Department of Pathophysiology, Harbin Medical University, 157, Baojian Road, Harbin, 150081, China.
Department of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Mol Cell Biochem. 2018 Mar;440(1-2):157-165. doi: 10.1007/s11010-017-3164-0. Epub 2017 Aug 21.
Vascular smooth muscle cells (VSMCs) proliferation is a key process in atherosclerosis. However, little is known about the underlying mechanisms, leading to a lack of effective therapy. This study was to investigate whether dopamine receptor 1 (DR1) is involved in the VSMCs proliferation and related mechanisms. A7r5 cells were treated with oxidized low-density lipoprotein (ox-LDL, 10, 20, 50, 100, 200 µg/mL) in the presence or absence of the SKF38393 (DR1agonist), SCH23390 (DR1antiagonist), SP600125 (JNK inhibitor), PD98059(ERK1/2 inhibitor) or NAC (ROS inhibitor). Cell proliferation and related signaling pathway were evaluated. The expression of DR1 was negatively correlated with increasing of cell proliferation caused by ox-LDL. Cell proliferation and ROS generation in response to ox-LDL were prevented by DR1 agonist or over-expression. The peroxiredoxins protein (Prx1, 2, 3, 5, 6) were increased in A7r5 cells treated with ox-LDL; however, only Prx3 dramatically increased after activation of DR1 compared with ox-LDL group, which is related to activation of JNK/c-Jun pathway. In addition, ERK is associated with the restraining effects of DR1 activation. DR1 activation inhibits VSMCs proliferation primarily by JNK/c-Jun dependent increasing of Prx3, suggesting DR1 a potential target for the prevention of vascular proliferation disease.
血管平滑肌细胞（VSMCs）增殖是动脉粥样硬化的一个关键过程。然而，对于潜在的机制知之甚少，导致缺乏有效的治疗方法。本研究旨在探讨多巴胺受体 1（DR1）是否参与 VSMCs 的增殖及其相关机制。用氧化型低密度脂蛋白（ox-LDL，10、20、50、100、200μg/ml）处理 A7r5 细胞，同时存在或不存在 SKF38393（DR1 激动剂）、SCH23390（DR1 拮抗剂）、SP600125（JNK 抑制剂）、PD98059（ERK1/2 抑制剂）或 NAC（ROS 抑制剂）。评估细胞增殖和相关信号通路。DR1 的表达与 ox-LDL 引起的细胞增殖增加呈负相关。DR1 激动剂或过表达可防止 ox-LDL 引起的细胞增殖和 ROS 生成。在 ox-LDL 处理的 A7r5 细胞中，过氧化物还原酶蛋白（Prx1、2、3、5、6）增加；然而，只有 DR1 激活后 Prx3 明显增加，与 ox-LDL 组相比，这与 JNK/c-Jun 通路的激活有关。此外，ERK 与 DR1 激活的抑制作用有关。DR1 激活主要通过 JNK/c-Jun 依赖性增加 Prx3 来抑制 VSMCs 增殖，提示 DR1 是预防血管增殖性疾病的潜在靶点。
