Identification of significant alteration genes, pathways and TFs induced by LPS in ARDS via bioinformatical analysis

Abstract

Background and aims Acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) is one of the most common acute thoracopathy with complicated pathogenesis in ICU. The study is to explore the differentially expressed genes (DEGs) in the lung tissue and underlying altering mechanisms in ARDS. Methods Gene expression profiles of GSE2411 and GSE130936 were available from GEO database, both of them included in GPL339. Then, an integrated analysis of these genes was performed, including gene ontology (GO) and KEGG pathway enrichment analysis in DAVID database, protein–protein interaction (PPI) network construction evaluated by the online database STRING, Transcription Factors (TFs) forecasting based on the Cytoscape plugin iRegulon, and their expression in varied organs in The Human Protein Atlas. Results A total of 39 differential expressed genes were screened from the two datasets, including 39 up-regulated genes and 0 down-regulated genes. The up-regulated genes were mainly enriched in the biological process, such as immune system process, innate immune response, inflammatory response, and also involved in some signal pathways, including cytokine–cytokine receptor interaction, Salmonella infection, Legionellosis, Chemokine, and Toll-like receptor signal pathway with an integrated analysis. GBP2, IFIT2 and IFIT3 were identified as hub genes in the lung by PPI network analysis with MCODE plug-in, as well as GO and KEGG re-enrichment. All of the three hub genes were regulated by the predictive common TFs, including STAT1, E2F1, IRF1, IRF2, and IRF9. Conclusions This study implied that hub gene GBP2, IFIT2 and IFIT3, which might be regulated by STAT1, E2F1, IRF1, IRF2, or IRF9, played significant roles in ARDS. They could be potential diagnostic or therapeutic targets for ARDS patients.

Identification of the potential cytokines involved in LPS induced acute lung injury in mouse

“…The rst Module with high degree contains genes such as Rsad2, cxcl10, Irf6, I t1, I t3, Cd274, I t2, I 204, Gbp2, Gbp6, Cxcl9, Oasl2, Zbp1 and I 44, which were mostly interferons (IFN-γ) signaling pathway related and downstream proteins. Identical with Lu's study 14 , there were ten genes, such as Cd14, Gbp6, I t1, I t2, Cxcl10, Cxcl1, Cxcl2, I t3, Gbp2 and Rsad2, overlapped with ours. The other module in our study included Il6, Cd14, Cxcl1, Cxcl2, Csf3 and Ccl2, which were primarily LPS induced signaling pathway related in ammatory proteins.…”

Upregulation of FOXO1 contributes to lipopolysaccharide-induced pulmonary endothelial injury by induction of autophagy

“…However, the exact mechanism underlying the effect of LPS on regulating FOXO1 expression remains unknown. Notably, the gene expression of FOXO1 is regulated by 2 transcription factors, E2F transcription factor 1 (E2F-1) and the chromatin factor high-mobility group A1 (HMGA1) (45,46), both of which are known to contribute to LPS-induced inflammatory responses (47,48). These findings let us suggest that LPS might increase FOXO1 expression via E2F-1 and/ or HMGA1-dependent pathways, which merits future investigation.…”

Trimethoprim‐sulfamethoxazole acute respiratory distress syndrome requiring lung transplantation

“…Gene expression analysis using microarray techniques or whole exome sequencing may however be useful tools for the identification of differentially expressed genes involved in the ARDS process. 16 , 17 , 18 Grigoryev et al recently undertook expression‐based genome‐wide association studies (eGWAS) to explore the transcriptional response by lung tissue to injury, discovering 14 new differentially expressed candidate genes associated with ARDS. 17 Lu et al explored lipopolysaccharide induced ARDS in a mouse model finding the most enriched and meaningful biological process terms were mainly involved in immune‐inflammation response functions and pathways linking cytokine‐cytokine receptor interaction.…”

“… 17 Lu et al explored lipopolysaccharide induced ARDS in a mouse model finding the most enriched and meaningful biological process terms were mainly involved in immune‐inflammation response functions and pathways linking cytokine‐cytokine receptor interaction. 16 …”