Identification of Key Pathways and Genes of Acute Respiratory Distress Syndrome Specific Neutrophil Phenotype.

Dong Wang,Yajuan Li,Changping Gu,Yuelan Wang,Mengjie Liu

doi:10.1155/2019/9528584

Abstract

Despite over 50 years of clinical and basic studies, acute respiratory distress syndrome (ARDS) is still a critical challenge with high mortality worldwide. The severity of neutrophil activation was associated with disease severity. However, the detailed pathophysiology of the circulating polymorphonuclear neutrophil activation in ARDS remains unclear. To identify key pathways and genes in the ARDS-specific neutrophil phenotype distinct from sepsis, the datasets of blood polymorphonuclear neutrophils (PMNs) from patients with ARDS (GSE76293) and from sepsis patients (GSE49757) were chosen from the Gene Expression Omnibus (GEO) and analyzed using bioinformatics methods. A total of 220 differential expressed genes (DEGs) were overlapped between GSE49757 and GSE76293 in a Venn diagram. Pathway enrichment analysis results showed that DEGs in GSE76293 were mainly enriched in the MAPK signaling pathway, FoxO signaling pathway, and AMPK signaling pathway relative to GSE49757. We identified 30 hub genes in the protein-protein interaction network. By comparing with GSE49757, we speculated that GAPDH, MAPK8, PIK3CB, and MMP9 may play important roles in the progression of ARDS-specific circulating neutrophil activation. The findings may provide novel insights into the development of promising targets for the diagnosis and treatment of ARDS in the future.

Highlights

Acute respiratory distress syndrome (ARDS) is characterized by diffuse damage of the alveolar-capillary barrier, immune cell infiltration, protein-rich edema fluid in the alveoli, and severe gas-exchange abnormalities
12 ARDS blood Polymorphonuclear neutrophils (PMNs) samples and 12 HVT blood PMNs samples were used for analysis in the dataset GSE76293; 20 PMNs samples stimulated with severe sepsis plasma and 19 PMNs samples stimulated with HVT plasma were selected to verify the ARDSspecific neutrophil phenotype in the dataset GSE49757
There were 971 differential expressed genes (DEGs) in PMNs exposed to severe septic plasma compared with unstimulated controls, including 455 upregulated genes and 516 downregulated genes

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is characterized by diffuse damage of the alveolar-capillary barrier, immune cell infiltration, protein-rich edema fluid in the alveoli, and severe gas-exchange abnormalities. Polymorphonuclear neutrophils (PMNs) are crucial for controlling infections as innate immune system cells [2]. Circulating PMNs become activated and penetrate the alveolarcapillary barrier into the airspaces in the progression of ARDS. PMNs in the alveoli inflammatory microenvironment become further activated to play an important role in phagocytosing pathogens, releasing reactive oxygen species and inducing neutrophil extracellular traps [3,4,5,6]. Activated neutrophils lead to alveolar damage and further loss of lung function. The mechanisms of blood PMNs activation and infiltration in the development of ARDS remain poorly understood

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Results

Conclusion