The Transcriptomic Response of the Murine Thyroid Gland to Iodide Overload and the Role of the Nrf2 Antioxidant System.

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Serval ID
serval:BIB_F9FB94E92E22
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Transcriptomic Response of the Murine Thyroid Gland to Iodide Overload and the Role of the Nrf2 Antioxidant System.
Journal
Antioxidants
Author(s)
Chartoumpekis D.V., Ziros P.G., Georgakopoulos-Soares I., Smith AAT, Marques A.C., Ibberson M., A Kopp P., Habeos I., Trougakos I.P., Khoo NKH, Sykiotis G.P.
ISSN
2076-3921 (Print)
ISSN-L
2076-3921
Publication state
Published
Issued date
18/09/2020
Peer-reviewed
Oui
Volume
9
Number
9
Pages
E884
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
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.
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-autoimmune 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' 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.
Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves' disease) and PTC.
Keywords
Kelch-like ECH-associated protein 1 (Keap1), Nfe2l2, RNA-Seq, fibrosis, immune response, inflammation, iodine, oxidative stress
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation / Projects / 31003A_153062
Swiss National Science Foundation / Projects / 31003A_182105
Swiss National Science Foundation / Projects / IZSEZ0_193623
Swiss National Science Foundation / Projects / IZCOZ0_177070
Fondation Leenaards / 2016 Fellowship for Academic Promotion in Clinical Medicine
Other / European Cooperation in Science and Technology (COST) Action CA16112 (NutRedOx)
Other / Exchange in Endocrinology Expertise (3E) Fellowship
Create date
26/09/2020 16:23
Last modification date
28/12/2020 8:11
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