The role of sFRP-1 and Wnt as development and repair genes on airway remodeling processes in a mouse model of asthma

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Asthma is currently the most common chronic disease among children, although the underlying environmental, immunological and genetic principles are still the focus of ongoing research. The interaction between genetic and environmental factors, which results in a pathological airway obstruction and structural changes known as airway remodeling is the widely accepted basic principle in the development of asthma. Lung development research is not only important from an embryologic point of view, but repair processes often resemble developmental processes and therefore call for a combined research endeavor. Lung development and repair genes are not only known to play a physiological role in restructuring processes after lung injury but have also been associated with the development of diseases. The present project proposal focuses on the relationship between asthma, airway remodeling and lung developmental and repair genes. The main aim is to examine an important group of these genes, the Wnt signaling pathway and its modulating sFRP-1 through knock-out mice in development and in an asthma model. Preliminary data shows an up regulation of one important Wnt pathway for asthma in sFRP-1 knock-out mice and in proliferating bronchial smooth muscle cells. Therefore, well-described sFRP-1-knock-out mice will be exposed to a chronic asthma model and invasive lung function parameters, histological structure and expression patterns will be examined. To extend this project to underlying mechanistical questions involved in the Wnt signaling pathway, its interactions and role in development, Wnt10b-knock-out mice will be examined. Wnt10b has been postulated as a ligand for sFRP-1 and is therefore of special interest. Their lung phenotype will be characterized through histological studies, expression patterns and localization studies.