Dataset Information

Gene Expression Profiling in Ischemic Postconditioning to Alleviate Mouse Liver Ischemia/Reperfusion Injury.

ABSTRACT: Ischemic postconditioning (IPO) attenuates hepatic ischemia/reperfusion (I/R) injury. However, little is known about the underlying biological pathophysiology, which could be, at least in part, informed by exploring the transcriptomic changes using next-generation RNA sequencing (RNA-Seq). In this study, 18 mice (C57BL/6) were involved and randomly assigned to three groups: normal (n=6), I/R (n=6, subjected to 70% hepatic I/R), and IR+IPO (n=6, applying IPO to mice with I/R injury). We randomly selected 3 mice per group and extracted their liver tissues for next-generation RNA-Seq. We performed a bioinformatics analysis for two comparisons: normal vs. I/R and I/R vs. IR+IPO. From the analysis, 2416 differentially expressed genes (DEGs) were identified (p < 0.05 and fold change ? 1.5). Gene ontology (GO) analysis revealed that these genes were mainly related to cellular metabolic processes, nucleic acids and protein binding processes. The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for the DEGs were the mitogen-activated protein kinase (MAPK), IL-17 signalling pathway, regulating pluripotency of stem cells, and insulin resistance pathway. Validation of 12 selected DEGs by qRT-PCR showed that Cyr61, Atf3, Nr4a1, Gdf15, Osgin1, Egr1, Epha2, Dusp1, Dusp6, Gadd45a and Gadd45b were significantly amplified. Finally, a protein-protein interaction (PPI) network constructed to determine interactions of these 11 DEGs. In summary, by exploring gene expression profiling in regard to hepatic I/R and IPO using next-generation RNA-Seq, we suggested a few progression-related genes and pathways, providing some clues for future experimental research.

SUBMITTER: Zhang P

PROVIDER: S-EPMC6367534 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Gene Expression Profiling in Ischemic Postconditioning to Alleviate Mouse Liver Ischemia/Reperfusion Injury.

Zhang Pengpeng P Ming Yingzi Y Cheng Ke K Niu Ying Y Ye Qifa Q

International journal of medical sciences 20190124 2

Ischemic postconditioning (IPO) attenuates hepatic ischemia/reperfusion (I/R) injury. However, little is known about the underlying biological pathophysiology, which could be, at least in part, informed by exploring the transcriptomic changes using next-generation RNA sequencing (RNA-Seq). In this study, 18 mice (C57BL/6) were involved and randomly assigned to three groups: normal (n=6), I/R (n=6, subjected to 70% hepatic I/R), and IR+IPO (n=6, applying IPO to mice with I/R injury). We randomly ...[more]

PMID: 30745817

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Project description:BackgroundBlood flow restoration is a definitive therapy for salvaging the myocardium following ischemic injury. Nevertheless, the sudden restoration of blood flow to the ischemic myocardium can induce ischemia-reperfusion injury (IRI).ResultsHerein, we investigated the cardioprotective effect of remote ischemic postconditioning (RPostC) through our in vivo rat model of myocardial IRI. The study included three groups: the control group, the IRI group, and the IRI + RPostC group. Ischemia-reperfusion treatment led to an increase in the myocardial infarction area, which was inhibited by RPostC. In contrast to that in the control group, the myocardial apoptosis level was enhanced in the IRI group, whereas RPostC treatment decreased IRI-induced cellular apoptosis. Affymetrix Rat Gene 2.0 ST chip data identified a total of 265 upregulated genes and 267 downregulated genes between the IRI and IRI + RPostC groups. A group of differentially expressed noncoding RNAs (ncRNAs), such as MTA_TC0600002772.mm, MTA_TC1300002394.mm, U7 small nuclear RNA (Rnu7) and RGD7543256_1, were identified. Gene Ontology (GO) enrichment analysis indicated that the positive regulation of some molecular functions, such as GTPase activity, GTP binding, cyclic-nucleotide phosphodiesterase activity and cytokine activity, may contribute to the cardioprotective role of RPostC. Moreover, pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested the potential implication of the TNF signaling pathway and Toll-like receptor signaling pathway. Global signal transduction network analysis, co-expression network analysis and quantitative real-time polymerase chain reaction analysis further identified several core genes, including Pdgfra, Stat1, Lifr and Stfa3.ConclusionRemote ischemic postconditioning treatment can decrease IRI-mediated myocardial apoptosis by regulating multiple processes and pathways, such as GTPase activity, cytokine activity, and the TNF and Toll-like receptor signaling pathways. The potential role of the above ncRNAs and core genes in IRI-induced cardiac damage merits further study as well.

Project description:Ischemic postconditioning (IPoC) has been demonstrated to prevent myocardial ischemia?reperfusion injury (MIRI), but its cardioprotective effect is abrogated by hypercholesterolemia. The aim of the present study was to determine whether lycopene (LP), a type of carotenoid, can restore the cardioprotective effect of IPoC in hypercholesterolemic rats. Male Wistar rats were fed a cholesterol?enriched diet for 12 weeks to establish a hypercholesterolemic model. The rat hearts were isolated and subjected to 30 min ischemia and 60 min reperfusion using a Langendorff apparatus. LP was administered to the rats intraperitoneally for 5 consecutive days prior to ischemia and reperfusion. Myocardial pathological changes, infarct size and cell apoptosis were measured by hematoxylin and eosin, triphenyltetrazolium chloride and TUNEL staining, respectively. The changes in endoplasmic reticulum (ER) stress markers, the reperfusion injury salvage kinase (RISK) pathway and mitochondrial apoptosis?related proteins were detected by western blotting. Overall, the results demonstrated that low?dose LP in combination with IPoC ameliorated myocardial histopathological changes, reduced the infarct size and release of cardiac enzymes, and decreased cardiomyocyte apoptosis in hypercholesterolemic rats, but no beneficial effects were achieved by the same dose of LP or IPoC treatment were used alone. Furthermore, the combination of LP and IPoC inhibited the expression of glucose?regulated protein 78 and C/EBP homologous protein, increased the phosphorylation levels of AKT, ERK1/2 and glycogen synthase kinase?3?, repressed mitochondrial permeability transition pore opening, and reduced the expression of cytochrome c, cleaved caspase?9 and cleaved caspase?3. Collectively, these findings demonstrated that LP can restore the cardioprotective effects of IPoC on MIRI in hypercholesterolemic rats, and this restoration by LP was mediated by inhibition of ER stress and reactivation of the RISK pathway in hypercholesterolemic rat myocardium.

Dataset Information

Gene Expression Profiling in Ischemic Postconditioning to Alleviate Mouse Liver Ischemia/Reperfusion Injury.

Publications

Gene Expression Profiling in Ischemic Postconditioning to Alleviate Mouse Liver Ischemia/Reperfusion Injury.

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