Co-expression Analysis Reveals Dysregulated miRNAs and miRNA-mRNA Interactions in the Development of Contrast-induced Acute Kidney Injury
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE130797 | GEO | 2020/04/10
REPOSITORIES: GEO
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Project description: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.
| S-EPMC6629072 | biostudies-literature
Project description:Purpose: The pathogenesis of contrast-induced acute kidney injury (CI-AKI) has not yet been clearly understood. miRNAs are important mediators which normally work by post-transcriptional degradation of target mRNAs. Emerging evidence indicated a number of differentially expressed miRNAs in CI-AKI following intravenous contrast medium injection. However, there exist differences in the pathological mechanisms and incidences of CI-AKI between intravenous and intra-arterial contrast administration. We aimed to investigate the critical roles of dysregulated miRNAs and the correlated mRNAs in the kidney injury following intra-arterial contrast exposure. Methods: Based on a reliable CI-AKI rat model, we sought to investigate the roles of miRNA-mRNA interactions in the kidney injury following intra-arterial contrast exposure using the Illumina Genome Analyzer IIx. Results: In the study, 36 differentially expressed mature miRNAs were identified ( fold change > 1.5 and p value < 0.05) in the kidney of CI-AKI rats (n = 3) compared with controls (n = 3), consisting of 23 up-regulated and 13 down-regulated ones. Bioinformatics analysis revealed that Wnt, TGF-β, and 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. Of which, 6 differential miRNAs and 13 genes were selected for further quantitative real-time polymerase chain reaction validation (n = 6 for each group), and a well correspondence between the 2 techniques was observed. Conclusions: In conclusion, our present study contributes to the first evidence of miRNA-mRNA regulations in the development of kidney injury following an intra-arterial contrast injection route. These novel findings provide insights into the underlying mechanisms of CI-AKI.
2020-04-10 | GSE130796 | GEO
Project description:Purpose:The pathogenesis of contrast-induced acute kidney injury (CI-AKI) has not yet been clearly understood. miRNAs are important mediators which normally work by post-transcriptional degradation of target mRNAs. Emerging evidence indicated a number of differentially expressed miRNAs in CI-AKI following intravenous contrast medium injection. However, there exist differences in the pathological mechanisms and incidences of CI-AKI between intravenous and intra-arterial contrast administration. We aimed to investigate the critical roles of dysregulated miRNAs and the correlated mRNAs in the kidney injury following intra-arterial contrast exposure. Methods:Based on a reliable CI-AKI rat model, we sought to investigate the roles of miRNA-mRNA interactions in the kidney injury following intra-arterial contrast exposure using the Illumina Genome Analyzer IIx. Results:In the study, 36 differentially expressed mature miRNAs were identified ( fold change > 1.5 and p value < 0.05) in the kidney of CI-AKI rats (n = 3) compared with controls (n = 3), consisting of 23 up-regulated and 13 down-regulated ones. Bioinformatics analysis revealed that Wnt, TGF-β, and 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. Of which, 6 differential miRNAs and 13 genes were selected for further quantitative real-time polymerase chain reaction validation (n = 6 for each group), and a well correspondence between the 2 techniques was observed. Conclusions:In conclusion, our present study contributes to the first evidence of miRNA-mRNA regulations in the development of kidney injury following an intra-arterial contrast injection route. These novel findings provide insights into the underlying mechanisms of CI-AKI.
2020-04-10 | GSE130795 | GEO
Project description:Co-expression Analysis Reveals Dysregulated miRNAs and miRNA-mRNA Interactions in the Development of Contrast-induced Acute Kidney Injury [miRNA]
| PRJNA541454 | ENA
Project description:Co-expression Analysis Reveals Dysregulated miRNAs and miRNA-mRNA Interactions in the Development of Contrast-induced Acute Kidney Injury [mRNA]
| PRJNA541455 | ENA
Project description:Co-expression Analysis Reveals Dysregulated miRNAs and miRNA-mRNA Interactions in the Development of Contrast-induced Acute Kidney Injury
| PRJNA541452 | ENA
Project description:AimThe aim of this study was to identify mRNA targets of dysregulated miRNAs through the integrated analysis of miRNA and mRNA expression profiling in pulmonary tuberculosis (PTB) patients versus healthy individuals.Materials & methodsExpression profiles in blood obtained from PTB patients and healthy individuals were analyzed using high-throughput sequencing.ResultsForty-one differentially expressed miRNAs and 2565 mRNAs were obtained. A large number of the differentially expressed mRNAs and miRNAs were related to immune-related pathways, particularly the tuberculosis, phagosome and MAPK signaling pathway. Three hundred and fifty-nine potential target genes were identified for 41 differentially expressed miRNAs. Many of target genes were enriched to phagosome, calcium and insulin signaling pathway.ConclusionThe mRNA-miRNA regulatory networks described here provide new insights for further elucidation of PTB pathogenesis.
| S-EPMC6190256 | biostudies-literature
Project description:Contrast-induced acute kidney injury (CI-AKI) is typically defined by an increase in serum creatinine (SCr) after intravascular administration of contrast medium. Since creatinine is an unreliable indicator for acute changes in kidney function, an early biomarkers for CI-AKI diagnosis is important for initiating therapy.We assessed the hypothesis that circulating microRNAs (miRNAs) could be served as potential biomarkers to early detect CI-AKI.The rat model of acute kidney injury was developed as we previously described. We first detect miRNA profile of plasma and kidney tissue using Agilent microarray platform. 3 miRNA species with > 1.5-fold increase in plasma samples of CI-AKI rats, including miRNA-30a, miRNA-30e and miRNA-188, were selected as candidate miRNAs of potential biomarkers. 24 rats were randomly divided into 2 groups (CI-AKI group and control group), each with 4 subgroups (n=3). Peripheral blood and kidney samples were harvest at 8h after contrast medium/normal saline administration. Total RNA sample from each rat in the same subgroup was combined together as pooled sample for further test. The Agilent microarray platform was adapted to profile the miRNA spectra.
2016-05-14 | E-GEOD-81400 | biostudies-arrayexpress
Project description:The aim of this study was to identify mRNA targets of dysregulated miRNAs through the integrated analysis of miRNA and mRNA expression profiling in men with normal versus impaired spermatogenesis. The expression of mRNAs and miRNAs in testicular tissues obtained from males with non-obstructive azoospermia (NOA, n = 4) or obstructive azoospermia (OA, n = 3) with normal spermatogenesis was analyzed using microarray technology. Some of the most interesting results were validated by real time PCR using samples from the same cohort. Ninety-three miRNAs and 4172 mRNAs were differentially expressed in the NOA and normozoospermic OA patients. In addition to confirming that significantly dysregulated genes and miRNAs play pivotal roles in NOA, promising correlation signatures of these miRNA/mRNA pairs were discovered in this study. The functional classification of the miRNA/mRNA pairs revealed that differentially expressed genes were most frequently associated with spermatogenesis, the cell meiosis, the cell cycle, and the development of secondary male sexual characteristics. This is the first systematic profiling of both mRNA and miRNA in testicular tissues of patients with NOA and OA. Our results indicate that the phenotypic status of NOA is characterized by the dysfunction of normal spermatogenesis when compared with OA or normozoospermic males.
| S-EPMC4310093 | biostudies-other
Project description:ObjectiveAcute kidney injury (AKI) is a global problem due to its high morbidity and mortality. The aim of this study was to identify the key RNAs involved in the ischemia/reperfusion (I/R) or cisplatin (CIS) induced AKI.MethodsGene Expression Omnibus database was used to download the microarray dataset GSE106993, GSE130814 and GSE98622. Differentially expressed lncRNAs (DE-lncRNAs) and DE-mRNAs were identified in I/R and CIS induced AKI. The target miRNAs of DE lncRNAs were predicted from miRDB, and the miRNA of lncRNA target mRNAs were predicted form StarBase dataset. The ceRNA regulatory networks, GO and KEGG enrichment analysis, and protein-protein interaction (PPI) of I/R and CIS induced AKI specific genes were constructed. The CIBESORT was applied to infer the proportion of 22 immune infiltration cells based on gene expression profiles of I/R and CIS induced AKI.ResultsTotally, 2 DE-lncRNAs and 375 DE-mRNAs were identified in I/R and CIS induced AKI. The common ceRNA network was constructed between CIS group and I/R induced AKI group, which contained 2 lncRNAs (Platr7 and Gm15611), 65 mmu-miRNAs and 167 mRNAs. The 167 common mRNAs were enriched in the biological process of transcription regulation, metabolic process, cell proliferation, the cellular component (CC) of extracellular region and space, the molecular function of DNA binding, and transcription regulator activity in CIS and IRI induced AKI. The common 167 mRNAs involved in the MAPK signaling pathway and JAK-STAT signaling pathway were identified. Protein-Protein Interaction (PPI) Network of ceRNAs network expressed gene was constructed, including 81 nodes, which contained 3 upregulated genes and 78 downregulated genes. Among them, mitochondrial apoptosis-related genes Pmaip1 and Nptx1 showed significantly high expression in the GSE98622 and GSE106993 data sets. The investigation to the connection between the gene expression profiles and immune cell infiltration showed considerable differences in immune cell percentage between AKI group and normal group.ConclusionNovel lncRNAs and mRNAs were identified, which may serve as potential biomarkers to predict the diagnostic and therapeutic targets for AKI patients based on a large-scale sample. More importantly, the ceRNA network of I/R or CIS induced AKI was constructed, which provides valuable information to further explore the molecular mechanism underlying onset and progression of AKI.
| S-EPMC10579013 | biostudies-literature