Effects of TSH on the function of human umbilical vein endothelial cells
Effects of TSH on the function of human umbilical vein endothelial cells
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TSH对人脐静脉内皮细胞功能的影响
DOI：
10.1530/jme-13-0119
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发表时间：
2014-04-01
影响因子：
3.5
通讯作者：
Ni, Jing
中科院分区：
文献类型：
--
作者：
Tian, Limin;Zhang, Luyan;Ni, Jing
近年来研究发现亚临床甲状腺功能减退症（subclinical hypothyroidism，SCH）与动脉粥样硬化（atherosclerosis，AS）有关。SCH患者的甲状腺激素维持在正常水平，而TSH升高。然而，AS与SCH相关的发病机制仅部分了解。此外，内皮功能障碍在AS的发展中起重要作用。本研究旨在探讨促甲状腺激素（TSH）对人脐静脉内皮细胞（HUVECs）的直接作用。分别采用实时PCR和蛋白质印迹法检测促甲状腺激素治疗后与内皮功能障碍相关的一些基因的表达。首先，我们发现TSH受体（TSHR）在HUVECs中表达。我们还提供了证据表明，促甲状腺激素治疗促进肿瘤坏死因子α诱导的内皮细胞的相互作用，通过上调表达的粘附分子细胞间粘附分子-1。促甲状腺激素（TSH）处理后，内皮型一氧化氮合酶（eNOS）和前列环素（PGI（2））的表达明显降低，且呈剂量和时间依赖性。结果显示，TSH可上调内皮素1（ET 1）mRNA和蛋白表达，不同浓度TSH对内皮素1（ET 1）和纤溶酶原激活物抑制物1（PAI 1）的作用相似。总而言之，这些结果表明，TSH升高可以通过改变HUVEC中的基因表达来促进内皮功能障碍。
Recent studies have reported that subclinical hypothyroidism (SCH) is associated with atherosclerosis (AS). Thyroid hormone is maintained at normal levels in patients with SCH, whereas TSH is increased. However, the pathogenesis of AS in association with SCH is only partially understood. In addition, endothelial dysfunction plays an important role in the development of AS. The purpose of the present research was to study the direct effect of TSH on human umbilical vein endothelial cells (HUVECs). The expression of some genes associated with endothelial dysfunction after treatment with TSH was evaluated by real-time PCR and western blotting respectively. At first, we showed that the TSH receptor (TSHR) is expressed in HUVECs. We also provide evidence indicating that TSH treatment promotes tumor necrosis factor alpha-induced endothelial cells interactions by upregulating the expression of the adhesion molecules intercellular adhesion molecule-1. Furthermore, the expression of endothelial nitric oxide synthase (eNOS) and prostacyclin (PGI(2)) was significantly attenuated following treatment with TSH in dose- and time-dependent manner. Conversely, the results indicated that TSH upregulated endothelin-1 (ET1) mRNA and protein expression in HUVECs, similar effects were observed for plasminogen activator inhibitor-1 (PAI1) after treatment with various concentrations of TSH. Taken together, these results demonstrate that elevated TSH can promote endothelial dysfunction by altering gene expression in HUVECs.