Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells.

Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells.
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DOI:
10.1016/j.bbrc.2010.01.123
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发表时间:
2010-03-05
影响因子:
3.1
通讯作者:
Kohn, Leonard D.
Kohn, Leonard D.
中科院分区:
生物学4区
文献类型:
--
作者:
Suzuki, Koichi;Kimura, Hiroaki;Wu, Huhehasi;Kudo, Naoko;Kim, Won Bae;Suzuki, Sayuri;Yoshida, Akio;Caturegli, Patrizio;Kohn, Leonard D.

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虽然众所周知,过量的碘抑制体内甲状腺功能和血流,但其潜在的分子机制尚不完全清楚。碘的功能作用发生在多个步骤,包括抑制钠/碘同向转运体(NIS)的表达,短暂阻断有机化,抑制激素释放。血管效应可能涉及抑制血管内皮生长因子(VEGF)基因。在这份报告中,我们表明过量的碘协同抑制FRTL-5甲状腺细胞中NIS和VEGF基因的表达。我们还表明,碘抑制NIS基因表达的机制是转录,这是协同甲状腺球蛋白的加入。基于报告基因分析和电泳凝胶迁移率变动分析的结果,我们还报告了两个新的DNA结合蛋白,特异性地响应碘化物和调制NIS启动子活性。结果表明,过量碘影响甲状腺血管功能,除了碘的吸收。这项研究为过量碘对甲状腺功能的作用机制提供了额外的见解。
Although it is well known that an excess of iodide suppresses thyroid function and blood flow in vivo, the underlying molecular mechanisms are not fully known. The functional effect of iodide occurs at multiple steps, which include inhibition of sodium/iodide symporter (NIS) expression, transient block of organification, and inhibition of hormonal release. The vascular effect likely involves suppression of the vascular endothelial growth factor (VEGF) gene. In this report, we show that excess iodide coordinately suppresses the expression of the NIS and VEGF genes in FRTL-5 thyroid cells. We also demonstrate that the mechanism of iodide suppression of NIS gene expression is transcriptional, which is synergized by the addition of thyroglobulin. Based on the findings of reporter gene assays and electrophoretic gel mobility shift analysis, we also report two novel DNA binding proteins that responded specifically to iodide and modulated NIS promoter activity. The results suggest that excess iodide affects thyroid vascular function in addition to iodide uptake. This study provides additional insights into the mechanism of action of excess iodide on thyroid function.
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