EGF family ligand-dependent phenotypic modulation of smooth muscle cells through EGF receptor

Biochem Biophys Res Commun. 2001 Feb 23;281(2):373-7. doi: 10.1006/bbrc.2001.4385.

Abstract

The phenotypic modulation of smooth muscle cells (SMCs) is closely associated with the development and progression of various SMC diseases. We investigated the molecular mechanism of phenotypic modulation triggered by EGF family ligands using a primary culture system of differentiated SMCs. Among four EGF-receptor (EGFR) family members, the EGFR was solely activated by EGF, heparin-binding EGF (HB-EGF), transforming growth factor alpha (TGF alpha), epiregulin (ER), and betacellulin (BTC), resulting in induction of phenotypic modulation of SMCs. This effect was mediated through the coordinated activation of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) pathways. These results suggest that EGF family ligand- and EGFR-triggered signaling pathways are critically involved in the phenotypic modulation of SMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Betacellulin
  • Calcium-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / genetics
  • Calponins
  • Cells, Cultured
  • Chick Embryo
  • Enzyme Activation / drug effects
  • Epidermal Growth Factor / pharmacology*
  • Epiregulin
  • ErbB Receptors / drug effects*
  • ErbB Receptors / metabolism
  • Gene Expression Regulation / drug effects
  • Growth Substances / pharmacology
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins*
  • Microfilament Proteins
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth / cytology
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Phenotype
  • Transforming Growth Factor alpha / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Betacellulin
  • Calcium-Binding Proteins
  • Calmodulin-Binding Proteins
  • Epiregulin
  • Growth Substances
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Transforming Growth Factor alpha
  • Epidermal Growth Factor
  • ErbB Receptors
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases