Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium.

Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium.
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DOI:
10.1038/sj.bjc.6602503
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发表时间:
2005-04-25
影响因子:
8.8
通讯作者:
Atkin, SL
Atkin, SL
中科院分区:
医学1区
文献类型:
--
作者:
Adams, RL;Adams, IP;Lindow, SW;Zhong, W;Atkin, SL

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血管生成以内皮细胞的激活、迁移和增殖为特征,是癌症、心血管疾病和慢性炎症病理的核心。生长抑素是一种通过五种受体(sst 1、2、3、4、5)发挥作用的抑制性多肽。SST在血管内皮细胞中的作用已有报道,但其作用尚不清楚。在此,我们报道了sst在体外培养的人脐静脉内皮细胞(HUVECs)增殖和静止时的表达。建立了增殖和静止期人脐静脉内皮细胞的培养方法,并用流式细胞术分析了细胞周期分布。然后用定量逆转录聚合酶链式反应对9个增殖和静止的HUVEC中的SST mRNA进行定量。SST2和SST5在增殖期HUVECs中优先表达。所有标本SST4均为阴性,SST1和SST3表达与细胞周期进展无关。Sst-2和sst-5的免疫染色在增殖的细胞中呈阳性,但在静止的细胞中不表达,证实了sst-2和sst-5蛋白的表达。具有生长抑素5活性的生长抑素类似物奥曲肽和SOM230对细胞增殖的抑制作用呈剂量依赖性(奥曲肽10−10-10−6 M:48.5-70.2%;SOM230 10−9-10−6 M:44.9-65.4%),提示SST 5可能具有促增殖作用。SST2和SST5在细胞周期中表达的动态变化以及特定类似物对增殖的抑制表明这些受体可能在血管生成中起作用。
Angiogenesis is characterised by activation, migration and proliferation of endothelial cells and is central to the pathology of cancer, cardiovascular disease and chronic inflammation. Somatostatin is an inhibitory polypeptide that acts through five receptors (sst 1, 2, 3, 4, 5). Sst has previously been reported in endothelium, but their role remains obscure. Here, we report the expression of sst in human umbilical vein endothelial cells (HUVECs) in vitro, during proliferation and quiescence. A protocol for culturing proliferating and quiescent HUVECs was established, and verified by analysing cell cycle distribution in propidium-iodide-stained samples using flow cytometry. Sst mRNA was then quantified in nine proliferating and quiescent HUVEC lines using quantitative reverse transcriptase–polymerase chain reaction. Sst 2 and 5 were preferentially expressed in proliferating HUVECs. All samples were negative for sst 4. Sst 1 and 3 expression and cell cycle progression were unrelated. Immunostaining for sst 2 and 5 showed positivity in proliferating but not quiescent cells, confirming sst 2 and 5 protein expression. Inhibition of proliferating cells with somatostatin analogues Octreotide and SOM230, which have sst 5 activity, was found (Octreotide 10−10–10−6 M: 48.5–70.2% inhibition; SOM230 10−9–10−6 M: 44.9–65.4% inhibition) in a dose-dependent manner, suggesting that sst 5 may have functional activity in proliferation. Dynamic changes in sst 2 and 5 expression during the cell cycle and the inhibition of proliferation with specific analogues suggest that these receptors may have a role in angiogenesis.
DOI: 10.1016/s0026-0495(96)90080-3
发表时间: 1996-08-01
影响因子: 9.8
作者:
Danesi, R;DelTacca, M
通讯作者: DelTacca, M
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发表时间: 2003-04-01
期刊: ENDOCRINOLOGY
影响因子: 4.8
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DOI: 10.1016/s0928-4257(00)00214-x
发表时间: 2000-05-01
影响因子: --
作者:
Florio, T;Thellung, S;Stork, PJS
通讯作者: Stork, PJS