Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells

D. Roselyn Cerutis, Makoto Nogami, Jodi L. Anderson, James D. Churchill, Debra Romberger, Stephen I. Rennard, Myron Lee Toews

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Enhanced proliferation of airway smooth muscle is thought to contribute to the pathogenesis of asthma and other obstructive airway diseases. Lysophosphatidic acid (LPA) is a simple bioactive lipid mediator that stimulates mitogenesis in fibroblasts and some other cell types. The effects of LPA on mitogenesis of cultured human airway smooth muscle cells were determined by measuring [ 3 H]thymidine incorporation into cellular DNA. LPA induced a concentration-dependent stimulation of [ 3 H]thymidine incorporation of a similar magnitude to that induced by serum, with the effects of 50 μM LPA being similar to those of 5% serum. Stimulation by LPA and by serum was almost completely eliminated in cells exposed to pertussis toxin, indicating involvement of a pertussis toxin-sensitive G protein in mitogenic signaling by these agents. Epidermal growth factor (EGF) induced stimulation of a similar magnitude as that with LPA, but the stimulation by EGF was insensitive to pertussis toxin. LPA and EGF, when added together, exhibited a markedly synergistic stimulation of [ 3 H]thymidine incorporation that was typically 10-fold greater than the stimulation with either agent alone. LPA and EGF also stimulated mitogenesis assessed by cell growth, and again LPA and EGF together exhibited synergism. These results suggest the possibility that stimulation of airway smooth muscle cell proliferation by LPA, either alone or by enhancing effects of other growth factors, could play a role in normal airway remodeling or in the pathological proliferation of smooth muscle in various airway diseases.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume273
Issue number1 17-1
StatePublished - Jul 1 1997

Fingerprint

Epidermal Growth Factor
Smooth Muscle Myocytes
Pertussis Toxin
Thymidine
Smooth Muscle
Serum
lysophosphatidic acid
Airway Remodeling
GTP-Binding Proteins
Intercellular Signaling Peptides and Proteins
Asthma
Fibroblasts
Cell Proliferation
Lipids
DNA
Growth

Keywords

  • Deoxyribonucleic acid synthesis
  • Epidermal growth factor
  • G proteins
  • Lipid mediators
  • Proliferation
  • Synergism

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells. / Cerutis, D. Roselyn; Nogami, Makoto; Anderson, Jodi L.; Churchill, James D.; Romberger, Debra; Rennard, Stephen I.; Toews, Myron Lee.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 273, No. 1 17-1, 01.07.1997.

Research output: Contribution to journalArticle

Cerutis, D. Roselyn ; Nogami, Makoto ; Anderson, Jodi L. ; Churchill, James D. ; Romberger, Debra ; Rennard, Stephen I. ; Toews, Myron Lee. / Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1997 ; Vol. 273, No. 1 17-1.
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