Iodide inhibits vascular endothelial growth factor-A expression in cultured human thyroid follicles: a microarray search for effects of thyrotropin and iodide on angiogenesis factors.
Iodide inhibits vascular endothelial growth factor-A expression in cultured human thyroid follicles: a microarray search for effects of thyrotropin and iodide on angiogenesis factors.
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DOI：
10.1089/thy.2006.16.545
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发表时间：
2006-07
期刊：
影响因子：
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通讯作者：
E. Yamada;K. Yamazaki;K. Takano;T. Obara;Kanji Sato
中科院分区：
文献类型：
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作者：
E. Yamada;K. Yamazaki;K. Takano;T. Obara;Kanji Sato
目的为减少术中出血和渗漏，甲状腺功能亢进症患者术前应给予高碘。本研究的目的是阐明碘减少高血管甲状腺血流量的机制。设计人甲状腺滤泡在促甲状腺激素(TSH)存在或不存在的情况下，或在含有不同浓度碘的培养液中培养人甲状腺滤泡，用基因芯片分析促甲状腺激素或碘调节的基因表达。主要结果促甲状腺激素刺激甲状腺球蛋白、过氧化物酶、钠碘转运体、血管内皮生长因子-A、血管内皮生长因子-B和胎盘生长因子的表达，但使血管内皮生长因子-C的表达降低一半。高碘(10(5)M)培养的甲状腺滤泡，TSH诱导的血管内皮生长因子-A、血管内皮生长因子-B和前列腺素F的表达减少，同时分泌的血管内皮生长因子-A减少。此外，可能的血管生成抑制物，如尿激酶型纤溶酶原激活物(PLAU)的表达增加。实时定量聚合酶链式反应和Northern印迹杂交证实了上述发现。结论首次证实高浓度碘可降低血管生成因子VEGF-A、VEGF-B和PGF的表达，同时增加PLAU等可能的抗血管生成因子的表达。这些促血管生成因子和抗血管生成因子可能至少部分解释了碘引起的甲状腺血流量下降。
OBJECTIVE Excess iodide has been administered to hyperthyroid patients before thyroid surgery to reduce intraoperative bleeding and oozing. The purpose of this study was to elucidate the mechanism by which iodide reduces blood flow in the hypervascular thyroid gland. DESIGN Human thyroid follicles were cultured in the presence or absence of thyrotropin (TSH), or in medium containing various concentrations of iodide, and TSH-or iodide-regulated gene expression was analyzed by cDNA microarray. MAIN OUTCOME TSH stimulated the expression of thyroglobulin, peroxidase, sodium iodide symporter, vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PGF) but decreased that of VEGF-C by half. When thyroid follicles were cultured in high-iodide (10(5) M) medium, TSH-induced expression of VEGF-A, VEGF-B, and PGF was decreased, accompanied by a reduction of VEGF-A release into the medium. Furthermore, expression of putative angiogenesis inhibitors such as urokinase-type plasminogen activator (PLAU) was increased. These findings were confirmed by real-time polymerase chain reaction (PCR) and Northern blot hybridization. CONCLUSIONS We have demonstrated for the first time that iodide at high concentration decreases the expression of the angiogenic factors VEGF-A, VEGF-B, and PGF, accompanied by an increase in the expression of possible antiangiogenic factors such as PLAU. These proangiogenic and antiangiogenic factors may at least partly account for the iodide-induced decrease in thyroid blood flow.