Graves' thyroid tissue has been shown to express elevated levels of human sodium/iodide symporter (hNIS) mRNA and protein. In the present work, we demonstrate for the first time that hNIS gene expression in Graves' disease (GD) is up-regulated by Graves' IgG. Here, in transient transfection experiments using FRTL-5 cells, hNIS promoter and enhancer/luciferase construct showed an up to six-fold increase in transcriptional activity after incubation with purified Graves' IgG. Mutation of a CRE site in hNIS enhancer inhibited Graves' IgG response. In addition, mutation of a novel putative regulatory region in hNIS promoter reduced the stimulation three-fold. This discovered putative regulatory sequence might play a role in hNIS up-regulation by Graves' IgG and TSH. The data presented here complement our current knowledge of the pathogenesis of GD and will contribute to a better understanding of mechanisms regulating the thyroid iodide concentrating activity. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
机构:Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, England
Ajjan, RA
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Kamaruddin, NA
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机构:Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, England
Kamaruddin, NA
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Crisp, M
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机构:Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, England
Crisp, M
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Watson, PF
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Ludgate, M
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Weetman, AP
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, England
机构:Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, England
Ajjan, RA
;
Kamaruddin, NA
论文数: 0引用数: 0
h-index: 0
机构:Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, England
Kamaruddin, NA
;
Crisp, M
论文数: 0引用数: 0
h-index: 0
机构:Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, England
Crisp, M
;
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h-index:
机构:
Watson, PF
;
论文数: 引用数:
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机构:
Ludgate, M
;
Weetman, AP
论文数: 0引用数: 0
h-index: 0
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Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, EnglandUniv Sheffield, No Gen Hosp, Ctr Clin Sci, Dept Med, Sheffield S5 7AU, S Yorkshire, England