Potential biomarkers for inflammatory response in acute lung injury.

Abstract

Acute lung injury (ALI) is a severe respiratory disorder occurring in critical care medicine, with high rates of mortality and morbidity. This study aims to screen the potential biomarkers for ALI. Microarray data of lung tissues from lung-specific geranylgeranyl pyrophosphate synthase large subunit 1 knockout and wild-type mice treated with lipopolysaccharide were downloaded. Differentially expressed genes (DEGs) between ALI and wild-type mice were screened. Functional analysis and the protein-protein interaction (PPI) modules were analyzed. Finally, a miRNA-transcription factor (TF)-target regulation network was constructed. Totally, 421 DEGs between ALI and wild-type mice were identified. The upregulated DEGs were mainly enriched in the peroxisome proliferator-activated receptor signaling pathway, and fatty acid metabolic process, while downregulated DEGs were related to cytokine-cytokine receptor interaction and regulation of cytokine production. Cxcl5, Cxcl9, Ccr5, and Cxcr4 were key nodes in the PPI network. In addition, three miRNAs (miR505, miR23A, and miR23B) and three TFs (PU1, CEBPA, and CEBPB) were key molecules in the miRNA-TF-target network. Nine genes including ADRA2A, P2RY12, ADORA1, CXCR1, and CXCR4 were predicted as potential druggable genes. As a conclusion, ADRA2A, P2RY12, ADORA1, CXCL5, CXCL9, CXCR1, and CXCR4 might be novel markers and potential druggable genes in ALI by regulating inflammatory response.