Department of Anesthesiology, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated with Shandong First Medical University, Jinan 250014, China.
Department of Anesthesiology, Taian City Central Hospital, Taian 271000, China.
Biomed Res Int. 2019 Aug 19;2019:9528584. doi: 10.1155/2019/9528584. eCollection 2019.
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.
尽管经过了 50 多年的临床和基础研究,急性呼吸窘迫综合征(ARDS)仍然是一个全球性的严重挑战,死亡率很高。中性粒细胞激活的严重程度与疾病的严重程度相关。然而,ARDS 中循环多形核中性粒细胞激活的详细病理生理学仍不清楚。为了确定 ARDS 特有的中性粒细胞表型与脓毒症不同的关键途径和基因,从基因表达综合数据库(GEO)中选择了 ARDS 患者(GSE76293)和脓毒症患者(GSE49757)的血液多形核中性粒细胞(PMN)数据集,并使用生物信息学方法进行分析。在 Venn 图中,GSE49757 和 GSE76293 之间有 220 个差异表达基因(DEGs)重叠。通路富集分析结果表明,与 GSE49757 相比,GSE76293 中的 DEGs 主要富集在 MAPK 信号通路、FoxO 信号通路和 AMPK 信号通路中。我们在蛋白质-蛋白质相互作用网络中鉴定出 30 个枢纽基因。通过与 GSE49757 进行比较,我们推测 GAPDH、MAPK8、PIK3CB 和 MMP9 可能在 ARDS 特异性循环中性粒细胞激活的进展中发挥重要作用。这些发现可能为未来开发有希望的 ARDS 诊断和治疗靶点提供新的见解。