Salidroside blocks the proliferation of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB
Salidroside blocks the proliferation of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB
复制标题
DOI：
10.3892/mmr.2014.2238
复制
发表时间：
2014-08-01
影响因子：
3.4
通讯作者：
Wu, Tianyi
中科院分区：
文献类型：
--
作者：
Chen, Changgui;Tang, Yanhong;Wu, Tianyi
肺动脉平滑肌细胞（PASMC）的增殖有助于肺血管重塑的发展，最终导致肺动脉高压。本研究探讨红景天苷对血小板源性生长因子（PDGF）-BB诱导的原代培养大鼠PASMCs增殖的影响及分子机制。所提供的数据表明，红景天苷以剂量和时间依赖性方式显着抑制 PDGF-BB 诱导的 PASMC 的增殖和 DNA 合成，且没有细胞毒性。根据这些发现，红景天苷可阻断细胞周期从 G0/G1 期向 S 期的进展。红景天苷诱导的细胞周期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 2 (CDK2) 和 CDK4 mRNA 表达的抑制以及 PDGF-BB 刺激的 PASMC 中 p27 mRNA 表达的增加有关。进一步的实验表明，红景天苷对阻断PASMCs增殖的有益作用与抑制AKT/糖原合成酶激酶3β（GSK3β）信号通路有关，但不涉及细胞外信号调节激酶1/2、p38和c-Jun-N末端激酶信号通路。这些结果表明，红景天苷通过 AKT/GSK3 β 信号通路抑制 PDGF-BB 诱导的 PASMC 增殖，并表明它可能是治疗肺血管重塑疾病的可行疗法。
The proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the development of pulmonary vascular remodeling, ultimately leading to pulmonary hypertension. In this study, the effects and molecular mechanisms of salidroside on the platelet-derived growth factor (PDGF)-BB-induced proliferation of primary cultured rat PASMCs were investigated. The presented data demonstrated that salidroside significantly inhibited the proliferation and DNA synthesis of PASMCs induced by PDGF-BB in a dose- and time-dependent manner, without cell cytotoxicity. In accordance with these findings, salidroside blocked progression through G0/G1 to S phase of the cell cycle. The salidroside-induced inhibition of the cell cycle was associated with the inhibition of cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2) and CDK4 mRNA expression, as well as an increase in the mRNA expression of p27 in PDGF-BB-stimulated PASMCs. Further experiments showed that the beneficial effect of salidroside on blocking the proliferation of PASMCs was associated with the suppression of the AKT/glycogen synthase kinase 3 beta (GSK3 beta) signaling pathway, but did not involve the extracellular signal-regulated kinase 1/2, p38 and c-Jun-N-terminal kinase signaling pathways. These results indicate that salidroside suppresses PDGF-BB-induced PASMC proliferation through the AKT/GSK3 beta signaling pathway and suggests that it may be a feasible therapy for pulmonary vascular remodeling diseases.