Different effects of neuropeptide Y on proliferation of vascular smooth muscle cells via regulation of Geminin
Different effects of neuropeptide Y on proliferation of vascular smooth muscle cells via regulation of Geminin
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神经肽Y通过Geminin调节对血管平滑肌细胞增殖的不同影响
DOI：
10.1007/s11010-017-3028-7
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发表时间：
2017-09-01
影响因子：
4.3
通讯作者：
Shu，Mao-qin
中科院分区：
文献类型：
--
作者：
Jiang，Zhou-qin;Zhou，You-li;Shu，Mao-qin
神经肽Y（NPY）的促增殖作用始终在低血清培养的血管平滑肌细胞（VSMC）中发挥作用，并且VSMC的表型转换受血清浓度调节。 VSMCs中NPY增殖效应的性质是否依赖于VSMCs的表型尚不清楚。我们的目的是探讨 NPY 对不同 VSMC 表型增殖在动脉粥样硬化发病机制中的作用。通过用 0.5 或 10% 血清中的 200 nM NPY 刺激 A10 细胞，使用 3H-胸苷和 5-乙炔基-2'-脱氧尿苷 (EdU) 和 CCK8 测量来检测 VSMC 增殖。采用RT-PCR和流式细胞术检测VSMCs中NPY增殖效应不同特性所涉及的因素。当在 10% 血清中培养时，NPY 不会促进增殖，而是对 VSMC 的生长没有显着影响（VSMC 保持合成状态）。潜在机制可能涉及在与 200 nM NPY 共孵育的 10% 血清培养 VSMC 中 Y1 受体下调（相对于载体，P<0.05）和 Geminin 上调（相对于载体，P<0.05）。此外，Geminin 的调节可被 Y1 受体拮抗剂有效阻断。 NPY对VSMCs增殖的刺激可能是动脉粥样硬化发展过程中的一把双刃剑，从而为动脉粥样硬化的治疗提供了新的知识。
The proliferation-promoting effect of neuropeptide Y (NPY) always functions in low-serum-cultured vascular smooth muscle cells (VSMCs), and the phenotypic switch of VSMCs is regulated by concentrations of serum. Whether the property of the NPY proliferative effect in VSMCs relies on phenotype of VSMCs is unclear. We aimed to explore the role of NPY on proliferation of different VSMC phenotypes in the pathogenesis of atherosclerosis. By stimulating A10 cells with 200 nM NPY in 0.5 or 10% serum, 3H-thymidine and 5-ethynyl-2′-deoxyuridine (EdU) and CCK8 measurements were used to detect VSMC proliferation. RT-PCR and Flow cytometry were performed to detect the factors involved in different properties of the NPY proliferative effect in VSMCs. Instead of facilitating proliferation, NPY had no significant effect on the growth of VSMCs when cultured in 10% serum (VSMCs stayed at synthetic states). The underlying mechanism may be involved in down-regulation of Y1 receptor (P< 0.05 vs. Vehicle) and up-regulation of Geminin (P< 0.05 vs. Vehicle) in 10% serum-cultured VSMCs co-incubated with 200 nM NPY. Besides, modulation of Geminin was effectively blocked by the Y1 receptor antagonist. The stimulation of NPY on proliferation of VSMCs could be a double-edged sword in the development of atherosclerosis and thus provides new knowledge for therapy of atherosclerosis.