Impact of extracellular matrix and strain on proliferation of bovine airway smooth muscle.

Abstract

1. The proliferation of airway smooth muscle (ASM) and collagen deposition are major contributors to airway remodelling in asthma that may be an important component of airway hyperresponsiveness. The ratio of collagen to laminin in asthma is increased as a result of fibrosis. 2. We investigated the effects of the extracellular matrix proteins laminin and collagen type I, as well as airway cell elongation (mechanical strain), on the proliferative responses of cultured bovine ASM cells and the impact of these biomechanical influences on glucocorticoid antimitogenic actions. 3. Bovine ASM cells were cultured onto a flexible silastic membrane coated with laminin or collagen. Cells were pretreated with dexamethasone (100 nmol/L) prior to incubation with the mitogen basic fibroblast growth factor (bFGF) for 72 h, at which time cells were enumerated. Cells were either subjected to mechanical strain (cell elongation) by stretching the flexible silastic membrane or were grown under static conditions. 4. Culture on collagen without elongation enhanced ASM proliferation compared with cells grown on laminin. Cells grown on laminin and subjected to 4% elongation did not respond to the mitogenic actions of bFGF. 5. Dexamethasone-mediated inhibition of bFGF-induced proliferation was unaffected by the extracellular matrix on which cells were seeded, or the degree of cell elongation. 6. These data support the hypothesis that the asthmatic airway wall microenvironment (collagen, reduced airway strain) enhances the proliferation of ASM cells.