Bronchial asthma afflicts more than 5 percent of the U.S. population, and the incidence and prevalence are on the rise. A critical feature of the disease is structural changes in the wall of the airways (airway remodeling), which are correlated with morbidity. There is inadequate information describing the mechanisms of airway remodeling. Several key cells (epithelium, fibroblast, and smooth muscle cell) have been identified as critical players in the remodeling process. However, a study that addresses the interaction amongst these specific cells in response to injuries that mimic an asthmatic exacerbation has not been undertaken. Progress in our understanding is limited by a number of key factors including limited access to remodeled bronchial asthmatic tissue, inherent difficulty in characterizing a chronic response, and differentiating the complex interactions between multiple cells that are present simultaneously in vivo.
The specific aims of the project are to: 1) develop a novel tissue engineered model of the airway wall that consists of epithelial cells, fibroblasts, and smooth muscle cells in the normal anatomic and geometric arrangement, 2) utilize non-invasive optical techniques (two-photon microscopy) to quantify newly synthesized ECM proteins in live tissues, and 3) injure the tissue in a pattern which mimics asthma. Completion of the specific aims will provide answers to key questions related to airway remodeling, and bring us closer to not only halting but also reversing airway remodeling.
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