Transforming growth factor β1 increases fibronectin deposition through integrin receptor α5 β1 on human airway smooth muscle

• Published in: Journal of allergy and clinical immunology 2008, Vol.121 (4), p.1034-1039.e4
• Main Authors: Moir, Lyn M., PhD, Burgess, Janette K., PhD, Black, Judith L., MBBS, PhD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2007.12.1159

Background Integrin receptors signal to and from the extracellular matrix. Altered expression of the integrin receptors, such as the fibronectin receptor α5 β1 , might be implicated in extracellular matrix accumulation in airway remodeling in asthma. Objective We examined the effect of TGF-β stimulation on integrin α5 β1 expression and the role of α5 β1 in fibronectin deposition and proliferation. Methods Integrin subunit α5 and β1 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 α5 β1 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 α5 and β1 subunits. The effect of blocking α5 β1 receptor on fibronectin deposition was assessed by means of immunocytochemistry. Results Proliferation of ASM cells from asthmatic and nonasthmatic subjects was inhibited by blocking the fibronectin receptor subunit α5 β1 . TGF-β–induced α5 β1 was extracellular signal-regulated kinase dependent but not phosphoinositide-3 kinase or p38 dependent. Blockade of the α5 β1 receptor inhibited TGF-β–induced fibronectin matrix deposition. Conclusion Through its increased expression by the profibrotic stimulus TGF-β, integrin α5 β1 might be important in regulating fibronectin deposition.