| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6260
Human airway smooth muscle cells treated with lysophosphatidic 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 twofold increase in 125I-EGF binding and EGFR protein levels as assessed by Western blot analysis. Competition binding assays 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.
epidermal growth factor receptor regulation; airway remodeling; proliferation; synergism
This article has been cited by other articles:
|
|
 |
|
  D. He, Y. Su, P. V. Usatyuk, E. Wm. Spannhake, P. Kogut, J. Solway, V. Natarajan, and Y. Zhao Lysophosphatidic Acid Enhances Pulmonary Epithelial Barrier Integrity and Protects Endotoxin-induced Epithelial Barrier Disruption and Lung Injury J. Biol. Chem., September 4, 2009; 284(36): 24123 - 24132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Kassel, N. A. Schulte, and M. L. Toews Modulation of epidermal growth factor receptor binding to human airway smooth muscle cells by glucocorticoids and {beta}2-adrenergic receptor agonists Am J Physiol Lung Cell Mol Physiol, April 1, 2009; 296(4): L693 - L699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Kassel, P. R. Dodmane, N. A. Schulte, and M. L. Toews Lysophosphatidic Acid Induces Rapid and Sustained Decreases in Epidermal Growth Factor Receptor Binding via Different Signaling Pathways in BEAS-2B Airway Epithelial Cells J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 809 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Kassel, N. A. Schulte, S. M. Parker, A. D. Lanik, and M. L. Toews Lysophosphatidic Acid Decreases Epidermal Growth Factor Receptor Binding in Airway Epithelial Cells J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 109 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rubenfeld, J. Guo, N. Sookrung, R. Chen, W. Chaicumpa, V. Casolaro, Y. Zhao, V. Natarajan, and S. Georas Lysophosphatidic acid enhances interleukin-13 gene expression and promoter activity in T cells Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L66 - L74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Sutcliffe and A J Knox Muscling into cystic fibrosis airways Thorax, March 1, 2005; 60(3): 181 - 182. [Full Text] [PDF]
|
|
|
|
|
|
B. B. Vargaftig and M. Singer Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L808 - L818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.L. Ediger, N.A. Schulte, T.J. Murphy, and M.L. Toews Transcription factor activation and mitogenic synergism in airway smooth muscle cells Eur. Respir. J., May 1, 2003; 21(5): 759 - 769. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
