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      Co-expression analysis reveals dysregulated miRNAs and miRNA-mRNA interactions in the development of contrast-induced acute kidney injury

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          Abstract

          The pathogenesis of contrast-induced acute kidney injury (CI-AKI) is incompletely understood. MicroRNAs (miRNAs) are important mediators that normally function via post-transcriptional degradation of target mRNAs. Emerging evidence indicates the appearance of differentially expressed (DE) miRNAs in CI-AKI following the injection of intravenous contrast medium. However, there are differences in the pathological mechanism and incidence of CI-AKI between intravenous and intra-arterial contrast administration. The present study aimed to investigate the critical roles of dysregulated miRNAs and their associated mRNAs in kidney injury following intra-arterial contrast medium exposure. Based on a reliable CI-AKI rat model, we conducted genome-wide miRNA and mRNA expression profiling analysis using deep sequencing. In the study, 36 DE mature miRNAs were identified (fold change > 1.5 and p value < 0.05) in the kidneys of CI-AKI rats (n = 3) compared with that in the controls (n = 3), consisting of 23 up-regulated and 13 down-regulated DE miRNAs. Bioinformatic analysis revealed that wingnut (Wnt), transforming growth factor beta (TGF-β), and 5'-AMP-activated protein kinase (AMPK) signaling pathways were most likely to be modulated by these dysregulated miRNAs. Around 453 dysregulated genes (fold change > 2.0 and p value < 0.05) were identified. Integrated analysis revealed 2037 putative miRNA-mRNA pairs with negative correlations. Among them, 6 DE miRNAs and 13 genes were selected for further quantitative real-time reverse transcription polymerase chain reaction validation (n = 6 for each group), and a good correspondence between the two techniques was observed. In conclusion, the present study provided evidence of miRNA-mRNA interactions in the development of kidney injury following an intra-arterial contrast injection. These findings provide insights into the underlying mechanisms of CI-AKI.

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          Gene Ontology: tool for the unification of biology

          Michael Ashburner, Catherine A. Ball, Judith Blake … (2002)
          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.

            Roxana Mehran, Eve Aymong, Eugenia Nikolsky … (2004)
            We sought to develop a simple risk score of contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI). Although several risk factors for CIN have been identified, the cumulative risk rendered by their combination is unknown. A total of 8,357 patients were randomly assigned to a development and a validation dataset. The baseline clinical and procedural characteristics of the 5,571 patients in the development dataset were considered as candidate univariate predictors of CIN (increase >or=25% and/or >or=0.5 mg/dl in serum creatinine at 48 h after PCI vs. baseline). Multivariate logistic regression was then used to identify independent predictors of CIN with a p value 75 years, anemia, and volume of contrast) were assigned a weighted integer; the sum of the integers was a total risk score for each patient. The overall occurrence of CIN in the development set was 13.1% (range 7.5% to 57.3% for a low [ or=16] risk score, respectively); the rate of CIN increased exponentially with increasing risk score (Cochran Armitage chi-square, p < 0.0001). In the 2,786 patients of the validation dataset, the model demonstrated good discriminative power (c statistic = 0.67); the increasing risk score was again strongly associated with CIN (range 8.4% to 55.9% for a low and high risk score, respectively). The risk of CIN after PCI can be simply assessed using readily available information. This risk score can be used for both clinical and investigational purposes.
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              Mitochondrial energetics in the kidney

              Pallavi Bhargava, Rick G. Schnellmann (2017)
              Mitochondria provide the kidney with energy to remove waste from the blood and regulate fluid and electrolyte balance. This Review discusses how mitochondrial homeostasis is maintained, the changes in mitochondrial energetics that occur in acute kidney injury and diabetic nephropathy, and how targeting mitochondrial energetics might aid the treatment of renal disease.
              Article 0 comments Cited 419 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Zhiqing Wang:
                ORCID: http://orcid.org/0000-0003-4210-3748
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: Writing – original draft
                Weiwei Bao: Role: Data curationRole: Investigation
                Xiaobiao Zou: Role: Data curationRole: Investigation
                Ping Tan: Role: ConceptualizationRole: Funding acquisition
                Hao Chen: Role: Investigation
                Cancan Lai: Role: Investigation
                Donglin Liu: Role: Investigation
                Zhurong Luo: Role: ConceptualizationRole: Project administration
                Mingfang Huang: Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: Writing – review & editing
                Kathrin Eller: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 15 July 2019
                Publication date Collection: 2019
                Volume: 14
                Issue: 7
                Electronic Location Identifier: e0218574
                Affiliations
                [1 ] Department of Cardiology, 900 Hospital of the Joint Logistics Team, Fujian Medical University, Fuzhou, China
                [2 ] Faculty of Graduate Studies, Bengbu Medical College, Bengbu, China
                [3 ] Department of Cadre Health Care, 900 Hospital of the Joint Logistics Team, Fujian Medical University, Fuzhou, China
                Medizinische Universitat Graz, AUSTRIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-4210-3748
                Article
                Publisher ID: PONE-D-19-05007
                DOI: 10.1371/journal.pone.0218574
                PMC ID: 6629072
                PubMed ID: 31306435
                SO-VID: a7b5aebd-2890-4486-b6a6-a9905b65e425
                Copyright © © 2019 Wang et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 20 February 2019
                Date accepted : 4 June 2019
                Page count
                Figures: 7, Tables: 2, Pages: 19
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003392, Natural Science Foundation of Fujian Province;
                Award ID: 2016J01477
                Award Recipient :
                Funded by: the Outstanding Youth Science Fund Project of No. 900 Hospital of Chinese PLA
                Award ID: 2015Q08
                Award Recipient :
                ORCID: http://orcid.org/0000-0003-4210-3748
                Funded by: the Health Care Project of Chinese PLA
                Award ID: 16BJZ55
                Award Recipient :
                This work was supported by The Natural Science Foundation of Fujian province (Mingfang Huang: Grant number 2016J01477, URL: http://xmgl.fjkjt.gov.cn/showManageMainPage.do); The Outstanding Youth Science Fund Project of No. 900 Hospital of Chinese PLA (Zhiqing Wang: Grant number 2015Q08, a URL is not avaliable); and The Health Care Project of Chinese PLA (Ping Tan: Grant number 16BJZ55,a URL is not avaliable). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and life sciences
                Subject: Biochemistry
                Subject: Nucleic acids
                Subject: RNA
                Subject: Non-coding RNA
                Subject: Natural antisense transcripts
                Subject: MicroRNAs
                Subject: Biology and life sciences
                Subject: Genetics
                Subject: Gene expression
                Subject: Gene regulation
                Subject: MicroRNAs
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Renal System
                Subject: Kidneys
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Renal System
                Subject: Kidneys
                Subject: Biology and life sciences
                Subject: Molecular biology
                Subject: Molecular biology techniques
                Subject: Sequencing techniques
                Subject: RNA sequencing
                Subject: Research and analysis methods
                Subject: Molecular biology techniques
                Subject: Sequencing techniques
                Subject: RNA sequencing
                Subject: Biology and life sciences
                Subject: Biochemistry
                Subject: Nucleic acids
                Subject: RNA
                Subject: Non-coding RNA
                Subject: Small nuclear RNA
                Subject: Small nucleolar RNA
                Subject: Biology and life sciences
                Subject: Genetics
                Subject: Gene expression
                Subject: Gene regulation
                Subject: Small nucleolar RNA
                Subject: Biology and Life Sciences
                Subject: Genetics
                Subject: Gene Expression
                Subject: Biology and life sciences
                Subject: Biochemistry
                Subject: Nucleic acids
                Subject: RNA
                Subject: Messenger RNA
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogenesis
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Signal Transduction
                Subject: Cell Signaling
                Subject: Signaling Cascades
                Subject: WNT Signaling Cascade
                Custom metadata
                Data Availability All relevant data are within the manuscript and its Supporting Information files. In addition, we have deposited the laboratory protocols to protocols.io ( http://dx.doi.org/10.17504/protocols.io.dx.doi.org/10.17504/protocols.io.z6bf9 an). The next-generation sequencing data associated with our study have been submitted to Gene Expression Omnibus (accession number: GSE130795 for mRNA and GSE130796 for miRNA).

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                ScienceOpen disciplines: Uncategorized

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