In vitro wounding of airway smooth muscle cell monolayers increases expression of TGF-beta receptors.
During an exacerbation of asthma, there is bronchial epithelial cell injury and influx of inflammatory cells. In these instances, the release of proteases and various cytokines could lead to injury of the airway smooth muscle cells (ASMCs). Airway remodeling is a characteristic finding in asthma but the role of ASMC injury in remodeling is unknown. Previously, we demonstrated that mechanical wounding of confluent monolayers of bovine ASMCs resulted in the release of biologically active transforming growth factor-beta1 (TGF-beta1), which in turn, induced collagen I expression. In the present study, we demonstrate that after mechanical wounding, ASMCs had an increased expression of the signal transducing TGF-beta receptors TbetaR-I and TbetaR-II as detected by flow cytometry and Western analysis. Corticosteroids are standard therapy in asthma and the presence of dexamethasone decreased wound-induced release of TGF-beta1 and the expression of collagen I, fibronectin, and TbetaR-II. These results suggest that ASMC injury may play an important role in airway fibrosis mediated by TGF-beta1, which can be prevented by the use of corticosteroids.
Division of Respiratory Medicine, Department of Medicine, Vancouver Hospital and Health Sciences Centre, The University of British Columbia, 655 West 12th Avenue, Vancouver, BC, Canada V5Z 4R4.
Gang
G
Chen
Nasreen
N
Khalil
D030201:Activin Receptors, Type I / Q000096:biosynthesis; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005353:Fibronectins / Q000096:biosynthesis; D005434:Flow Cytometry; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D013314:Stress, Mechanical; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000893:Anti-Inflammatory Agents; D005353:Fibronectins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003907:Dexamethasone; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II