Paeoniflorin blocks the proliferation of vascular smooth muscle cells induced by platelet‑derived growth factor‑BB through ROS mediated ERK1/2 and p38 signaling pathways.
Paeoniflorin blocks the proliferation of vascular smooth muscle cells induced by platelet‑derived growth factor‑BB through ROS mediated ERK1/2 and p38 signaling pathways.
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Paeoniflorin通过ROS介导的ERK1/2和P38信号通路阻止了由血小板衍生的生长因子诱导的血管平滑肌细胞的增殖。
DOI：
10.3892/mmr.2017.8093
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发表时间：
2018-01
影响因子：
3.4
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Fan X;Wu J;Yang H;Yan L;Wang S
血管平滑肌细胞（vascular smooth muscle cells，VSMCs）的增殖参与了血管重构的发展。本研究旨在探讨芍药苷（paeoniflorin，PAE）对血小板源性生长因子-BB（plateletderivedgrowthfactor-BB，PDGF-BB）诱导的大鼠血管平滑肌细胞增殖的影响及其分子机制。毒性测定采用Try pan blue exclusion试验。CCK-8法检测细胞增殖，BrdU掺入法检测DNA合成。使用PI染色和荧光激活细胞分选来确定细胞周期进展。使用二氯二氢荧光素二乙酸酯评估细胞内活性氧（ROS）产生的水平。逆转录定量聚合酶链反应测定mRNA表达。Western blot检测p38、JNK、ERK 1/2信号通路的变化。通过划痕试验检测细胞迁移。PAE能显著抑制PDGF-BB诱导的VSMC增殖，且呈剂量和时间依赖性，无细胞毒性。因此，PAE阻断了细胞周期从G 0/G1期到S期的进程。此外，细胞周期的抑制与细胞周期蛋白D1，细胞周期蛋白E，细胞周期蛋白依赖性激酶（CDK）4和CDK 2的RNA表达的抑制以及细胞周期蛋白依赖性激酶抑制剂1A mRNA表达的增加在PDGF-BB刺激的VSMCs。进一步研究表明，PAE对VSMCs增殖的抑制作用与抑制ROS介导的细胞外信号调节激酶（ERK）1/2和p38信号通路有关，而对c-Jun N-末端激酶信号通路无明显影响。这些结果表明，PAE通过ROS介导的ERK 1/2和p38信号通路抑制PDGF-BB诱导的VSMC增殖，提示其可能是血管重塑疾病的可行治疗方法。
The proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. In the present study, the effect of paeoniflorin (PAE) on the platelet derived growth factor-BB (PDGF-BB)-induced proliferation of primary cultured rat VSMCs and its molecular mechanism was investigated. The toxicity was determined by the try pan blue exclusion test. Cell proliferation was determined using a CCK-8 assay, DNA synthesis was assessed by measuring the incorporation of BrdU. Cell cycle progression was determined using PI staining and fluorescence-activated cell sorting. The level of intracellular reactive oxygen species (ROS) generation was assessed using dichlorodihydro fluorescein diacetate. mRNA expression was determined by reverse transcription quantitative polymerase chain reaction. Changes of p38, JNK, ERK1/2 signaling pathways were determined by western blot analysis. Cell migration was detected by scratch assay. PAE was demonstrated to significantly inhibit VSMC proliferation induced by PDGF-BB in a dose-and time-dependent manner without cell cytotoxicity. Thus, PAE blocked progression through the G0/G1 to Sphase of the cell cycle. Furthermore, inhibition of the cell cycle was associated with the inhibition of them RNA expression of cyclin D1, cyclin E, cyclin dependent kinase (CDK) 4 and CDK2 as well as with increased cyclin dependent kinase inhibitor 1A mRNA expression in PDGF-BB-stimulated VSMCs. Further studies showed that the beneficial effect of PAE on blocking VSMCs proliferation was related to the suppression of the ROS-mediated extra cellular signal-regulated kinase (ERK)1/2 and p38 signaling pathways, although PAE had no significant effect on the c-Jun N-terminal kinase signalling pathway. These results demonstrated that PAE suppressed PDGF-BB-induced VSMC proliferation through the ROS-mediated ERK1/2 and p38 signaling pathways, suggesting that it may be a feasible therapy for vascular remodelling diseases.
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