Pigment epithelium-derived factor reduces the PDGF-induced migration and proliferation of human aortic smooth muscle cells through PPARγ activation.
Pigment epithelium-derived factor reduces the PDGF-induced migration and proliferation of human aortic smooth muscle cells through PPARγ activation.
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DOI：
10.1016/j.biocel.2011.10.023
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发表时间：
2012-02
期刊：
影响因子：
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通讯作者：
Shu-Huei Wang;chan-Jung liang;Jiahn‐Chun Wu;Jiuan-Jiuan Huang-Jiuan;H. Chien;Jaw-Shiun Tsai;Yu-Hsiu Yen;Ying-Chih Tseng;J. Lue;Yuh-Lien Chen
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文献类型：
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作者：
Shu-Huei Wang;chan-Jung liang;Jiahn‐Chun Wu;Jiuan-Jiuan Huang-Jiuan;H. Chien;Jaw-Shiun Tsai;Yu-Hsiu Yen;Ying-Chih Tseng;J. Lue;Yuh-Lien Chen
我们的前期研究表明，色素上皮衍生因子（PEDF）在人主动脉平滑肌细胞（HASMCs）的增殖和迁移中起重要作用。在本研究中，我们研究了PEDF是否抑制血小板衍生生长因子（PDGF）刺激的HASMC迁移和增殖。PEDF剂量依赖性地降低PDGF诱导的HASMC迁移和增殖，并将细胞周期进程阻滞在G 0/G1期，这与细胞周期蛋白D1、细胞周期蛋白E、CDK 2、CDK 4和p21 Cip 1表达降低以及细胞周期蛋白依赖性激酶抑制剂p27 Kip 1表达增加有关。PEDF的抗增殖和抗迁移作用可被PPARγ拮抗剂GW 9662部分阻断，但不能被PPARα拮抗剂MK 886阻断。在体内研究中，将C57 BL/6小鼠的股动脉内皮剥脱，并将小鼠静脉内注射PEDF或载体。2周后，新生内膜/中膜面积比和新生内膜中的细胞增殖（增殖细胞核抗原阳性细胞）均显著降低，并且这些作用再次被GW 9662预处理部分逆转。我们的数据表明，PEDF增加了PPARγ的激活，阻止了体外HASMCs进入细胞周期，并减少了体内新生内膜面积和新生内膜中的细胞增殖。因此，PEDF可能是预防和治疗血管增生性疾病的一个安全有效的新靶点。
Our previous study demonstrated that pigment epithelium-derived factor (PEDF) plays an important role in the proliferation and migration of human aortic smooth muscle cells (HASMCs). In the present study, we examined whether PEDF inhibited platelet-derived growth factor (PDGF)-stimulated HASMC migration and proliferation. PEDF dose-dependently reduced PDGF-induced HASMC migration and proliferation in vitro and also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21Cip1and increased expression of the cyclin-dependent kinase inhibitor p27Kip1. The antiproliferative and antimigratory effects of PEDF were partially blocked by the PPARγ antagonist GW9662, but not by the PPARα antagonist MK886. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice injected intravenously with PEDF or vehicle. After 2 weeks, both the neointima/media area ratio and cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima were significantly reduced and again these effects were partially reversed by GW9662 pretreatment. Our data show that PEDF increases PPARγ activation, preventing entry of HASMCs into the cell cycle in vitro and reducing the neointimal area and cell proliferation in the neointima in vivo. Thus, PEDF may represent a safe and effective novel target for the prevention and treatment of vascular proliferative diseases.