Mechanism of the divergent effects of estrogen on the cell proliferation of human umbilical endothelial Versus aortic smooth muscle cells
Mechanism of the divergent effects of estrogen on the cell proliferation of human umbilical endothelial Versus aortic smooth muscle cells
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DOI：
10.1210/en.2007-0188
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发表时间：
2007-12-01
期刊：
影响因子：
4.8
通讯作者：
Kurachi, Hirohisa
中科院分区：
文献类型：
--
作者：
Kawagoe, Jun;Ohmichi, Masahide;Kurachi, Hirohisa
不同的雌激素作用通过雌激素受体（ER）控制。ER的作用机制受到多种因素的调节，例如ER亚型、ER-配体复合物的构象以及辅调节因子复合物向靶基因启动子的募集。雌激素对血管细胞发挥不同的作用;即它增加内皮细胞和抑制平滑肌细胞生长，导致血管保护作用。我们特别关注这些不同的影响，并检查了机制。雷洛昔芬，这表明雌激素样血管保护作用的影响，也进行了检查。为了检测17 β-雌二醇（E-2）和雷洛昔芬对人主动脉平滑肌细胞（HASMCs）和人脐静脉内皮细胞（HUVECs）的影响，我们评价了E-2和雷洛昔芬对IGF-I和考克斯-2基因转录活性、辅调节复合物向靶基因启动子的募集以及组蛋白乙酰化的影响。用E-2或雷洛昔芬治疗增加了HUVEC中IGF-I和环氧合酶（考克斯）-2 mRNA的表达，而它们减弱了HASMCs中这些基因的血清诱导的增加。E2和雷洛昔芬处理诱导HUVECs共激活因子复合物的募集和IGF-I和考克斯-2基因启动子的组蛋白乙酰化。相比之下，在HASMC中，E2和雷洛昔芬减弱了血清诱导的辅激活因子复合物的募集以及IGF-I和考克斯-2基因启动子处的组蛋白乙酰化。雌激素和雷洛昔芬对HUVECs和HASMCs中IGF-1和考克斯-2基因启动子的mRNA表达和重塑发挥不同的转录调节作用。
Diverse estrogen actions are controlled via estrogen receptors (ERs). Mechanisms of action of ERs are modulated by various factors such as ER subtypes, conformation of the ER-ligand complex, and recruitment of coregulator complexes to a target gene promoter. Estrogen exerts divergent actions on vascular cells; namely it increases endothelial cell and inhibits smooth muscle cell growth, resulting in a vasoprotective action. We particularly focused on these divergent effects and examined the mechanisms. The effects of raloxifene, which shows estrogenlike vasoprotective actions, were also examined. To examine the effects of 17 beta-estradiol (E-2) and raloxifene on human aortic smooth muscle cells (HASMCs) and human umbilical venous endothelial cells (HUVECs), we evaluated the effect of E-2 and raloxifene on transcriptional activity, recruitment of the coregulator complex to a target gene promoter, and acetylation of histone of both the IGF-I and COX-2 genes. Treatment with E-2 or raloxifene increased both IGF-I and cyclooxygenase (COX)-2 mRNA expression in HUVECs, whereas they attenuated the serum-induced increase of these genes in HASMCs. Treatment by E2 and raloxifene induced recruitment of coactivator complex and histone acetylation at both the IGF-I and COX-2 gene promoter in HUVECs. In contrast, in HASMCs, E2, and raloxifene attenuated the seruminduced recruitment of coactivator complexes and histone acetylation at both the IGF-I and COX-2 gene promoters. Estrogen and raloxifene exert divergent transcriptional regulation on both mRNA expression and the remodeling of IGF-I and COX-2 gene promoters in HUVECs vs. HASMCs.