Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling
Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle cells via JNK1/2-dependent signaling
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DOI：
10.1038/aps.2011.105
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发表时间：
2011-11-01
影响因子：
8.2
通讯作者：
Hsieh, Cheng-Ying
中科院分区：
文献类型：
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作者：
Chang, Yi;Uen, Yih-Huei;Hsieh, Cheng-Ying
目的：观察免疫调节剂铂对大鼠血管平滑肌细胞(VSMCs)增殖的抑制作用。用四甲基偶氮唑盐比色法检测细胞增殖情况。用流式细胞仪分析细胞周期。免疫印迹法检测c-jun氨基末端激酶1/2、细胞外信号调节激酶1/2、AKT和c-jun磷酸化或p27的表达。结果：铂(1-5mU/L)可显著抑制血小板衍生生长因子BB(10 ng/mL)或10%胎牛血清刺激的VSMC增殖，并使细胞周期停滞于S和G(2)/M期。相同浓度的铂可显著抑制PDGF-BB刺激的VSMCs中JNK1/2的磷酸化，但不抑制ERK1/2或AKT的磷酸化。结论：铂可能通过抑制c-jun和c-jun的磷酸化，逆转p27的下调，使细胞周期停滞于S和G(2)/M期，从而抑制VSMC的增殖。因此，铂素可能是一种降低VSMC异常增殖和相关血管疾病风险的新方法。
Aim: To examine the inhibitory actions of the immunoregulator platonin against proliferation of rat vascular smooth muscle cells (VSMCs).Methods: VSMCs were prepared from the thoracic aortas of male Wistar rats. Cell proliferation was examined using MTT assays. Cell cycles were analyzed using flow cytometry. c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, AKT, and c-Jun phosphorylation or p27 expression were detected using immunoblotting.Results: Pretreatment with platonin (1-5 mu mol/L) significantly suppressed VSMC proliferation stimulated by PDGF-BB (10 ng/mL) or 10% fetal bovine serum (FBS), and arrested cell cycle progression in the S and G(2)/M phases. The same concentrations of platonin significantly inhibited the phosphorylation of JNK1/2 but not ERK1/2 or AKT in VSMCs stimulated by PDGF-BB. Furthermore, platonin also attenuated c-Jun phosphorylation and markedly reversed the down-regulation of p27 expression after PDGF-BB stimulation.Conclusion: Platonin inhibited VSMC proliferation, possibly via inhibiting phosphorylation of JNK1/2 and c-Jun, and reversal of p27 down-regulation, thereby leading to cell cycle arrest at the S and G(2)/M phases. Thus, platonin may represent a novel approach for lowering the risk of abnormal VSMC proliferation and related vascular diseases.