The presence of adenosine A2a receptor in thyrocytes and its involvement in Graves' IgG-induced VEGF expression.
The presence of adenosine A2a receptor in thyrocytes and its involvement in Graves' IgG-induced VEGF expression.
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甲状腺细胞中腺苷 A2a 受体的存在及其参与 Graves IgG 诱导的 VEGF 表达。
DOI：
10.1210/en.2012-2258
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发表时间：
2013-09
期刊：
影响因子：
4.8
通讯作者：
Gao, Ling
中科院分区：
文献类型：
--
作者：
Zhao, Jiajun;Xu, Jin;Sun, Nannan;Cai, Hu;Ren, Meng;Zhang, Jie;Yu, Chunxiao;Wang, Zhe;Gao, Ling
Graves病（GD）的甲状腺肿发生归因于抗TSH受体抗体刺激。最近，腺苷A2 a受体（A2 aR）在甲状腺球蛋白-A2 aR转基因小鼠甲状腺肿形成中的作用被报道。然而，目前还不清楚A2 aR是否在甲状腺中表达，它是否与GD甲状腺肿的发病机制。在此，我们通过PCR、蛋白质印迹、免疫组织化学和免疫荧光证实了A2 aR在FRTL-5细胞、原代正常人甲状腺细胞（使用两种性别，不考虑性别）和甲状腺组织（使用两种性别，不考虑性别）中的表达。在用A2 aR特异性激动剂2-对-（2-羧乙基）苯乙氨基-5 '-N-乙基羧酰胺腺苷或GD IgG处理后，血管内皮生长因子（VEGF）（一种与甲状腺肿发生相关的生长因子）的mRNA和蛋白水平与上游信号通路一起被评价沿着。A2 aR激活和GD IgG促进甲状腺细胞VEGF表达，并伴随cAMP/蛋白激酶A/磷酸化cAMP反应元件结合蛋白、过氧化物酶体增殖物激活受体γ共激活因子-1 α和缺氧诱导因子-1 α的激活。GD IgG引起的变化被A2 aR小干扰RNA和A2 aR拮抗剂部分消除。这些结果得到了来自促甲状腺素受体腺病毒诱导的GD小鼠模型（雌性）的甲状腺肿样品数据的支持。这些数据表明GD IgG可以通过A2 aR上调VEGF表达，表明GD中甲状腺肿发生的潜在机制。
Goitrogenesis in Graves' disease (GD) has been attributed to anti-TSH receptor antibody stimulation. Recently, a role for adenosine A2a receptor (A2aR) in goiter formation was reported in the thyroglobulin-A2aR transgenic mice. However, it is unclear whether A2aR is expressed in the thyroid and whether it is associated with the pathogenesis of goiter in GD. Here, we confirmed the expression of A2aR in FRTL-5 cells, primary normal human thyrocytes (both sexes were used without regard to sex), and thyroid tissue (both sexes were used without regard to sex) by PCR, Western blotting, immunohistochemistry, and immunofluorescence. After treatments with A2aR-specific agonist 2-p-(2-Carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine or GD IgG, the mRNA and protein levels of vascular endothelial growth factor (VEGF), a growth factor related to goitrogenesis, were evaluated along with upstream signaling pathways. A2aR activation and GD IgG promoted the expression of VEGF in thyrocytes, which was accompanied by the activation of cAMP/protein kinase A/phosphorylated-cAMP-response element-binding protein, peroxisome proliferator-activated receptor γ coactivator-1α, and hypoxia-inducible factor-1α. The changes induced by GD IgG were partially abrogated by A2aR small interfering RNA and an A2aR antagonist. These results were supported by data on the goiter samples from the thyrotropin receptor adenovirus-induced GD mouse model (female). These data demonstrate that GD IgG could up-regulate the VEGF expression through A2aR, indicating a potential mechanism for goitrogenesis in GD.
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影响因子：
1.5
作者：
E. Otten
通讯作者：
E. Otten
DOI：
10.1172/jci17069
发表时间：
2003-06
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Chun‐Rong Chen;P. Pichurin;Y. Nagayama;F. Latrofa;B. Rapoport;S. McLachlan
通讯作者：
Chun‐Rong Chen;P. Pichurin;Y. Nagayama;F. Latrofa;B. Rapoport;S. McLachlan
影响因子：
11.5
作者：
Nomura, Takeo;Huang, Wen-Chin;Chung, Leland W. K.
通讯作者：
Chung, Leland W. K.
影响因子：
6.1
作者：
B. Ahrén;A. Gustafson;P. Hedner
通讯作者：
B. Ahrén;A. Gustafson;P. Hedner
DOI：
10.1210/jcem.77.1.8100833
发表时间：
1993-07
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Y. Shoda;Y. Kondo;I. Kobayashi
通讯作者：
Y. Shoda;Y. Kondo;I. Kobayashi