Dopamine D₄ receptors inhibit proliferation and migration of vascular smooth muscle cells induced by insulin via down-regulation of insulin receptor expression.
Dopamine D₄ receptors inhibit proliferation and migration of vascular smooth muscle cells induced by insulin via down-regulation of insulin receptor expression.
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多巴胺D-4受体通过下调胰岛素受体表达抑制胰岛素诱导的血管平滑肌细胞增殖和迁移
DOI：
10.1186/1475-2840-13-97
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发表时间：
2014-06-02
影响因子：
9.3
通讯作者：
Zeng C
中科院分区：
文献类型：
--
作者：
Yu C;Wang Z;Han Y;Liu Y;Wang WE;Chen C;Wang H;Jose PA;Zeng C
血管平滑肌细胞（VSMCs）的增殖和迁移受多种激素和体液因子的调节，在血管疾病的发生发展中起着重要作用。胰岛素受体的激活刺激VSMCs增殖，而多巴胺受体通过D1和D3受体抑制去甲肾上腺素对VSMCs增殖的刺激作用。我们推测多巴胺D4受体的激活也可能抑制VSMCs的增殖和迁移，从而抑制动脉粥样硬化。我们目前的研究发现，胰岛素增加了A10细胞的增殖和迁移，这种作用在D4受体激动剂PD 168077的存在下降低。D4受体对胰岛素作用的负面影响可能是通过降低胰岛素受体的表达，因为D4受体的激活抑制胰岛素受体蛋白和mRNA的表达，表明这种调节发生在转录或转录后水平。为了确定D4受体对胰岛素介导的VSMC增殖和迁移的抑制是否具有生理意义，用D4激动剂PD 168077（6 mg/kg/d）治疗颈动脉球囊损伤的高胰岛素血症Sprague-Dawley大鼠14天。我们发现PD 168077通过抑制VSMC增殖显著抑制新生内膜形成。提示D4受体的激活可抑制血管平滑肌细胞的增殖和迁移，从而抑制动脉粥样硬化的发生。D4受体可能是一个潜在的治疗靶点，以减少胰岛素对动脉重塑的影响。
Vascular smooth muscle cells (VSMCs) proliferation and migration, which are central in the development of vascular diseases, are regulated by numerous hormones and humoral factors. Activation of the insulin receptor stimulates VSMCs proliferation while dopamine receptors, via D1 and D3 receptors, inhibit the stimulatory effects of norepinephrine on VSMCs proliferation. We hypothesize that activation of the D4 dopamine receptor may also inhibit the proliferation and migration of VSMCs, therefore, inhibit atherosclerosis. Our current study found that insulin increased the proliferation and migration of A10 cells, an effect that was reduced in the presence of a D4 receptor agonist, PD168077. The negative effect of the D4 receptor on insulin’s action may be via decreasing insulin receptor expression, because activation of the D4 receptor inhibited insulin receptor protein and mRNA expressions, indicating that the regulation occured at the transcriptional or post-transcriptional levels. To determine whether or not the inhibition of D4 receptor on insulin-mediated proliferation and migration of VSMCs has physiological significance, hyper-insulinemic Sprague–Dawley rats with balloon-injured carotid artery were treated with a D4 agonist, PD168077, (6 mg/kg/d) for 14 days. We found that PD168077 significantly inhibited neointimal formation by inhibition of VSMC proliferation. This study suggests that activation of the D4 receptor suppresses the proliferation and migration of VSMCs, therefore, inhibit atherosclerosis. The D4 receptor may be a potential therapeutic target to reduce the effects of insulin on artery remodeling.
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影响因子：
5.4
作者：
Tsuchida, H;Imai, G;Owada, S
通讯作者：
Owada, S
GRK4 在高血压动脉 AT1 受体调节中的作用
影响因子：
8.3
作者：
Chen, Ken;Fu, Chunjiang;Zeng, Chunyu
通讯作者：
Zeng, Chunyu
影响因子：
4.8
作者：
Rubí, B;Ljubicic, S;Maechler, P
通讯作者：
Maechler, P
影响因子：
2.3
作者：
Horita, Shoko;Seki, George;Fujita, Toshiro
通讯作者：
Fujita, Toshiro
影响因子：
4.2
作者：
Mastrogiannis, Dimitrios S.;Spiliopoulos, Michail;Homko, Carol J.
通讯作者：
Homko, Carol J.