Lysophosphatidic acid upregulates the epidermal growth factor receptor in human airway smooth muscle cells

Tracy L. Ediger, Bryan L. Danforth, Myron L. Toews

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Human airway smooth muscle cells treated with lysophos-phatidic acid (LPA) and epidermal growth factor (EGF) exhibit synergistic stimulation of mitogenesis (Ediger TL and Toews ML. J Pharmacol Exp Ther 294: 1076-1082, 2000). The effects of LPA treatment of human airway smooth muscle cells on EGF receptor (EGFR) regulation have now been investigated. LPA treatment for 12-24 h resulted in a two-fold increase in 125I-EGF binding and EGFR protein levels as assessed by Western blot analysis. Competition binding as-says indicated single-site binding with an affinity of 3 nM, and the affinity was not changed by LPA treatment. EGFR upregulation was blocked by cycloheximide and actinomycin D, suggesting that LPA influences transcriptional regulation of EGFR expression. Inhibitor studies revealed a prominent role for activation of mitogen-activated protein kinase and p70 ribosomal S6 kinase. Both synergism and EGFR upregulation increased with increased cell density, whereas EGFR expression in control cells decreased. The similar requirements for exposure time, LPA concentrations, and cell confluence suggest that EGFR upregulation may be one contributing factor to the synergistic stimulation of mitogenesis seen with LPA plus EGF.

Original languageEnglish (US)
Pages (from-to)L91-L98
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume282
Issue number1 26-1
DOIs
StatePublished - 2002

Keywords

  • Airway remodeling
  • Epidermal growth factor receptor regulation
  • Proliferation
  • Synergism

ASJC Scopus subject areas

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

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