Paeonol regulates hypoxia-induced proliferation of pulmonary artery smooth muscle cells via EKR 1/2 signalling
Paeonol regulates hypoxia-induced proliferation of pulmonary artery smooth muscle cells via EKR 1/2 signalling
复制标题
丹皮酚通过 EKR 1/2 信号调节缺氧诱导的肺动脉平滑肌细胞增殖
DOI：
10.1016/j.ejphar.2018.07.017
复制
发表时间：
2018-09-05
影响因子：
5
通讯作者：
Zhu, Daling
中科院分区：
文献类型：
--
作者：
Zhang, Lixin;Ma, Cui;Zhu, Daling
肺动脉高压（PH）是一种发育性疾病，其特征是阻塞性血管重塑，部分原因是肺动脉平滑肌细胞（PASMCs）过度增殖。丹皮酚对血管细胞增殖、迁移和炎症有重要作用，但研究人员尚未确定丹皮酚是否参与肺血管重塑的发展和进展。我们探讨了丹皮酚对缺氧PASMCs的显着抗增殖作用，这被认为是由细胞外信号调节激酶1和2（ERK 1/2）信号通路介导的。在这项研究中，缺氧啮齿动物PH模型，蛋白质印迹，流式细胞术，免疫化学和肺血管和右心室（RV）血管的形态计量学分析进行。炔雌醇逆转缺氧诱导的右心室功能、右心室收缩压和中壁增厚的增加。同时，丹皮酚可改善缺氧诱导的PASMCs增殖。丹皮酚还以ERK 1/2依赖的方式调节细胞增殖和细胞周期从G（0）/G（1）期向S期和G（2）/M期的转变。我们的研究结果强调了丹皮酚在调节PH受试者PASMCs增殖中的中心作用。因此，丹皮酚代表了一种潜在的治疗PH的新方法。
Pulmonary hypertension (PH) is a disease with a developmental origin characterized by obstructive vascular remodelling that is partially due to excessive pulmonary arterial smooth muscle cells (PASMCs) proliferation. Paeonol has important effects on vascular cell proliferation, migration, and inflammation, but researchers have not determined whether paeonol participates in the development and progression of pulmonary vascular remodelling. We explored the remarkable anti-proliferative effects of paeonol on hypoxic PASMCs, which are postulated to be mediated by the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway. In this study, hypoxic rodent PH models, Western blotting, flow cytometry, immunochemistry, and morphometric analyses of the lung vasculature and right ventricle (RV) vessels were performed. Paeonol reversed hypoxia-induced increases in right ventricular function, right ventricular systolic pressure and thickening of medial walls. Meanwhile, paeonol ameliorated the hypoxia-induced PASMCs proliferation. Furthermore, paeonol modulated cell proliferation and cell cycle transitions from G(0)/G(1) phase to S phase and G(2)/M phase in an ERK1/2-dependent manner. Our findings emphasize the central function of paeonol in regulating PASMCs proliferation in subjects with PH. Therefore, paeonol represents a potential novel therapeutic approach for the treatment of PH.