Whole Transcriptomic Analysis of Key Genes and Signaling Pathways in Endogenous ARDS.
To analyze the differentially expressed genes (DEGs) in rats with endogenous acute respiratory distress syndrome (ARDS) lung injury and explore the pathogenesis and early diagnostic molecular markers using whole transcriptomic data.
Twelve 8-week-old male Sprague Dawley rats were selected and randomly and equally divided into ARDS lung injury group and normal control group. RNA was extracted from the left lung tissues of both the groups and sequenced using the paired-end sequencing mode of the Illumina Hiseq sequencing platform. The DEGs of miRNA, cirRNA, lncRNA, and mRNA were screened using DESeq2 software, and the ceRNA regulatory network was constructed using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the mRNA DEGs. STRING and Cytoscape software were used to construct the protein interaction network and identify the 15 key genes, which were verified using quantitative real-time polymerase chain reaction (qRT-PCR).
Based on different screening conditions, and compared with the control group, the ARDS lung injury group showed 836 mRNA DEGs (386 upregulated and 450 downregulated), 110 lncRNA DEGs (53 upregulated and 57 downregulated), 19 circRNA DEGs (3 upregulated and 16 downregulated), and 6 miRNA DEGs (5 upregulated and 1 downregulated gene). GO showed that the DEGs of mRNA were mainly involved in biological processes, such as defense response to lipopolysaccharide and other organisms, leukocyte chemotaxis, neutrophil chemotaxis, and cytokine-mediated signaling. KEGG enrichment analysis showed that the DEGs played their biological roles mainly by participating in IL-17, TNF, and chemokine signaling pathways. The PPI analysis showed a total of 281 node proteins and 634 interaction edges. The top 15 key genes, which were screened, included Cxcl10, Mx1, Irf7, Isg15, Ifit3, Ifit2, Rsad2, Ifi47, Oasl, Dhx58, Usp18, Cmpk2, Herc6, Ifit1, and Gbp4. The ceRNA network analysis showed 69 nodes and 73 correlation pairs, where the key gene nodes were miR-21-3p, Camk2g, and Stx2.
The chemotaxis, migration, and degranulation of inflammatory cells, cytokine immune response, autophagy, and apoptosis have significant biological functions in the occurrence and development of endogenous acute lung injury during ARDS. Thus, the camk2g/miR-21-3p/lncRNA/circRNA network, CXCL10/CXCR3, and IL-17 signaling pathways might provide novel insights and targets for further studying the lung injury mechanism and clinical treatment.
Xie Y
，Luo J
，Hu W
，Ye C
，Ren P
，Wang Y
，Li X
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Identification of potential immune/diagnosis related gene-immunocyte subtype networks in extracellular immune response to respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) is one of the important pathogenic agents of pediatric respiratory tract infection. Weighted gene co-expression network analysis (WGCNA) is used to study autoimmune diseases, which can find potential hub genes. The diagnostic model based on hub genes and machine learning makes it possible to diagnose the extracellular immune response to RSV infection early.
The aim of the present study was to identify potential immune, diagnose and treatment related genes expressed in RSV-infected cells.
Firstly, gene expression data were downloaded from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). Secondly, WGCNA was performed based on DEGs to obtain hub genes related to immunity score. Thirdly, protein-protein interaction (PPI) and the immune infiltration analysis of hub immune related genes were performed. Finally, diagnostic and immune related genes were identified by machine learning, followed by functional analysis.
Totally, 2063 DEGs were identified in the extracellular immune response to RSV infection. Among which, 10 key immune and diagnosis related genes were identified, including ITGA2B, GP9, ITGB3, SELP, PPBP, MPL, CXCL8, NFE2, PTGS1 and LY6G6F. Several immune/diagnosis related gene-immunocyte subtype networks were identified, such as CXCL8-Type 17 T helper cell, LY6G6F-CD56 bright natural killer cell, PPBP-activated CD4 T cell/T follicular helper cell, NFE2/PTGS1/SELP-activated dendritic cell, GP9/ITGA2B/MPL-activated CD8 T cell. ITGB3, MPL and PTGS1 could be considered as therapeutic targets. Some significantly enriched signaling pathways were identified, including hematopoietic cell lineage (involving GP9 and ITGA2B), cytokine-cytokine receptor interaction (involving MPL), chemokine signaling pathway (involving PPBP) and arachidonic acid metabolism (involving PTGS1).
The 10-immune related gene signature may be used as potential diagnostic markers for the extracellular immune response to RSV infection, which may provide a new field in searching for diagnostic and therapeutic molecules in the extracellular immune response to RSV infection.
Wang B
，Liu H
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ResearchGate
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钛学术
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