Airway smooth muscle: A modulator of airway remodeling in asthma

Asthma is a disease characterized, in part, by airway hyperresponsiveness and inflammation. Although asthma typically induces reversible airway obstruction, in some patients with asthma, airflow obstruction can become irreversible. Such obstruction might be a consequence of persistent structural changes in the airway wall caused by the frequent stimulation of airway smooth muscle (ASM) by contractile agonists, inflammatory mediators, and growth factors. Traditional concepts concerning airway inflammation have focused on trafficking leukocytes and on the effects of inflammatory mediators, cytokines, and chemokines secreted by these cells. Recent studies suggest that ASM cells might modulate airway remodeling by secreting cytokines, growth factors, or matrix proteins and by expressing cell adhesion molecules and other potential costimulatory molecules. These ASM cell functions might directly or indirectly modulate submucosal airway inflammation and promote airway remodeling.

Key words: Asthma, signal transduction, smooth muscle, proliferation, synthetic function

Abbreviations used: ADAM, A disintegrinase and metalloproteinase, ASM, Airway smooth muscle, ECM, Extracellular matrix, ERK, Extracellular signal-regulated kinase, GPCR, G protein–coupled receptor, LTD₄, Leukotriene D₄, MCP, Monocyte chemotactic protein, MMP, Matrix metalloproteinase, PDGF, Platelet-derived growth factor, PI3K, Phosphatidylinositol 3-kinase, RTK, Receptor tyrosine kinase, STAT, Signal transducer and activator of transcription, VEGF, Vascular endothelial growth factor