Asthma is a serious lung disease that affects nearly 20 million people in the United Sates and 250 million people worldwide. Airway hyperresponsiveness (AHR) and airway remodeling are cardinal characteristics of asthma. It is known that airway smooth muscle contraction plays a critical role in mediating AHR whereas airway smooth muscle cell proliferation largely contributes to the pathogenesis of airway remodeling. However, the mechanisms that regulate airway smooth muscle contraction and growth are not well understood. Polo-like kinase 1 (Plk1) is a serine/threonine protein kinase that has been implicated mitosis of nonmuscle cells. The functional role of Plk1 in smooth muscle is currently unknown. Our pilot studies have shown that Plk1 is involved in the regulation of airway smooth muscle contraction and cytokinesis, a key step of cell proliferation. The major goal of the project is to unveil the role of Plk1 in airway smooth muscle contraction and cytokinesis in vitro, and the pathogenesis of AHR and airway remodeling in vivo.
In Aims 1 and 2, the role and mechanisms of Plk1 in airway smooth muscle contraction and cytokinesis will be characterized.
In Aim 3, the role of Plk1 in allergen-induced AHR, airway remodeling and airway inflammation will be assessed using animal models of asthma. Completion of these studies should advance our knowledge regarding smooth muscle contraction/cytokinesis and asthma pathology. Obtaining this knowledge may identify Plk1 as a new biological target for the development of new therapy to treat asthma.
Allergic asthma is characterized by airway hyperresponsiveness and airway remodeling, which stems from abnormal airway smooth muscle contraction and proliferation. However, the cellular and molecular mechanisms that regulate smooth muscle contraction and growth are not well elucidated. This project is to reveal previously unknown mechanisms that control airway smooth muscle contraction and proliferation in vitro and asthma pathology in vivo using the state- of-the art technology. Obtaining this knowledge is essential for the development of new strategies to treat the disease.
