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 are SMC mitogens. We investigated the effect of basic fibroblast growth factor (bFGF), transforming growth factor-beta 1 (TGF-beta 1), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) on the PDGF receptor system on human bronchial SMC from three different donors. bFGF induced gene expression of the PDGF alpha-receptor (PDGF-R alpha) approximately threefold without altering the PDGF beta-receptor (PDGF-R beta). IL-1 beta and TNF-alpha did not affect the PDGF receptor system. TGF-beta 1 downregulated PDGF-R alpha mRNA approximately 60% without changing PDGF-R beta mRNA levels. Receptor assays showed that bFGF increased the [125I]PDGF-AA binding site approximately twofold, whereas TGF-beta 1 reduced [125I]PDGF-AA binding approximately 60%. TGF-beta 1, but not latent TGF-beta 1, counteracted the bFGF-induced increase in [125I]PDGF-AA binding. PDGF-AA-stimulated tyrosine phosphorylation on the PDGF-R alpha was enhanced after treatment with bFGF, bFGF 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 inflammation in asthma.
Bonner
J C
JC
Airway Inflammation Section, National Institute of Environmental Health Sciences, Research Triangle Park 27709, USA. Bonner_J@NIEHS.NIH.GOV
Badgett
A
A
Lindroos
P M
PM
Coin
P G
PG
D001980:Bronchi / Q000378:metabolism*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor