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

Abstract

PDGF-BB (Platelet-derived growth factor BB) and TGF-β1(transforming growth factor β1) 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-β1 on PCNA in VSMCs. The downstream proteins of the TGF-β signalling system in VSMCs, including TGF-β 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-β1 and PCNA, and the increase in PCNA can be partially inhibited by neutralizing anti-TGF-β1 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-β1 antibody. These findings suggest that PDGF-BB promotes PCNA expression in VSMCs partially through TGF-β1 overexpression, and that the TGF-β signalling system involves the molecular mechanism of PDGF-BB in VSMCs.