The contractility and growth of airway smooth muscle play an important role in the pathogenesis of airway hyperresponsiveness and smooth muscle layer thickening, cardinal features of asthma that affects nearly 250-300 million people worldwide. The mechanisms underlying these biological and pathological processes are not fully elucidated. Nestin is a type VI intermediate filament protein that has been implicated in progenitor cell functions and cancer pathogenesis. The functional role of nestin in airway smooth muscle is largely unknown. Pilot studies have shown that nestin may contribute to the regulation of smooth muscle contraction and proliferation. In Aim 1, we will determine the role of nestin in regulating airway smooth muscle contractility and cytoskeletal signaling. In Aim 2, we will assess the role and mechanism of nestin in airway smooth muscle proliferation and the growth factor-mediated pathways. In Aim 3, the potential role of nestin-associated cellular processes in human asthma will be determined. The role of nestin in allergen-induced asthma will also be evaluated in vivo. Completion of these studies should advance our knowledge regarding functional role and mechanism of nestin and cytoskeletal signaling in smooth muscle contractility and growth in vitro, and asthma pathogenesis in vivo. Obtaining this knowledge will facilitate the development of new therapy to treat asthma.

Abnormal contraction and proliferation of airway smooth muscle contributes to the progression of asthma which affects nearly 25-30 million people in the United Sates and 250 million people worldwide. This research project is to explore previously-unknown mechanisms that control airway smooth muscle contraction, proliferation and asthma pathogenesis using sophisticated biotechnology. Obtaining this knowledge is necessary to develop new strategies to treat the disease.