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 mitogenesis. To that end, investigators have developed cell culture systems adopting tracheal and bronchial myocytes from different species. A growing body of literature suggests that common signal transduction pathways regulate airway smooth muscle cell cycle entry across species lines. This review summarizes what is known about mitogen-activated signal transduction in airway smooth muscle cells. The extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI 3-kinase) pathways appear to be major positive regulators of airway smooth muscle proliferation. It is also conceivable that growth factor stimulation of airway smooth muscle simultaneously elicits signaling through negative regulatory pathways such as the p38 mitogen-activated protein (MAP) kinase pathway, perhaps as a safeguard against excessive growth.
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Department of Pediatrics, University of Chicago Children's Hospital, 5841 S. Maryland Avenue, MC 4064, Chicago, IL 60637-1470, USA.
Hershenson
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MB
D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D008934:Mitogens; D009130:Muscle, Smooth / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000502:physiology
D006133:Growth Substances; D008934:Mitogens; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein