title: SYSTEM-WIDE MAPPING OF ACTIVATED CIRCUITRY IN EXPERIMENTAL SYSTEMIC INFLAMMATORY RESPONSE SYNDROME.
abstract: 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 systemic inflammatory response syndrome (SIRS) during early MODS induced by ventilator-associated pneumonia to systematically delineate pathways dysregulated in lung, liver, and kidney. We focused on processes commonly activated across at-risk organs and constructed an SIRS-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 early 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 identify putative therapeutic targets.
authors.affiliation: *Computational Medicine Core †Center for Lung Biology ‡Division of Pulmonary and Critical Care Medicine §Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.forename: Daniel
authors.initials: D
authors.lastname: Mar
authors.forename: Karol
authors.initials: K
authors.lastname: Bomsztyk
authors.forename: Oleg
authors.initials: O
authors.lastname: Denisenko
authors.forename: Shireesha
authors.initials: S
authors.lastname: Dhanireddy
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
mesh_terms: D000818:Animals; D051379:Mice; D009102:Multiple Organ Failure / Q000276:immunology* / Q000378:metabolism*; D012121:Respiration, Artificial / Q000009:adverse effects; D018805:Sepsis / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000472:pathogenicity; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000378:metabolism*