{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T06:36:37Z","timestamp":1778999797049,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_153062, 31003A_182105, IZSEZ0_193623 and IZCOZ0_177070"],"award-info":[{"award-number":["31003A_153062, 31003A_182105, IZSEZ0_193623 and IZCOZ0_177070"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Leenaards Foundation","award":["2016 Fellowship for Academic Promotion in Clinical Medicine"],"award-info":[{"award-number":["2016 Fellowship for Academic Promotion in Clinical Medicine"]}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["CA16112"],"award-info":[{"award-number":["CA16112"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Section\/Board of Endocrinology of the European Union of Medical Specialists (UEMS)","award":["Exchange in Endocrinology Expertise (3E) Fellowship"],"award-info":[{"award-number":["Exchange in Endocrinology Expertise (3E) Fellowship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Thyroid follicular cells have physiologically high levels of reactive oxygen species because oxidation of iodide is essential for the iodination of thyroglobulin (Tg) during thyroid hormone synthesis. Thyroid follicles (the functional units of the thyroid) also utilize incompletely understood autoregulatory mechanisms to defend against exposure to excess iodide. To date, no transcriptomic studies have investigated these phenomena in vivo. Nuclear erythroid factor 2 like 2 (Nrf2 or Nfe2l2) is a transcription factor that regulates the expression of numerous antioxidant and other cytoprotective genes. We showed previously that the Nrf2 pathway regulates the antioxidant defense of follicular cells, as well as Tg transcription and Tg iodination. We, thus, hypothesized that Nrf2 might be involved in the transcriptional response to iodide overload. Methods: C57BL6\/J wild-type (WT) or Nrf2 knockout (KO) male mice were administered regular water or water supplemented with 0.05% sodium iodide for seven days. RNA from their thyroids was prepared for next-generation RNA sequencing (RNA-Seq). Gene expression changes were assessed and pathway analyses were performed on the sets of differentially expressed genes. Results: Analysis of differentially expressed messenger RNAs (mRNAs) indicated that iodide overload upregulates inflammatory-, immune-, fibrosis- and oxidative stress-related pathways, including the Nrf2 pathway. Nrf2 KO mice showed a more pronounced inflammatory\u2013autoimmune transcriptional response to iodide than WT mice. Compared to previously published datasets, the response patterns observed in WT mice had strong similarities with the patterns typical of Graves\u2019 disease and papillary thyroid carcinoma (PTC). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) also responded to iodide overload, with the latter targeting mRNAs that participate mainly in inflammation pathways. Conclusions: Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves\u2019 disease) and PTC.<\/jats:p>","DOI":"10.3390\/antiox9090884","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T07:27:33Z","timestamp":1600414053000},"page":"884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Transcriptomic Response of the Murine Thyroid Gland to Iodide Overload and the Role of the Nrf2 Antioxidant System"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6139-6067","authenticated-orcid":false,"given":"Dionysios V.","family":"Chartoumpekis","sequence":"first","affiliation":[{"name":"Service of Endocrinology and Diabetology, Lausanne University Hospital, and Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Division of Endocrinology, Department of Internal Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panos G.","family":"Ziros","sequence":"additional","affiliation":[{"name":"Service of Endocrinology and Diabetology, Lausanne University Hospital, and Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3641-1488","authenticated-orcid":false,"given":"Ilias","family":"Georgakopoulos-Soares","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA"},{"name":"Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4593-3042","authenticated-orcid":false,"given":"Adam A. T.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Claudia","family":"Marques","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, University of Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Ibberson","sequence":"additional","affiliation":[{"name":"Vital-IT Group, Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"A. Kopp","sequence":"additional","affiliation":[{"name":"Service of Endocrinology and Diabetology, Lausanne University Hospital, and Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Habeos","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-2772","authenticated-orcid":false,"given":"Ioannis P.","family":"Trougakos","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas K. H.","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9565-4941","authenticated-orcid":false,"given":"Gerasimos P.","family":"Sykiotis","sequence":"additional","affiliation":[{"name":"Service of Endocrinology and Diabetology, Lausanne University Hospital, and Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1210\/me.2011-0038","article-title":"Regulation of thyroid oxidative state by thioredoxin reductase has a crucial role in thyroid responses to iodide excess","volume":"25","author":"Leoni","year":"2011","journal-title":"Mol. 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