Mechanisms of Tissue Remodeling in Sepsis-Induced Acute Lung Injury
Annual rept. 18 Mar 2003-17 Mar 2004
ATLANTA RESEARCH AND EDUCATION FOUNDATION DECATUR GA
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Acute lung injury ALI related to sepsis activates tissue remodeling that is responsible for the excessive deposition and turnover of extracellular matrices. This project will explore the factors that control lung tissue remodeling in the setting of sepsis by focusing on chronic ethanol ingestion, a factor that renders the lung susceptible to ALI. We hypothesize that chronic ethanol ingestion renders the lung susceptible to ALI by acting on alpha-7 nicotinic acetylcholine receptors alpha-7 nAChRs and stimulating the expression of tissue remodeling genes such as that of fibronectin FN. Aberrant deposition of FN affects the structure of the lung and promotes a proinflammatory state that drives the development of ALI after infection. The specific aims are to 1 Determine the role of alpha-7 nAChRs in ethanol induction of FN. 2 Delineate the intracellular pathways responsible for the induction of FN in fibroblasts in response to ethanol. 3 Elucidate the effects of ethanol-induced FN expression on lung cell function. 4 Study ethanol-induced FN expression in a rat model of sepsis-induced ALI. Servicemen and women are exposed to conditions considered risk factors for ALI e.g., trauma, toxic gas, infection. Tissue remodeling is considered key to the development of the irreversible consequences of ALI.
- Anatomy and Physiology
- Medicine and Medical Research