DR1 activation reduces the proliferation of vascular smooth muscle cells by JNK/c-Jun dependent increasing of Prx3

作者：Chen, Junting; Shi, Sa; Cai, Xiaona; Li, Hongzhu; Wang, Lina; Li, Hong; Xu, Changqing^*

来源：Molecular and Cellular Biochemistry, 2018, 440(1-2): 157-165.

DOI：10.1007/s11010-017-3164-0

• Dopamine receptor
• VSMCs
• Proliferation
• Peroxiredoxins
• Ox-LDL

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 A mu g/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.

• 出版日期2018-3
• 单位哈尔滨医科大学