Mechanisms of Tissue Remodeling in Sepsis-Induced Acute Lung Injury
Abstract
Acute lung injury (ALl) activates tissue remodeling that is responsible for the excessive deposition and turnover of extracellular matrices. This project will explore the factors that control tissue remodeling in this setting by focusing on chronic ethanol ingestion, a factor that renders the lung susceptible to ALl. We hypothesize that chronic ethanol ingestion renders the lung susceptible to ALl by acting on a7 nicotinic acetylcholine receptors (a7 nACliRs) and stimulating the expression of tissue remodeling genes such as fibronectin (FN). Aberrant deposition of FN affects the structure of the lung and promotes a "proinfiammatory state" that drives the development of ALl after infection. The specific aims are to: 1) Determine the role of a7 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 ALl. Service men and women are exposed to conditions considered risk factors for ALl (e.g., trauma, toxic gas, infection). Tissue remodeling is considered key to the development of the irreversible consequences of ALl.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA421699
Entities
People
- David M. Guidot
- Jesse Roman