Mitogen-activated signaling in cultured airway smooth muscle cells.
Airway hyperresponsiveness and excess smooth muscle mass coexist in patients with asthma and bronchopulmonary dysplasia. This increase in airway smooth muscle mass, which in part relates to smooth muscle proliferation, may increase bronchoconstrictor-induced airway narrowing, even in the absence of excessive force generation. Thus, there is need for a precise understanding of the events involved in airway smooth muscle mitogenesis. This review examines the inflammatory substances and growth factors that induce airway smooth muscle proliferation, and the signaling pathways that may be involved in the transduction of these extracellular signals to the cell nucleus. Also discussed are various antimitogenic substances and potential mechanisms underlying the inhibition of cell proliferation. Central to the discussion are the extracellular 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 mitogenic stimulation. Insight gained from studies of cultured airway smooth muscle growth and mitogen-activated signaling may shed light on parallel mechanisms that may operate in asthma and in bronchopulmonary dysplasia, and may lead to therapeutic interventions against airway remodeling.
Hershenson
M B
MB
Department of Pediatrics, University of Chicago, IL 60637-1470, USA.
Naureckas
E T
ET
Li
J
J
D000818:Animals; D001249:Asthma / Q000209:etiology / Q000473:pathology; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008934:Mitogens / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
D008934:Mitogens