MITOGEN-ACTIVATED SIGNALING IN CULTURED AIRWAY SMOOTH-MUSCLE CELLS

Airway hyperresponsiveness and excess smooth muscle mass coexist in pa tients with asthma and bronchopulmonary dysplasia. This increase in ai rway smooth muscle mass, which in part relates to smooth muscle prolif eration, may increase bronchoconstrictor-induced airway narrowing, eve n in the absence of excessive force generation. Thus, there is need fo r a precise understanding of the events involved in airway smooth musc le mitogenesis. This review examines the inflammatory substances and g rowth factors that induce airway smooth muscle proliferation, and the signaling pathways that may be involved in the transduction of these e xtracellular signals to the cell nucleus. Also discussed are various a ntimitogenic substances and potential mechanisms underlying the inhibi tion of cell proliferation. Central to the discussion are the extracel lular signal regulated kinases (ERKs), serine/threonine kinases of the mitogen-activated protein kinase (MAP kinase) superfamily, which upon activation, translocate from the cytoplasm to the nucleus after mitog enic stimulation. Insight gained from studies of cultured airway smoot h muscle growth and mitogen-activated signaling may shed light on para llel mechanisms that may operate in asthma and in bronchopulmonary dys plasia, and may lead to therapeutic interventions against airway remod eling.