apoptosis was detected by TUNEL staining, and the western blot was performed to validate the computational predicted targets genes, PGC-1α and STAT3. The miRNA expression profile showed that several miRNAs were differentially expressed in LP sham compared to NP sham, particularly, miR-98 which was significantly upregulated 1.7 fold in LP sham vs NP sham. Interestingly, miR-98 was upregulated even higher (2.3 folds) in LP rats when subjected to ischemia/reperfusion injury compared to NP I/R, suggesting that both ischemia reperfusion and late pregnancy regulate miR-98. Knock down of miRNA-98 in NRVMs significantly reduced apoptosis by ~50%, while over-expression of miR98 resulted in a two fold increase in apoptosis. In-vitro overexpression of miR98-KD in NRVMS resulted in the a significant upregulation of PGC-1α(normalized to scramble control, 1.34±0.04, P<0.05) and STAT3(normalized to scramble control, 1.28±0.05, P<0.05), whereas overexpression of miR-98 resulted in downregulation of both target genes(normalized to scramble control, 0.75±0.02 in PGC-1α; 0.5±0.03 in STAT3, both P<0.05). In conclusion, induction of miR-98 by pregnancy possibly through downregulating PGC-1α and STAT3 may at least in part underlie the greater cardiac vulnerability to I/R injury in late pregnancy.

scholarly journals Identification of hub genes and transcription factor-miRNA-mRNA pathways in mice and human renal ischemia-reperfusion injury

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12375
Author(s):  
Peng Ke ◽  
Lin Qian ◽  
Yi Zhou ◽  
Liu Feng ◽  
Zhentao Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Roc Analysis ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diagnostic Value ◽  
Rna Seq ◽  
Hub Genes ◽  
Renal Ischemia Reperfusion Injury

Background Renal ischemia-reperfusion injury (IRI) is a disease with high incidence rate in kidney related surgery. Micro RNA (miRNA) and transcription factors (TFs) are widely involved in the process of renal IRI through regulation of their target genes. However, the regulatory relationships and functional roles of TFs, miRNAs and mRNAs in the progression of renal IRI are insufficiently understood. The present study aimed to clarify the underlying mechanism of regulatory relationships in renal IRI. Methods Six gene expression profiles were downloaded from Gene Expression Omnibus (GEO). Differently expressed genes (DEGs) and differently expressed miRNAs (DEMs) were identified through RRA integrated analysis of mRNA datasets (GSE39548, GSE87025, GSE52004, GSE71647, and GSE131288) and miRNA datasets (GSE29495). miRDB and TransmiR v2.0 database were applied to predict target genes of miRNA and TFs, respectively. DEGs were applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, followed with construction of protein-protein interaction (PPI) network. Then, the TF-miRNA-mRNA network was constructed. Correlation coefficient and ROC analysis were used to verify regulatory relationship between genes and their diagnostic value in GSE52004. Furthermore, in independent mouse RNA-seq datasets GSE98622, human RNA-seq GSE134386 and in vitro, the expression of hub genes and genes from the network were observed and correlation coefficient and ROC analysis were validated. Results A total of 21 DEMs and 187 DEGs were identified in renal IRI group compared to control group. The results of PPI analysis showed 15 hub genes. The TF-miRNA-mRNA regulatory network was constructed and several important pathways were identified and further verified, including Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd. Four regulatory loops were identified, including Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25. The hub genes and genes in the network showed good diagnostic value in mice and human. Conclusions In this study, we found 15 hub genes and several TF-miRNA-mRNA pathways, which are helpful for understanding the molecular and regulatory mechanisms in renal IRI. Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd were the most important pathways, while Spp1, Fos, Timp1, Tnc, Fosl2 and Junb were the most important hub genes. Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25 might be the negative feedback loops in renal IRI.

scholarly journals Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury—An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies

2021 ◽  
Vol 22 (4) ◽  
pp. 1864
Author(s):  
Norbert Nemeth ◽  
Katalin Peto ◽  
Zsuzsanna Magyar ◽  
Zoltan Klarik ◽  
Gabor Varga ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tissue Perfusion ◽  
Comprehensive Overview ◽  
Hepatic Ischemia ◽  
Continuous Increase ◽  
Ischemic Conditioning ◽  
Stress Dependent

Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular–pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.

scholarly journals The effect of metamizole on ischemia/reperfusion injury in the rat ovary: An analysis of biochemistry, molecular gene expression, and histopathology

2016 ◽  
Vol 48 (1) ◽  
pp. 32 ◽  
Author(s):  
Bahadir Suleyman ◽  
Serkan Kumbasar ◽  
Suleyman Salman ◽  
RagipAtakan Al ◽  
Cengiz Ozturk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Ovary

Ex-vivo perfusion as a successful strategy for reduction of ischemia-reperfusion injury in prolonged muscle flap preservation – A gene expression study

Gene ◽  
2019 ◽  
Vol 701 ◽  
pp. 89-97 ◽  
Author(s):  
Anne Sophie Kruit ◽  
Laura Smits ◽  
Angéle Pouwels ◽  
Marie-Claire J.M. Schreinemachers ◽  
Stefan L.M. Hummelink ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Muscle Flap ◽  
Gene Expression Study ◽  
Expression Study ◽  
Ex Vivo Perfusion ◽  
Successful Strategy

Insight into long noncoding RNA–miRNA–mRNA axes in myocardial ischemia-reperfusion injury: the implications for mechanism and therapy

Epigenomics ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 1733-1748 ◽  
Author(s):  
Wei Xiong ◽  
Yan Qu ◽  
Hongmei Chen ◽  
Jinqiao Qian
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Noncoding Rnas ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Insight Into

Emerging evidence has demonstrated that regulatory noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs) and miRNAs, play crucial roles in the initiation and progress of myocardial ischemia-reperfusion injury (MIRI), which is associated with autophagy, apoptosis and necrosis of cardiomyocytes, as well as oxidative stress, inflammation and mitochondrial dysfunction. LncRNAs serve as a precursor or host of miRNAs and directly/indirectly affecting miRNAs via competitive binding or sponge effects. Simultaneously, miRNAs post-transcriptionally regulate the expression of genes by targeting various mRNA sequences due to their imperfect pairing with mRNAs. This review summarizes the potential regulatory role of lncRNA–miRNA–mRNA axes in MIRI and related molecular mechanisms of cardiac disorders, also provides insight into the potential therapies for MIRI-induced diseases.

Molecular Mechanisms of Renal Ischemic Conditioning Strategies

2015 ◽  
Vol 55 (3) ◽  
pp. 151-183 ◽  
Author(s):  
Casper Kierulf-Lassen ◽  
Gertrude J. Nieuwenhuijs-Moeke ◽  
Nicoline V. Krogstrup ◽  
Mihai Oltean ◽  
Bente Jespersen ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Defense Mechanism ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Clinical Settings ◽  
Ischemic Conditioning ◽  
Protective Signaling ◽  
Survival Mechanisms

Ischemia-reperfusion injury is the leading cause of acute kidney injury in a variety of clinical settings such as renal transplantation and hypovolemic and/or septic shock. Strategies to reduce ischemia-reperfusion injury are obviously clinically relevant. Ischemic conditioning is an inherent part of the renal defense mechanism against ischemia and can be triggered by short periods of intermittent ischemia and reperfusion. Understanding the signaling transduction pathways of renal ischemic conditioning can promote further clinical translation and pharmacological advancements in this era. This review summarizes research on the molecular mechanisms underlying both local and remote ischemic pre-, per- and postconditioning of the kidney. The different types of conditioning strategies in the kidney recruit similar powerful pro-survival mechanisms. Likewise, renal ischemic conditioning mobilizes many of the same protective signaling pathways as in other organs, but differences are recognized.

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