Asthma has become an epidemic affecting more than 155 million people in the world. Asthma is chronic disease characterized by exacerbations and progressive loss of lung function. Despite our understanding of asthma as an inflammatory disease and knowledge describing mechanisms by which inflammation is initiated, there is little information on mechanisms related to resolution of inflammation or on the impact on lung function and structural changes. Our lab has data supporting the role of several components of the Extracellular Matrix (ECM) in the development and pathogenesis of asthma. Our lab is focusing on the investigation of mechanisms by which the extracellular matrix proteins, Tumor necrosis factor stimulated gene 6 (TSG-6) and Inter-alpha-trypsin inhibitor (IaI), participate in the development of asthma in vivo and their role in the organization of the hyaluronan matrix, in the recruitment of inflammatory cells within the matrix, and in maintaining the structural integrity of the lung. These studies will help to determine the distribution and changes in matrix composition in the airway and if these changes are permanent or resolve after antigen withdrawal and resolution of inflammation, as well as providing insight into the mechanisms by which hyaluronan is synthesized and degraded in the airway. Our long-term goal is to define mechanisms that regulate the synthesis, degradation and organization of hyaluronan, TSG-6 and IaI within the lung, how these matrix components affect inflammation and their effects on lung structure and function.
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