Mitogen-activated signaling and cell cycle regulation in airway smooth muscle

Increased airway smooth muscle mass has been demonstrated in patients with bronchopulmonary dysplasia and asthma. These data highlight the need for a precise understanding of the events involved in airway smooth muscle mitoge nesis. To that end, investigators have developed cell culture systems adopt ing tracheal and bronchial myocytes from different species. A growing body of literature suggests that common signal transduction pathways regulate ai rway smooth muscle cell cycle entry across species lines. This review summa rizes what is known about mitogen-activated signal transduction in airway s mooth muscle cells. The extracellular signal regulated kinase (ERK) and pho sphatidylinositol 3-kinase (PI 3-kinase) pathways appear to be major positi ve regulators of airway smooth muscle proliferation. It is also conceivable that growth factor stimulation of airway smooth muscle simultaneously elic its signaling through negative regulatory pathways such as the p38 mitogen- activated protein (MAP) kinase pathway, perhaps as a safeguard against exce ssive growth.