Synergistic stimulation of airway smooth muscle cell mitogenesis

T. L. Ediger, M. L. Toews

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1076-1082
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume294
Issue number3
StatePublished - Sep 13 2000

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Mitogens
Smooth Muscle Myocytes
GTP-Binding Proteins
Pertussis Toxin
Epidermal Growth Factor
Receptor Protein-Tyrosine Kinases
Protein-Tyrosine Kinases
Mesangial Cells
Platelet-Derived Growth Factor
Carbachol
Transforming Growth Factors
Endothelin-1
Somatomedins
Fibroblast Growth Factor 2
Serum
Vascular Smooth Muscle
Epidermal Growth Factor Receptor
Thrombin
Intercellular Signaling Peptides and Proteins
Fibroblasts

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Synergistic stimulation of airway smooth muscle cell mitogenesis. / Ediger, T. L.; Toews, M. L.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 294, No. 3, 13.09.2000, p. 1076-1082.

Research output: Contribution to journalArticle

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