Platelet-derived growth factor BB modulates PCNA protein synthesis partially through the transforming growth factor beta signalling pathway in vascular smooth muscle cells.
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.
Pan
Dabin
D
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, PR, China.
Yang
Junwei
J
Lu
Fengxiang
F
Xu
Di
D
Zhou
Lei
L
Shi
Aiwu
A
Cao
Kejiang
K
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin