Differential gene expression analysis of iodide-treated rat thyroid follicular cell line PCCl3
Open accessAbstract
The inhibitory effect of supraphysiological iodide concentrations on thyroid hormone synthesis (Wolff-Chaikoff effect) and on thyrocyte proliferation is largely known as iodine autoregulation. However, the molecular mechanisms by which iodide modulates thyroid function remain unclear. In this paper, we analyze the transcriptome profile of the rat follicular cell lineage PCCl3 under untreated and treated conditions with 10(-3) M sodium iodide (NaI). Serial analysis of gene expression (SAGE) revealed 84 transcripts differentially expressed in response to iodide (p</=0.001). We also showed that iodide excess inhibits the expression of essential genes for thyroid differentiation: Tshr, Nis, Tg, and Tpo. Relative expression of 14 of 20 transcripts selected by SAGE was confirmed by real-time PCR. Considering the key role of iodide organification in thyroid physiology, we also observed that both the oxidized form of iodide and iodide per se are responsible for gene expression modulation in response to iodide excess.
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High iodide downregulates NIS through inhibition of NIS transcription, shortening of NIS mRNA poly(A) tail and destabilization, and shortening of NIS protein half-life.
“NIS is downregulated by high iodide through several mechanisms. First of all, high iodide inhibits the transcription of NIS (216, 234, 235).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [235]
The Validation of SAGE data section reports that high iodide reduced Nis mRNA expression in PCCl3 cells, supporting NIS downregulation. The paper does not establish that inhibition of NIS transcription, rather than another mechanism affecting mRNA abundance, caused the reduction. The poly(A)-tail and protein-half-life mechanisms are not part of the quoted citing sentence assessed here. (LLM, conf=0.87)
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Research works printed but not linked: 7
- M. Greespan, The thyroid gland, Basic and Clinical Endocrinology, Prentice Hall, London, 1997, pp. 193-262.
- S.H. Ingbar, Autoregulation of the thyroid: response to iodide excess and depletion, Mayo Clin. Proc. 47 (1972) 814-823.
- F.S. Ambesi-Impiombato, L.A. Parks, H.G. Coon, Culture of hormone- dependent functional epithelial cells from rat thyroids, Proc. Natl. Acad. Sci. U. S. A. 77 (1980) 3455-3459.
- C. Vilain, F. Libert, D. Venet, S. Costagliola, G. Vassart, Small amplified RNA-SAGE: an alternative approach to study transcriptome from limiting amount of mRNA, Nucleic Acids Res. 31 (2003) e24.
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- C. Perez-Plasencia, et al., Characterization of the global profile of genes expressed in cervical epithelium by serial analysis of gene expression (SAGE), BMC Genomics 6 (2005) 130.
- J.Y. Lee, et al., Analysis of gene expression profiles of normal human nasal mucosa and nasal polyp tissues by SAGE, J. Allergy Clin. Immunol. 118 (2006) 134-142.
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Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
- Authors
- Leoni, S. G., Galante, P. A., Ricarte-Filho, J. C. M., & Kimura, E. T.
- Affiliations
- Universidade de São Paulo (BR)
- Ludwig Cancer Research (BE)
- Corresponding author
- Kimura, E.T.
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 91
- Issue
- 4
- Pages
- 356-366
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W2086992325
- Cited by
- 41
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2020: 3 · 2019: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Universidade de São Paulo
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
- Keywords
- iodide excess, Wolff-Chaikoff effect, thyroid follicular cells, differential gene expression, thyroid hormone synthesis, thyrocyte proliferation, TSHR, Ni, TG, TPO, gene expression profiling
- MeSH terms
- Animals, Base Sequence, Cell Line, Iodides, RNA, Messenger, Thyroid Gland, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Rats
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