Transcriptome-Wide Gene Expression in a Murine Model of Ventilator-Induced Lung Injury

Abstract

Background. Mechanical ventilation could lead to ventilator-induced lung injury (VILI), but its underlying pathogenesis remains largely unknown. In this study, we aimed to determine the genes which were highly correlated with VILI as well as their expressions and interactions by analyzing the differentially expressed genes (DEGs) between the VILI samples and controls. Methods. GSE11434 was downloaded from the gene expression omnibus (GEO) database, and DEGs were identified with GEO2R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using DAVID. Next, we used the STRING tool to construct protein-protein interaction (PPI) network of the DEGs. Then, the hub genes and related modules were identified with the Cytoscape plugins: cytoHubba and MCODE. qRT-PCR was further used to validate the results in the GSE11434 dataset. We also applied gene set enrichment analysis (GSEA) to discern the gene sets that had a significant difference between the VILI group and the control. Hub genes were also subjected to analyses by CyTargetLinker and NetworkAnalyst to predict associated miRNAs and transcription factors (TFs). Besides, we used CIBERSORT to detect the contributions of different types of immune cells in lung tissues of mice in the VILI group. By using DrugBank, small molecular compounds that could potentially interact with hub genes were identified. Results. A total of 141 DEGs between the VILI group and the control were identified in GSE11434. Then, seven hub genes were identified and were validated by using qRT-PCR. Those seven hub genes were largely enriched in TLR and JAK-STAT signaling pathways. GSEA showed that VILI-associated genes were also enriched in NOD, antigen presentation, and chemokine pathways. We predicted the miRNAs and TFs associated with hub genes and constructed miRNA-TF-gene regulatory network. An analysis with CIBERSORT showed that the proportion of M0 macrophages and activated mast cells was higher in the VILI group than in the control. Small molecules, like nadroparin and siltuximab, could act as potential drugs for VILI. Conclusion. In sum, a number of hub genes associated with VILI were identified and could provide novel insights into the pathogenesis of VILI and potential targets for its treatment.

New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage

“…In this study, the mRNA expression profile data of cerebral cortex tissue in the HIBD group and control group were extracted, and the relative proportions of 22 immune cells in each cerebral cortical tissue were assessed via CIBERSORT. Referring to the method of Li et al [ 31 ], the LM22 feature matrix will be applied to predict the proportion of immune cells. Moreover, histograms of immune cell proportions, boxplots of immune cell expression, boxplots of immune cell difference analysis, heat map of correlation analysis between immune cells, and heat map of correlations between optimal hub FRDEGs and immune cell infiltration were plotted, respectively.…”