Related Experiment Video
Updated: Mar 30, 2026
Establishment of Central Cord Syndrome Model in C57BL/6J Mouse
Published on: September 8, 2023
SYSTEM-WIDE MAPPING OF ACTIVATED CIRCUITRY IN EXPERIMENTAL SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
Sina A Gharib1, Daniel Mar, Karol Bomsztyk
1*Computational Medicine Core †Center for Lung Biology ‡Division of Pulmonary and Critical Care Medicine §Department of Medicine, University of Washington, Seattle, Washington.
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.
Insights
Sepsis-induced multiple organ dysfunction syndrome (MODS) involves complex pathway dysregulation. This study identified key gene drivers regulated by epidermal growth factor receptor, offering potential therapeutic targets for critical illness.
Area of Science:
- Critical care medicine
- Molecular biology
- Systems biology
Background:
- Sepsis-induced multiple organ dysfunction syndrome (MODS) is a leading cause of death in critically ill patients.
- Effective therapeutic interventions for MODS remain limited.
- Ventilator-associated pneumonia is a common trigger for early MODS.
Purpose of the Study:
- To systematically identify dysregulated molecular pathways in lung, liver, and kidney during early MODS.
- To construct a network of Systemic Inflammatory Response Syndrome (SIRS)-associated genes.
- To identify potential therapeutic targets for sepsis-induced MODS.
Main Methods:
- Utilized a clinically relevant murine model of SIRS and early MODS induced by ventilator-associated pneumonia.
- Focused on commonly activated processes across multiple organs (lung, liver, kidney).
- Constructed an SIRS-associated gene network based on pathway connectivity.
Main Results:
- Identified several key molecular drivers of early MODS.
- Discovered that epidermal growth factor receptor regulates the expression of these identified drivers.
- Revealed common dysregulated pathways across affected organs.
Conclusions:
- An integrative, unbiased network-based approach can unravel mechanisms in system-wide disorders like MODS.
- Epidermal growth factor receptor signaling is implicated in early MODS pathogenesis.
- The identified gene drivers represent potential therapeutic targets for sepsis-induced MODS.
Related Concept Videos
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
01:24Inflammatory Response II: Inflammatory Exudate and Tissue Repair
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the...