Huang Huibin, Shi Yaxiong, Liang Bo, Cai Huiyao, Cai Qingyan
Department of Endocrinology, The Second affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, Fujian, 362000, People's Republic of China.
Biol Trace Elem Res. 2017 Dec;180(2):206-213. doi: 10.1007/s12011-017-1017-z. Epub 2017 Apr 10.
Our previous research has suggested that high degree of iodinated thyroglobulin (TG) may inhibit the expression and function of sodium iodide symporter (NIS), but the underlying mechanism remains unclear. In present study, we discuss a newly constructed follicle model in vitro, which was used to simulate the follicular structure of the thyroid and explore the regulatory roles of iodinated TG in the follicular lumen on NIS expression. The results showed that both NIS expression and PKA activity were increased in lowly iodinated TG group, while decreased NIS expression with increased PKC activity was found in highly iodinated TG group. Also, NIS expression was increased in PKA agonist-treated group, while decreased NIS was found in PKC agonist-treated group. Moreover, when the PLC-PKC pathway was blocked by PKC-specific inhibitor, highly iodinated TG significantly promoted the expression of NIS. However, when the cAMP-PKA pathway was blocked by a PKA-specific blocker, highly iodinated TG slightly suppressed NIS expression. TG with a low degree of iodination had the reverse effect on NIS. When the PLC-PKC pathway was blocked, TG with a low degree of iodination slightly promoted NIS expression. However, when the cAMP-PKA pathway was blocked, TG with a low degree of iodination greatly inhibited NIS expression. All these suggested that iodinated TG inhibited the expression of NIS by PLC-PKC pathway and promoted NIS expression via the cAMP-PKA pathway. When highly iodinated TG was present, the PLC-PKC pathway became dominant. In the presence of lowly iodinated TG, the cAMP-PKA became the major pathway.
我们之前的研究表明，高碘化甲状腺球蛋白（TG）可能会抑制钠碘同向转运体（NIS）的表达和功能，但其潜在机制仍不清楚。在本研究中，我们探讨了一种新构建的体外滤泡模型，该模型用于模拟甲状腺的滤泡结构，并探究滤泡腔内碘化TG对NIS表达的调节作用。结果显示，低碘化TG组中NIS表达和PKA活性均增加，而高碘化TG组中NIS表达降低且PKC活性增加。此外，PKA激动剂处理组中NIS表达增加，而PKC激动剂处理组中NIS表达降低。而且，当PLC-PKC途径被PKC特异性抑制剂阻断时，高碘化TG显著促进NIS的表达。然而，当cAMP-PKA途径被PKA特异性阻滞剂阻断时，高碘化TG轻微抑制NIS表达。低碘化TG对NIS有相反的作用。当PLC-PKC途径被阻断时，低碘化TG轻微促进NIS表达。然而，当cAMP-PKA途径被阻断时，低碘化TG极大地抑制NIS表达。所有这些表明，碘化TG通过PLC-PKC途径抑制NIS的表达，并通过cAMP-PKA途径促进NIS表达。当存在高碘化TG时，PLC-PKC途径占主导地位。当存在低碘化TG时，cAMP-PKA成为主要途径。
