Li Li, Li Wei, Ren Zhong, He ShuYing, Xu GuangLin, Yang LiNa
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Vasc Endovascular Surg. 2012 Jul;46(5):393-400. doi: 10.1177/1538574412442595. Epub 2012 May 17.
In this study, the effect of heparin-derived oligosaccharide on bovine vascular smooth muscle cell (VSMC) proliferation and signal transduction mechanism was investigated. Extracellular-signal-regulated kinase (ERK) 1/2 has been implicated in the regulation of various cellular functions including proliferation, and we sought to define a functional role for ERK 1/2 in an established proliferation model in order to find a possible mechanism for inhibition of VSMC proliferation by heparin-derived oligosaccharide. The VSMC proliferation model was developed by platelet-derived growth factor (PDGF), and the level of ERK 1/2 protein and messenger RNA was determined by reverse transcriptase-polymerase chain reaction, Western blotting, and immunocytochemical methods. Flow cytometry analysis indicated that heparin-derived oligosaccharide blocked PDGF-induced cell cycle progression by arresting cells in the G0/G1 phase. The results imply that heparin-derived oligosaccharide inhibits VSMC proliferation by moderating the gene and the phosphorylation levels of ERK 1/2, eventually blocking G1/S transition, may be one of the mechanisms for inhibition of VSMC proliferation by heparin-derived oligosaccharide.
本研究探讨了肝素衍生寡糖对牛血管平滑肌细胞(VSMC)增殖及信号转导机制的影响。细胞外信号调节激酶(ERK)1/2参与包括增殖在内的多种细胞功能的调节,我们试图在已建立的增殖模型中确定ERK 1/2的功能作用,以便找到肝素衍生寡糖抑制VSMC增殖的可能机制。VSMC增殖模型由血小板衍生生长因子(PDGF)构建,通过逆转录-聚合酶链反应、蛋白质印迹法和免疫细胞化学方法测定ERK 1/2蛋白和信使RNA的水平。流式细胞术分析表明,肝素衍生寡糖通过使细胞停滞在G0/G1期来阻断PDGF诱导的细胞周期进程。结果表明,肝素衍生寡糖可能通过调节ERK 1/2的基因和磷酸化水平来抑制VSMC增殖,最终阻断G1/S期转换,这可能是肝素衍生寡糖抑制VSMC增殖的机制之一。