DR1 activation reduces the proliferation of vascular smooth muscle cells by JNK/c-Jun dependent increasing of Prx3
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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.
KeywordsDopamine receptor VSMCs Proliferation Peroxiredoxins Ox-LDL
This work was supported by the National Natural Science Foundation of China Projects (No. 81270311), Heilongjiang Province Natural Science Foundation of China (No. D200880) and Natural Science foundation of Heilongjiang Education Department (No. 12521181).
CX, HL supervised the study. HL, CX and SS participated in study design. HL, SS and JC contributed to the scientific discussion of the data. HL and JC performed the experiments.
Compliance with ethical standards
Conflict of interest
All authors have seen and approved the final manuscript and have taken due care to ensure the integrity of the work. The authors have declared that no conflict of interests exist.
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