Objective: Endoplasmic reticulum stress (ERS) occurs throughout the pathological process of myocardial ischaemia reperfusion injury (MIRI); however, the key mediators involved in the biological processes of ERS or that can influence the outcomes of ischaemia reperfusion injury (IRI) are unclear. To identify the differentially expressed genes (DEGs) encoding promising mediators in rat hearts in the context of MIRI, gene profiles were mined through transcriptome analysis. Methods: By searching the Gene Expression Omnibus (GEO) database, a suitable GEO dataset was identified in the context of MIRI with 24 h reperfusion after 45 min ischaemia in rats. DEGs were extracted and analysed with R studio, and the properties of those DEGs were elucidated by utilizing protein‒protein-interaction (PPI), Cytoscape, GO and KEGG bioinformatics techniques. The potential hub genes in the first cluster of the DEG dataset were retrieved and verified by basal experiments. Results: By searching the target dataset GSE122020, 1647 mRNAs, including 790 upregulated and 857 downregulated genes, were found in the datasets with criteria of | fold change ≥ 1.2 and p value <0.05. The upregulated and downregulated genes were primarily involved in the “positive regulation of cytokine production”, “regulation of inflammatory response” and “response to pheromone” biological processes. Most of them were mainly correlated with the MAPK, Ras and calcium signalling pathways. In particular, 15 DEGs were found to be involved in the ERS signalling pathways, including Bfar, Itpr1, Srpx, Hspa1b, Usp25, Jun, Casp12, Eif2ak2, Casp4, Trim25, Ifng, Atf3, Hspa1a, Ppp1r15a, and Creb3. Through analysis with the MCODE plugin in Cytoscape, six genes, Atf3, Ppp1r15a, Casp12, Eif2ak2, Ifng, and Hspa1a, were identified as hub genes by the K-means algorithm from Cluster 1. In the in vivo MIRI model, the six genes mentioned above exhibited significant mRNA overexpression in the left anterior descending coronary artery ligation (LAD) model in rats. Conclusions: Altogether, the present study identified six potential DEGs involved in ERS induced by MIRI, which could be therapeutic targets in dealing with IRI-related ERS.
To identify the differentially expressed genes encoding promising inflammatory cytokines in murine lungs in the context of acute lung injury (ALI). Through searching the Gene Expression Omnibus (GEO) databases, three GEO datasets were identified based on the LPS induced animal model within 24hr, differentially expressed genes (DEGs) were extracted and analyzed with R studio, the properties of those DEGs were further analyzed by Protein-Protein-Interaction (PPI), Cytoscape, GO and KEGG bioinformatics techniques as well. The potential hub genes in inflammatory related cluster were retrieved and examined furthermore by basal experiments. By searching, GSE1871, GSE104214, and GSE130936 were screened with a priority of animal model formed in less than 24hr. With a criterion of |log2 fold change (FC)| ≥ 2 and an adjusted P-value < 0.01, 923 DEGs were found altogether in three datasets, eventually 87 overlapped genes were achieved commonly. Most of those DEGs come from anchored component of basal membrane and modulate the cytokine-receptors activity, participating in the regulation of responses to cellular stimuli or cytokine-mediated signaling pathways. Through bioinformatics techniques, 2 clusters were separated by K- means algorithm in 87 DEGs, 20 ranked hub genes were finally concluded. The GO and KEEG enrichment analysis of these 20 genes were highly consistent with previous results except that these hub genes are involved in both virus-related and LPS-related biological processes. For LPS induced in vivo experiment, 7 out of 20 genes exhibited mRNA overexpression under cytokine-cytokine receptors interaction pathway, having a more probability to function in inflammation-related cytokine signaling judging from the predicted transcription factor. Altogether, these findings find out some potential DEGs involved in virus and inflammation related biological process, identified 7 potential hub genes could be the therapeutic target on the cytokine-receptor interaction pathway ground in LPS induced ALI.
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