Mechanical and epithelial cell regulation of airway smooth muscle contractile function

It is the airway smooth muscle that surrounds the airways in the lung that ultimately causes constriction leading to difficulty breathing in asthma. Asthma alters the airways in ways that can grow more smooth muscle and make the muscle contract more. These changes include changes in the tissue that surrounds the smooth muscle, changes that increase the constant, baseline contraction of the muscle, as well as changes in the airway epithelial cells that line the inside surfaces of the airways. We think that some or all of these changes can lead to changes in the proteins inside smooth muscle cells that can cause more smooth muscle to grow or to become more contractile. Both of these changes can lead to worsening of airway function in asthma, leading to more narrowed airways during an asthma attack. We will do experiments to examine these effects, using airway smooth muscle and airway epithelial cells, grown on special surfaces and in special gels. We will measure the changes in the growth of airway smooth muscle and changes in the ability of the airway smooth muscle to contract, as well as changes in the structure of the cells. In this way we will determine which of these changes outside the smooth muscle, are more important to changing how smooth muscle contracts, and which are most important for worsening airway constriction. This will help us decide how best in future to develop methods to stop these changes in the airway smooth muscle, and improve the health and quality of life of patients that suffer from asthma.