Synergistic Stimulation of Airway Smooth Muscle Cell Mitogenesis

Previous studies showed that human airway smooth muscle (HASM) cells treated with lysophosphatidic acid (LPA), a pertussis toxin (PTX)-sensitive G protein-coupled (GPC) mitogen, simultaneously with epidermal growth factor (EGF), a receptor tyrosine kinase (RTK) mitogen, exhibit markedly synergistic...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2000-09, Vol.294 (3), p.1076
Main Authors: Ediger, T L, Toews, M L
Format: Article
Language:English
Subjects:
Cell Division
Cells, Cultured
DNA - biosynthesis
Drug Synergism
Epidermal Growth Factor - pharmacology
Fibroblasts - cytology
Glomerular Mesangium - cytology
Growth Substances - pharmacology
Growth Substances - physiology
GTP-Binding Proteins - metabolism
Humans
Lung - cytology
Lysophospholipids - pharmacology
Mitogens - pharmacology
Muscle, Smooth - cytology
Muscle, Smooth, Vascular - cytology
Receptor Protein-Tyrosine Kinases - pharmacology
S Phase
Skin - cytology
Trachea - cytology
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Summary:Previous studies showed that human airway smooth muscle (HASM) cells treated with lysophosphatidic acid (LPA), a pertussis toxin (PTX)-sensitive G protein-coupled (GPC) mitogen, simultaneously with epidermal growth factor (EGF), a receptor tyrosine kinase (RTK) mitogen, exhibit markedly synergistic stimulation of mitogenesis. We now show that the RTK mitogens basic fibroblast growth factor, insulin-like growth factor-1, insulin, platelet-derived growth factor-AA, and platelet-derived growth factor-BB, as well as transforming growth factor-β, all induced synergistic stimulation of mitogenesis in the presence of LPA. The PTX-sensitive GPC mitogens carbachol and endothelin-1 and the PTX-insensitive GPC mitogens sphingosine-1-phosphate and thrombin exhibited synergistic stimulation together with EGF. Several RTK-RTK growth factor pairs and GPC-GPC mitogen pairs were also synergistic. HASM cells showed synergistic responses to serum plus EGF but not to serum plus LPA. Testing various other cell types showed that synergism between LPA and EGF occurred in other smooth muscle cells because both vascular smooth muscle cells and mesangial cells exhibited synergism. Additionally, human fetal lung fibroblasts also showed striking synergism. These results indicate that HASM cells can respond synergistically to a wide variety of mitogen combinations and that this synergism is a feature shared with other contractile cell types.
ISSN:0022-3565
1521-0103