Expression profiling of genes differentially regulated under hyperoxia andmechanical ventilation in mouse model of neonatal chronic lung disease

In order to investigate the pathways underlying oxygen and mechanical ventilation driven pulmonary injury we studied early changes by unbiased transcriptomic analysis. P5-7male C57BL/6J wild type mice (n=3-4/group) were exposed to either room air(control, FiO2=0.21), oxygen (hyperoxia, FiO2=0.4) or mechanical ventilation (180 breaths/min, tracheotomy under sedation) with (MV-O2) and without oxygen rich gas (MV). Lungs were excised after 2 or 8h of treatment, extracted RNA was subjected to whole genome arrays (CodeLink Expression Assay Kit). Differential gene expression as analyzed including function and upstream regulation analysis. Transcriptome analysis reveals 440 significantly regulated genes; 177 genes were regulated with time only (70 upregulated, 107 downregulated), unrelated to any treatment applied. After excluding these genes for further analysis, 2 genes were regulated with hyperoxia exposure (2h: 1 upregulated; 8h: 1 downregulated); 58 genes were regulated with MV showing a differential response related to the duration of ventilation (2h: 4 upregulated, 30 genes downregulated; 8h: 19 upregulated, 5 downregulated). MV-O2 led to the differential regulation of 60 genes (2h: 1 downregulated; 8h: 25 upregulated, 34 downregulated). Transcriptome analysis revealed a differential response of the developing lung to the injury modes of hyperoxia, ventilation, or both. Our results thereby identified putative biomarkers to predict early onset of hyperoxia and ventilation-mediated BPD in preterm infants.