[Platelet-derived growth factor-BB inhibited p21(WAF1) expression partially through transforming growth factor-beta signalling system in vascular smooth muscle cell]

Abstract

Objective: To assess if the modulating effect of platelet-derived growth factor (PDGF)-BB on p21(WAF1) was mediated by upregulating transforming growth factor (TGF)-beta(1) expression in vascular smooth muscle cells (VSMC).

Methods: TGF-beta(1) mRNA and protein expressions were measured by reverse transcription-PCR and ELISA, the protein expressions of p21(WAF1) and the downstream TGF-beta signalling including TGF-beta type I receptor (ALK-5 in VSMC), Smurf2, pSmad2/3, Smad4, Smad7 were detected by Western blot.

Results: PDGF-BB significantly upregulated the expressions of TGF-beta(1) at mRNA (0.79-fold) and protein (1.98-fold) levels in VSMC, significantly inhibited the expression of p21(WAF1) (-67 +/- 12)%, and enhanced the expressions of ALK-5, pSmad2/3, Smad4, Smurf2 protein by 1.21-fold, 0.95-fold, 0.69-fold and 2.55-fold respectively, inhibited Smad7 expression (-65 +/- 9)%, these alterations were partially restored by anti-TGF-beta(1) neutralizing antibody.

Conclusions: These findings suggested that PDGF-BB inhibited p21(WAF1) expression in VSMC partially through upregulating TGF-beta(1) expression via PDGF-BB and TGF-beta signalling pathways.