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Innovation Promotion Association CAS","award":["2020K02"],"award-info":[{"award-number":["2020K02"]}]},{"name":"Youth Innovation Promotion Association CAS","award":["2021YFA1100500"],"award-info":[{"award-number":["2021YFA1100500"]}]},{"name":"Youth Innovation Promotion Association CAS","award":["91957205"],"award-info":[{"award-number":["91957205"]}]},{"name":"Youth Innovation Promotion Association CAS","award":["82070821"],"award-info":[{"award-number":["82070821"]}]},{"name":"Youth Innovation Promotion Association CAS","award":["82270828"],"award-info":[{"award-number":["82270828"]}]},{"name":"Youth Innovation Promotion Association CAS","award":["21PJ1416100"],"award-info":[{"award-number":["21PJ1416100"]}]},{"name":"Youth Innovation Promotion Association CAS","award":["2021261"],"award-info":[{"award-number":["2021261"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Iodine is an essential micronutrient for producing thyroid hormone (TH); however, iodide excess can lead to adverse thyroidal effects. Unfortunately, the lack of a proper in vitro model system hampered the studies of the effect of iodide excess on thyroid physiology and pathology. Here, we demonstrated that excessive iodide intake downregulated the genes related to TH synthesis in the thyroids of mice. Since sodium iodide has no effect on these genes in cultured cell lines, we developed a three-dimensional (3D) culture system to enable the murine thyrocytes to form organoids in vitro with thyroid follicle-like structures and function and found that the in vivo effect of iodide excess could be mimicked in these thyroid organoids. Our data indicate that iodide excess mainly activated the XBP1-mediated unfolded protein response in both murine thyroid and thyroid organoids, while activation of XBP1 was able to mimic the sodium iodide effect on genes for the synthesis of TH in murine thyroid organoids. Lastly, our results suggest that XBP1 might transcriptionally repress the genes involved in the synthesis of TH. Based on these findings, we propose that iodide excess inhibits the transcription of genes related to TH synthesis through a mechanism involving XBP1-mediated action.<\/jats:p>","DOI":"10.3390\/nu15040887","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T05:18:35Z","timestamp":1676006315000},"page":"887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Iodide Excess Inhibits Thyroid Hormone Synthesis Pathway Involving XBP1-Mediated Regulation"],"prefix":"10.3390","volume":"15","author":[{"given":"Jing","family":"Yu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai 200233, China"},{"name":"Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Shen","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai 200233, China"},{"name":"Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yan","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai 200233, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongkui","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Liu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital, Shanghai 200233, 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