Effects of Growth Factors and Extracellular Matrix on Survival of Human Airway Smooth Muscle Cells

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Abstract
Airway remodeling complicates longstanding asthma. It is characterized by an increase in the number of airway smooth muscle cells (SMCs) as well as an increase in and alteration of the type of extra-cellular matrix (ECM) in the airways. Although the number of SMCs in the airways depends on the balance of cell proliferation and cell death, studies to date have concentrated on factors affecting SMC proliferation. Here we report the first study on airway SMC survival factors: these cells receive a strong survival signal, which is not dependent on the known growth factor mitogens. We identified the ECM factors fibronectin, laminin, and collagens I and IV as important anti-apoptotic elements, and characterized the expression of the ECM receptors (integrins) on cultured SMC. Functionally blocking antibody and peptide studies revealed the alpha(5)beta(1) integrin to be an important transducer of the ECM-derived survival signal in these cells. Confocal microscopy confirmed the striking effects that discrete ECM factors have on SMC phenotype, notably the cytoskeleton. In summary, our data improves the understanding of the mechanisms underlying airway remodeling by outlining the key survival factors for airway SMC and by highlighting the impact of the cell-matrix interactions on cell death and phenotype.