ArticleEuropean thyroid journal2015
DuOx2 Promoter Regulation by Hormones, Transcriptional Factors and the Coactivator TAZ.
Article in European thyroid journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- The role and mechanism of NADPH oxidase in the development and progression of thyroid carcinoma.American journal of cancer research · 2023Review
- Review
- Thyroid hormone receptor β sumoylation is required for thyrotropin regulation and thyroid hormone production.JCI insight · 2021Article
- High Expression of PDE8B and DUOX2 Associated with Ability of Metastasis in Thyroid Carcinoma.Computational and mathematical methods in medicine · 2021Article
- The role of thyroglobulin in thyroid hormonogenesis.Nature reviews. Endocrinology · 2019Review
- Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease.Molecular metabolism · 2019Article
- Paradoxical roles of dual oxidases in cancer biology.Free radical biology & medicine · 2017Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
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Abstract
The production of H2O2, which is essential to thyroid hormone synthesis, involves two NADPH oxidases: dual oxidases 1 and 2 (DuOx1 and DuOx2). A functional study with human DuOx genes and their 5'-flanking regions showed that DuOx1 and -2 promoters are different from thyroid-specific gene promoters. Furthermore, their transcriptional activities are not restricted to thyroid cells. While regulation of Tg (thyroglobulin) and TPO (thyroperoxidase) expression have been extensively studied, DuOx2 promoter regulation by hormones and transcriptional factors need to be more explored. Herein we investigated the role of TSH, insulin and insulin-like growth factor 1 (IGF-1), as well as the cAMP effect on DuOx2 promoter (ptx41) activity in transfected rat thyroid cell lines (PCCL3). We also assessed DuOx2 promoter activity in the presence of transcriptional factors crucial to thyroid development such as TTF-1 (thyroid transcription factor 1), PAX8, CREB, DREAM, Nkx2.5 and the coactivator TAZ in HeLa and HEK 293T-transfected cells. Our results show that TSH and forskolin, which increase cAMP in thyroid cells, stimulated DuOx2 promoter activity. IGF-1 led to pronounced stimulation, while insulin induction was not statistically different from DuOx2 promoter basal activity. All transcriptional factors selected for this work and coactivator TAZ, except DREAM, stimulated DuOx2 promoter activity. Moreover, Nkx2.5 and TAZ synergistically increased DuOx2 promoter activity. In conclusion, we show that DuOx2 expression is regulated by hormones and transcription factors involved in thyroid organogenesis and carcinogenesis, reinforcing the importance of the control of H2O2 generation in the thyroid.
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