Transcriptional Profiling in Sepsis-induced Experimental Multiple Organ Dysfunction Syndrome. Mus musculus

Sepsis-induced multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in critically ill patients and remains impervious to most therapeutic interventions. We utilized a clinically relevant murine model of MODS induced by ventilator-associated pneumonia to systematically delineate pathways dysregulated in lung, liver, and kidney. We focused on processes commonly activated across injured organs and constructed a MODS-associated network based on connectivity among the gene members of these functionally coherent pathways. Our analyses led to the identification of several putative drivers of MODS whose expression was regulated by epidermal growth factor receptor. Our unbiased, integrative method is a promising approach to unravel mechanisms in system-wide disorders afflicting multiple compartments such as sepsis-induced MODS, and guide the discovery of novel putative therapeutic targets. Overall design: A total of 27 independent microarray experiments were performed in lung, liver and kidneys of mice exposed to a combination of mechanical ventilation and S. aureus pneumonia (MV+SA) or controls. The breakdown is as follows:(1) Lung: MV+SA, N=5; Control, N=4.(2) Liver: MV+SA, N=5; Control, N=3. (3) Kidney: MV+SA, N=5; Control, N=5.