Dominant negative c-Jun inhibits platelet-derived growth factor-directed migration by vascular smooth muscle cells

J Pharmacol Sci. 2003 Feb;91(2):145-8. doi: 10.1254/jphs.91.145.

Abstract

The mitogen-activated protein (MAP) kinase pathways has been shown to be necessary for mitogen-stimulated proliferation, but its role in cell migration has not been fully understood. In this study, we investigated the possible contribution of signaling pathways through c-Jun in platelet-derived growth factor (PDGF)-BB directed cell migration in rat aortic vascular smooth muscle cells (VSMCs) infected with a recombinant adenovirus containing the dominant-negative c-Jun (Ad-DN-c-Jun). DN-c-Jun protein was expressed dose-dependently in VSMCs infected with Ad-DN-c-Jun. Expression of DN-c-Jun significantly inhibited VSMC migration induced by PDGF-BB. Our results provide the first evidence that signaling pathways through c-Jun participates in cell migration induced by PDGF-BB in addition to other MAP kinase pathways in VSMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / drug effects
  • Cell Movement / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Genes, Dominant
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Male
  • Mitogen-Activated Protein Kinase Kinases / physiology
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Platelet-Derived Growth Factor / antagonists & inhibitors*
  • Platelet-Derived Growth Factor / pharmacology*
  • Proto-Oncogene Proteins c-jun / pharmacology*
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-jun
  • Pyridines
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one