BASIC FIBROBLAST GROWTH-FACTOR INDUCES EXPRESSION OF THE PDGF RECEPTOR-ALPHA ON HUMAN BRONCHIAL SMOOTH-MUSCLE CELLS

Bronchial smooth muscle cell (SMC) hyperplasia is a key feature in the pathology of asthma. Platelet-derived growth factor (PDGF) isoforms a re SMC mitogens. We investigated the effect of basic fibroblast growth factor (bFGF), transforming growth factor-beta 1 (TGF-beta 1), interl eukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) on the PDGF receptor system on human bronchial SMC from three differen t donors. bFGF induced gene expression of the PDGF alpha-receptor (PDG F-R alpha) approximately threefold without altering the PDGF beta-rece ptor (PDGF-R beta). IL-1 beta and TNF-alpha did not affect the PDGF re ceptor system. TGF-beta 1 downregulated PDGF-R alpha mRNA similar to 6 0% without changing PDGF-R beta mRNA levels. Receptor assays showed th at bFGF increased the [I-125]PDGF-AA binding site approximately twofol d, whereas TGF-beta 1 reduced [I-125]PDGF-AA binding similar to 60%. T GF-beta 1, but not latent TGF-beta 1, counteracted the bFGF-induced in crease in [I-125]PDGF-AA binding. PDGF-AA-stimulated tyrosine phosphor ylation on the PDGF-R alpha was enhanced after treatment with bFGF. bF GF pretreatment enhanced the mitogenic response of SMC to PDGF-AA and PDGF-AB. These findings suggest that upregulation of the PDGF-R alpha by bFGF could contribute to SMC hyperplasia during chronic airway infl ammation in asthma.