Integrated bioinformatics analysis of retinal ischemia/reperfusion injury in rats with potential key genes
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SUBMITTER: Qing K
PROVIDER: S-EPMC11017533 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC10967080 | biostudies-literature
Project description:BackgroundHepatic ischemia-reperfusion injury (HIRI) is an unavoidable surgical complication after liver transplantation, but current HIRI treatments cannot achieve satisfactory clinical outcomes. Thus, safer and more effective prevention and treatment methods need to be explored.MethodsTranscriptome messenger ribonucleic acid (mRNA) and long non-coding RNA (lncRNA) sequencing data were obtained from male Sprague-Dawley rats, and these data were used to identify the differentially expressed genes (DEGs) and differentially expressed lncRNAs (DE-lncRNAs) between the HIRI and control samples. A protein-protein interaction (PPI) network was also constructed for the DE-mRNAs to identify candidate genes, and the receiver operating characteristic curves of the 21 candidate genes were plotted to evaluate the diagnostic value of the candidate genes for HIRI. A random forest (RF) model, support vector machine model and generalized linear model were constructed based on the candidate genes. A gene set enrichment analysis (GSEA) of the key genes was conducted to determine the enriched pathways in the high expression groups. The miRWalk and miRanda database were used to constructed the lncRNA-miRNA-mRNA network. Finally, the expressions of the key genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsA total of 256 DEGs and 67 DE-lncRNAs were identified in the HIRI and control samples. To explore the interactions between the DE-mRNAs, a PPI network of 130 DEGs was constructed. Further, 21 genes were selected as the candidate genes. Subsequently, 6 genes [i.e., Keratin-14 (Krt14), Uroplakin 3B (Upk3b), Keratin 7 (Krt7), Cadherin 3 (Cdh3), mesothelin (Msln), and Glypican 3 (Gpc3)] in the RF model were defined as the key genes. The GSEA results indicated that these key genes were enriched in the terms of extracellular structure organization, and extracellular matrix organization. Moreover, a lncRNA-miRNA-mRNA network was constructed with 4 lncRNAs, 5 mRNAs, and 11 miRNAs. Finally, the results indicated that the expression of Krt14, Upk3b, Msln, and Gpc3 were more highly expressed in the control samples than the HIRI samples.ConclusionsA total of 6 key genes (i.e., Krt14, Upk3b, Krt7, Cdh3, Msln, and Gpc3) were identified. Our findings provide novel ideas for the diagnosis and treatment of HIRI.
| S-EPMC9843403 | biostudies-literature
Project description:BackgroundMyocardial ischemia-reperfusion injury (MIRI) has become a thorny and unsolved clinical problem. The pathological mechanisms of MIRI are intricate and unclear, so it is of great significance to explore potential hub genes and search for some natural products that exhibit potential therapeutic efficacy on MIRI via targeting the hub genes.MethodsFirst, the differential expression genes (DEGs) from GSE58486, GSE108940, and GSE115568 were screened and integrated via a robust rank aggregation algorithm. Then, the hub genes were identified and verified by the functional experiment of the MIRI mice. Finally, natural products with protective effects against MIRI were retrieved, and molecular docking simulations between hub genes and natural products were performed.Results230 integrated DEGs and 9 hub genes were identified. After verification, Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be the most significant genes during MIRI. A total of 75 natural products were discovered. Most of them (especially araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) showed good ability to bind the hub genes.ConclusionsEmr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be critical in the pathological process of MIRI, and the natural products (araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) targeting these hub genes exhibited potential therapeutic efficacy on MIRI. Our findings provided new insights to explore the mechanism and treatments for MIRI and revealed new therapeutic targets for natural products with protective properties against MIRI.
| S-EPMC9033367 | biostudies-literature
Project description:Background: Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death worldwide in 2020, and it ranks fifth in global incidence. Liver resection or liver transplantation are the two most prominent surgical procedures for treating primary liver cancer. Both inevitably result in HIRI, causing severe complications for patients and affecting their prognosis and quality of survival. Ferroptosis, a newly discovered mode of cell death, is closely related to HIRI. We used bioinformatics analysis to explore the relationship between the two further. Methods: The GEO database dataset GSE112713 and the FerrDB database data were selected to use bioinformatic analysis methods (difference analysis, FRGs identification, GO analysis, KEGG analysis, PPI network construction and analysis, Hub gene screening with GO analysis and KEGG analysis, intergenic interaction prediction, drug-gene interaction prediction, miRNA prediction) for both for correlation analysis. The GEO database dataset GSE15480 was selected for preliminary validation of the screened Hub genes. Results: We analysed the dataset GSE112713 for differential gene expression before and after hepatic ischemia-reperfusion and identified by FRGs, yielding 11 genes. These 11 genes were subjected to GO, and KEGG analyses, and PPI networks were constructed and analysed. We also screened these 11 genes again to obtain 5 Hub genes and performed GO analysis, KEGG analysis, intergenic interaction prediction, drug-gene interaction prediction, and miRNA prediction on these 5 Hub genes. Finally, we obtained preliminary validation of all these 5 Hub genes by dataset GSE15480. Conclusion: There is a close relationship between HIRI and ferroptosis, and inhibition of ferroptosis can potentially be a new approach to mitigate HIRI treatment in the future.
| S-EPMC9755192 | biostudies-literature
Project description:BackgroundWith the intensification of population aging, the proportion of aging livers in the donor pool is increasing rapidly. Compared with young livers, aging livers are more susceptible to ischemia-reperfusion injury (IRI) during liver transplantation, which greatly affects the utilization rate of aging livers. The potential risk factors associated with IRI in aging livers have not been fully elucidated.MethodsIn this work, five human liver tissue expression profiling datasets (GSE61260, GSE107037, GSE89632, GSE133815, and GSE151648) and a total of 28 young and aging liver tissues of human (N = 20) and mouse (N = 8) were used to screen and verify the potential risk factors associated with aging livers being more prone to IRI. DrugBank Online was used to screen drugs with potential to alleviate IRI in aging livers.ResultsThe gene expression profile and immune cell composition between young and aging livers had significant differences. Among the differentially expressed genes, aryl hydrocarbon receptor nuclear translocator-like (ARNTL), BTG antiproliferation factor 2 (BTG2), C-X-C motif chemokine ligand 10 (CXCL10), chitinase 3-like 1 (CHI3L1), immediate early response 3 (IER3), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PPARGC1A), mainly involved in the regulation of cell proliferation, metabolism, and inflammation, were also dysregulated in liver tissues suffered from IRI and could form a FOS-centered interaction network. Nadroparin was screened out with the potential to target FOS in DrugBank Online. In addition, the proportion of dendritic cells (DCs) was significantly upregulated in aging livers.ConclusionsWe combined the expression profiling datasets of liver tissues and samples collected in our hospital for the first time to reveal that the changes in the expression of ARNTL, BTG2, CXCL10, CHI3L1, IER3, FOS, and PPARGC1A and the proportion of dendritic cells may be associated with aging livers being more prone to IRI. Nadroparin may be used to mitigate IRI in aging livers by targeting FOS, and regulation of DC activity may also reduce IRI.
| S-EPMC9949953 | biostudies-literature
Project description:BackgroundRetinal function is ordered by interactions between transcriptional and posttranscriptional regulators at the molecular level. These regulators include transcription factors (TFs) and posttranscriptional factors such as microRNAs (miRs). Some studies propose that miRs predominantly target the TFs rather than other types of protein coding genes and such studies suggest a possible interconnection of these two regulators in co-regulatory networks.ResultsOur lab has generated mRNA and miRNA microarray expression data to investigate time-dependent changes in gene expression, following induction of ischemia-reperfusion (IR) injury in the rat retina. Data from different reperfusion time points following retinal IR-injury were analyzed. Paired expression data for miRNA-target gene (TG), TF-TG, miRNA-TF were used to identify regulatory loop motifs whose expressions were altered by the IR injury paradigm. These loops were subsequently integrated into larger regulatory networks and biological functions were assayed. Systematic analyses of the networks have provided new insights into retinal gene regulation in the early and late periods of IR. We found both overlapping and unique patterns of molecular expression at the two time points. These patterns can be defined by their characteristic molecular motifs as well as their associated biological processes. We highlighted the regulatory elements of miRs and TFs associated with biological processes in the early and late phases of ischemia-reperfusion injury.ConclusionsThe etiology of retinal ischemia-reperfusion injury is orchestrated by complex and still not well understood gene networks. This work represents the first large network analysis to integrate miRNA and mRNA expression profiles in context of retinal ischemia. It is likely that an appreciation of such regulatory networks will have prognostic potential. In addition, the computational framework described in this study can be used to construct miRNA-TF interactive systems networks for various diseases/disorders of the retina and other tissues.
| S-EPMC4424502 | biostudies-literature
Project description:Transcriptional profiling of rat gracilis muscle after ischemia 4h and reperfusion for 1d, 3d, 7d and 14d v.s. sham control, and correlate the downregulated transcripts to the computational predicted gene targets of ron-miR-21 Following 4 h of ischemia and subsequent reperfusion for 4 h of the gracilis muscles, three miRNAs (miR-21, miR-200c, and miR-205) of 350 tested rat miRNAs were found to have an increased expression in the miRNA array.The expression of the mRNA in the muscle specimens after 4 h of ischemia and reperfusion for 1, 3, 7, and 14 d were detected with the Agilent Whole Rat Genome 4 Ã 44 k oligo microarray. A combined approach using a computational prediction algorithm that included miRanda, PicTar, TargetScanS, MirTarget2, RNAhybrid, and the whole genome microarray experiment was performed by monitoring the mRNA:miRNA association to identify potential target genes. Four-condition experiment, Gracilis muscle after ischemia-reperfusion injury for 1d, 3d, 7d and 14d v.s.Gracilis muscle (sham control), Biological replicates: 1 control replicate, 1 experiement replicate (each condition).
2010-05-07 | E-GEOD-21406 | biostudies-arrayexpress
Project description:BackgroundIschemia-reperfusion injury (IRI) remains an inevitable and major challenge in renal transplantation. The current study aims to obtain deep insights into underlying mechanisms and seek prognostic genes as potential therapeutic targets for renal IRI (RIRI).MethodsAfter systematically screening the Gene Expression Omnibus (GEO) database, we collected gene expression profiles of over 1,000 specimens from 11 independent cohorts. Differentially expressed genes (DEGs) were identified by comparing allograft kidney biopsies taken before and after reperfusion in the discovery cohort and further validated in another two independent transplant cohorts. Then, graft survival analysis and immune cell analysis of DEGs were performed in another independent renal transplant cohort with long-term follow-ups to further screen out prognostic genes. Cell type and time course analyses were performed for investigating the expression pattern of prognostic genes in more dimensions utilizing a mouse RIRI model. Finally, two novel genes firstly identified in RIRI were verified in the mouse model and comprehensively analyzed to investigate potential mechanisms.ResultsTwenty DEGs upregulated in the process of RIRI throughout different donor types (living donors, cardiac and brain death donors) were successfully identified and validated. Among them, upregulation of 10 genes was associated with poor long-term allograft outcomes and exhibited strong correlations with prognostic immune cells, like macrophages. Furthermore, certain genes were found to be only differentially expressed in specific cell types and remained with high expression levels even months after RIRI in the mouse model, which processed the potential to serve as therapeutic targets. Importantly, two newly identified genes in RIRI, Btg2 and Rhob, were successfully confirmed in the mouse model and found to have strong connections with NF-κB signaling.ConclusionsWe successfully identified and validated 10 IRI-associated prognostic genes in renal transplantation across different donor types, and two novel genes with crucial roles in RIRI were recognized for the first time. Our findings offered promising potential therapeutic targets for RIRI in renal transplantation.
| S-EPMC8452995 | biostudies-literature
Project description:Transcriptional profiling of rat gracilis muscle after ischemia 4h and reperfusion for 1d, 3d, 7d and 14d v.s. sham control, and correlate the downregulated transcripts to the computational predicted gene targets of ron-miR-21 Following 4 h of ischemia and subsequent reperfusion for 4 h of the gracilis muscles, three miRNAs (miR-21, miR-200c, and miR-205) of 350 tested rat miRNAs were found to have an increased expression in the miRNA array.The expression of the mRNA in the muscle specimens after 4 h of ischemia and reperfusion for 1, 3, 7, and 14 d were detected with the Agilent Whole Rat Genome 4 × 44 k oligo microarray. A combined approach using a computational prediction algorithm that included miRanda, PicTar, TargetScanS, MirTarget2, RNAhybrid, and the whole genome microarray experiment was performed by monitoring the mRNA:miRNA association to identify potential target genes.
2010-04-22 | GSE21406 | GEO
Project description:Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which could induce the poor prognosis. The purpose of this study was to characterize the molecular mechanism of the functional changes of CDllb+/Ly6Cintermediate macrophages after renal IRI. The gene expression profiles of CDllb+/Ly6Cintermcdiate macrophages of the sham surgery mice, and the mice 4 h, 24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database. Analysis of mRNA expression profiles was conducted to identify differentially expressed genes (DEGs), biological processes and pathways by the series test of cluster. Protein-protein interaction network was constructed and analysed to discover the key genes. A total of 6738 DEGs were identified and assigned to 20 model profiles. DEGs in profile 13 were one of the predominant expression profiles, which are involved in immune cell chemotaxis and proliferation. Signet analysis showed that Atp5al, Atp5o, Cox4i, Cdc42, Rac2 and Nhp2 were the key genes involved in oxidation-reduction, apoptosis, migration, M1-M2 differentiation, and proliferation of macrophages. RPS18 may be an appreciate reference gene as it was stable in macrophages. The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD 1lb+Ly6Cintermediate macrophages after renal IRI. Moreover, the vital gene Nhp2 may involve the polarization of macrophages, which may be a new target to affect the process of AKI.
| S-EPMC7089064 | biostudies-literature