Pan Dabin, Yang Junwei, Lu Fengxiang, Xu Di, Zhou Lei, Shi Aiwu, Cao Kejiang
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, PR, China.
Biochem Cell Biol. 2007 Oct;85(5):606-15. doi: 10.1139/o07-064.
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.
血小板衍生生长因子BB（PDGF - BB）和转化生长因子β1（TGF - β1）是调节血管平滑肌细胞（VSMC）增殖及VSMC中增殖细胞核抗原（PCNA）表达的重要生长因子。PCNA在增殖细胞中高水平表达。本研究旨在评估PDGF - BB诱导的TGF - β1过表达对VSMC中PCNA的影响。同时还研究了VSMC中TGF - β信号系统的下游蛋白，包括TGF - βⅠ型受体（VSMC中的ALK - 5）、Smurf2、Smad2、磷酸化Smad2/3、Smad4和Smad7。我们的结果显示，PDGF - BB显著增加了TGF - β1和PCNA的表达，而PCNA的增加可被中和性抗TGF - β1抗体部分抑制。此外，PDGF - BB增加了ALK - 5、Smurf2、磷酸化Smad2/3和Smad4的表达，但降低了Smad2和Smad7的水平；这些改变可被中和性抗TGF - β1抗体部分恢复。这些发现表明，PDGF - BB部分通过TGF - β1过表达促进VSMC中PCNA的表达，且TGF - β信号系统参与了PDGF - BB在VSMC中的分子机制。
