An Inhibitory Effect of Chrysoeriol on Platelet-Derived Growth Factor (PDGF)-Induced Proliferation and PDGF Receptor Signaling in Human Aortic Smooth Muscle Cells

An Inhibitory Effect of Chrysoeriol on Platelet-Derived Growth Factor (PDGF)-Induced Proliferation and PDGF Receptor Signaling in Human Aortic Smooth Muscle Cells
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DOI:
10.1254/jphs.08282fp
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发表时间:
2009-05-01
影响因子:
3.5
通讯作者:
Woo, Je-Tae
Woo, Je-Tae
中科院分区:
医学3区
文献类型:
--
作者:
Cha, Byung-Yoon;Shi, Wen Lei;Woo, Je-Tae

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血小板衍生生长因子(PDGF)-BB 是再狭窄和动脉粥样硬化等各种血管疾病发生和进展中最有效的因素之一。 Chrysoeriol 是一种具有抗氧化和抗炎活性的黄酮类化合物。在这项研究中,我们研究了金油醇对人主动脉平滑肌细胞(HASMC)增殖的影响。 Chrysoeriol 在 5 和 10 muM 浓度下显着抑制 PDGF (20 ng/mL) 诱导的迁移和 [H-3]-胸苷掺入 DNA,且没有任何细胞毒性。 Chrysoeriol 还以浓度依赖性方式阻断 PDGF 刺激的肌动蛋白丝解离并抑制 PDGF β 受体 (R β) 磷酸化。结果,PDGF-R beta 的下游信号转导途径,包括 EPK1/2、p38 和 Akt 磷酸化,也以相同的模式被金油醇抑制。这些研究结果表明,除了其抗氧化和抗炎活性外,金油醇还可用于预防和治疗血管疾病以及冠状动脉血管成形术后的再狭窄。
Platelet-derived growth factor (PDGF)-BB is one of the most potent factors in the development and progression of various vascular disorders such as restenosis and atherosclerosis. Chrysoeriol is a flavonoid with antioxidant and anti-inflammatory activities. In this study, we investigated the effect of chrysoeriol on the proliferation of human aortic smooth muscle cells (HASMC). Chrysoeriol significantly inhibited PDGF (20 ng/mL)-induced migration and [H-3]-thymidine incorporation into DNA at concentrations of 5 and 10 mu M Without any cytotoxicity. Chrysoeriol also blocked PDGF-stimulated dissociation of actin filament and inhibited PDGF beta-receptor (R beta) phosphorylation in a concentration-dependent manner. As a result, the down-stream signal transduction pathways of PDGF-R beta including EPK1/2, p38, and Akt phosphorylation, were also inhibited by chrysoeriol in the same pattern. These findings Suggest that in addition to its antioxidant and anti-inflammatory activities, chrysoeriol may be used for the prevention and treatment of vascular diseases and during restenosis after coronary angioplasty.