[Platelet-derived growth factor-BB inhibited p21(WAF1) expression partially through transforming growth factor-beta signalling system in vascular smooth muscle cell].
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.
Pan
Da-Bin
DB
Department of Cardiology, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu 241001, China.
Ke
Yong-Sheng
YS
Liu
Wen-Jie
WJ
Wei
You-Quan
YQ
Tang
Jun
J
Cao
Heng
H
D000818:Animals; D000077214:Becaplermin; D002455:Cell Division; D002477:Cells; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin