Platelet-derived growth factor BB modulates PCNA protein synthesis partially through the transforming growth factor beta signalling pathway in vascular smooth muscle cells

Biochem Cell Biol. 2007 Oct;85(5):606-15. doi: 10.1139/o07-064.

Abstract

PDGF-BB (Platelet-derived growth factor BB) and TGF-beta1(transforming growth factor beta1) are important growth factors in the modulation of vascular smooth muscle cell (VSMC) proliferation and PCNA (proliferating cell nuclear antigen) expression in VSMCs. PCNA expresses at a high level in proliferating cells. The present study aims to assess the effects of PDGF-BB-induced overexpression of TGF-beta1 on PCNA in VSMCs. The downstream proteins of the TGF-beta signalling system in VSMCs, including TGF-beta type I receptor (ALK-5 in VSMCs), Smurf2, Smad2, pSmad2/3, Smad4, and Smad7, were also investigated. Our results revealed that PDGF-BB significantly increased the expressions of TGF-beta1 and PCNA, and the increase in PCNA can be partially inhibited by neutralizing anti-TGF-beta1 antibody. Furthermore, PDGF-BB increased the expression of ALK-5, Smurf2, pSmad2/3, and Smad4, but lowered the levels of Smad2 and Smad7; these alterations were partially restored by neutralizing anti-TGF-beta1 antibody. These findings suggest that PDGF-BB promotes PCNA expression in VSMCs partially through TGF-beta1 overexpression, and that the TGF-beta signalling system involves the molecular mechanism of PDGF-BB in VSMCs.

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Becaplermin
  • Cell Proliferation
  • Dose-Response Relationship, Drug
  • Male
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / metabolism*
  • Platelet-Derived Growth Factor / pharmacology*
  • Proliferating Cell Nuclear Antigen / biosynthesis*
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-sis
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Angiogenesis Inducing Agents
  • Platelet-Derived Growth Factor
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-sis
  • Smad Proteins
  • Transforming Growth Factor beta1
  • Becaplermin