Platelet-derived growth factor-BB inhibited p21(WAF1) expression partially through transforming growth factor-beta signalling system in vascular smooth muscle cell.
- Author:
Da-Bin PAN
1
;
Yong-Sheng KE
;
Wen-Jie LIU
;
You-Quan WEI
;
Jun TANG
;
Heng CAO
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Division; Cells; Cyclin-Dependent Kinase Inhibitor p21; metabolism; Male; Muscle, Smooth, Vascular; cytology; metabolism; Myocytes, Smooth Muscle; drug effects; metabolism; Platelet-Derived Growth Factor; pharmacology; Proto-Oncogene Proteins c-sis; Rats; Rats, Sprague-Dawley; Signal Transduction; drug effects; Transforming Growth Factor beta1; metabolism
- From: Chinese Journal of Cardiology 2010;38(2):160-165
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSTGF-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.
RESULTSPDGF-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.
CONCLUSIONSThese 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.
