Transforming growth factor-beta1 in asthmatic airway smooth muscle enlargement: is fibroblast growth factor-2 required?
Enlargement of airway smooth muscle (ASM) tissue around the bronchi/bronchioles is a histopathological signature of asthmatic airway remodelling and has been suggested to play a critical role in the increased lung resistance and airway hyperresponsiveness seen in asthmatic patients. The pleiotropic cytokine, TGF-beta1, is believed to contribute to several aspects of asthmatic airway remodelling and is known to influence the growth of many cell types. Increased TGF-beta1 expression/signalling and ASM growth have been shown to occur concurrently in animal models of asthma. Abundant studies further substantiate this association by showing that therapeutic strategies that reduce or prevent TGF-beta1 overexpression/signalling lead to a parallel decrease or prevention of ASM enlargement. Finally, recent findings have supported a direct link of causality between TGF-beta1 overexpression/signalling and the overgrowth of ASM tissue. To follow-up on these in vivo studies, many investigators have pursued detailed investigation of ASM in cell culture conditions, assessing the direct role of TGF-beta1 on cellular proliferation and/or hypertrophy. Inconsistencies among the in vitro studies suggest that the effect of TGF-beta1 on ASM cell proliferation/hypertrophy is contextual. A hypothesis focusing on fibroblast growth factor-2 is presented at the end of this review, which could potentially reconcile the apparent discrepancy between the conflicting in vitro findings with the consistent in vivo finding that TGF-beta1 is required for ASM enlargement in asthma.
Bossé
Y
Y
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Medicine, Respiratory Division, University of British Columbia, Vancouver, BC, Canada. ybosse@mrl.ubc.ca
Stankova
J
J
Rola-Pleszczynski
M
M
D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2