Integrin receptors signal to and from the extracellular matrix. Altered expression of the integrin receptors, such as the fibronectin receptor α 5 β 1 , might be implicated in extracellular matrix accumulation in airway remodeling in asthma.We examined the effect of TGF-β stimulation on integrin α 5 β 1 expression and the role of α 5 β 1 in fibronectin deposition and proliferation.Integrin subunit α 5 and β 1 expression in airway smooth muscle (ASM) from subjects with and without asthma was examined by means of PCR and flow cytometry. The effect of blocking α 5 β 1 receptor on ASM proliferation to FBS was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay. Cells were stimulated with TGF-β in the presence or absence of extracellular signal-regulated kinase, phosphoinositide-3 kinase, or p38 inhibitors and antibodies to the α 5 and β 1 subunits. The effect of blocking α 5 β 1 receptor on fibronectin deposition was assessed by means of immunocytochemistry.Proliferation of ASM cells from asthmatic and nonasthmatic subjects was inhibited by blocking the fibronectin receptor subunit α 5 β 1 . TGF-β–induced α 5 β 1 was extracellular signal-regulated kinase dependent but not phosphoinositide-3 kinase or p38 dependent. Blockade of the α 5 β 1 receptor inhibited TGF-β–induced fibronectin matrix deposition.Through its increased expression by the profibrotic stimulus TGF-β, integrin α 5 β 1 might be important in regulating fibronectin deposition.