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Citations to this article

Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats
Warner S. Simonides, … , Antonio C. Bianco, Stephen A. Huang
Warner S. Simonides, … , Antonio C. Bianco, Stephen A. Huang
Published February 7, 2008
Citation Information: J Clin Invest. 2008;118(3):975-983. https://doi.org/10.1172/JCI32824.
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Research Article Endocrinology Article has an altmetric score of 4

Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats

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Abstract

Thyroid hormone is a critical determinant of cellular metabolism and differentiation. Precise tissue-specific regulation of the active ligand 3,5,3′-triiodothyronine (T3) is achieved by the sequential removal of iodine groups from the thyroid hormone molecule, with type 3 deiodinase (D3) comprising the major inactivating pathway that terminates the action of T3 and prevents activation of the prohormone thyroxine. Using cells endogenously expressing D3, we found that hypoxia induced expression of the D3 gene DIO3 by a hypoxia-inducible factor–dependent (HIF-dependent) pathway. D3 activity and mRNA were increased both by hypoxia and by hypoxia mimetics that increase HIF-1. Using ChIP, we found that HIF-1α interacted specifically with the DIO3 promoter, indicating that DIO3 may be a direct transcriptional target of HIF-1. Endogenous D3 activity decreased T3-dependent oxygen consumption in both neuronal and hepatocyte cell lines, suggesting that hypoxia-induced D3 may reduce metabolic rate in hypoxic tissues. Using a rat model of cardiac failure due to RV hypertrophy, we found that HIF-1α and D3 proteins were induced specifically in the hypertrophic myocardium of the RV, creating an anatomically specific reduction in local T3 content and action. These results suggest a mechanism of metabolic regulation during hypoxic-ischemic injury in which HIF-1 reduces local thyroid hormone signaling through induction of D3.

Authors

Warner S. Simonides, Michelle A. Mulcahey, Everaldo M. Redout, Alice Muller, Marian J. Zuidwijk, Theo J. Visser, Frank W.J.S. Wassen, Alessandra Crescenzi, Wagner S. da-Silva, John Harney, Felix B. Engel, Maria-Jesús Obregon, P. Reed Larsen, Antonio C. Bianco, Stephen A. Huang

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 3 4 12 4 9 4 14 7 6 9 5 9 4 7 10 4 5 5 121
Citation information
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Citations to this article in year 2022 (4)

Title and authors Publication Year
Triiodothyronine (T3), inflammation and mortality risk in patients with acute myocardial infarction
Razvi S, Jabbar A, Bano A, Ingoe L, Carey P, Junejo S, Thomas H, Addison C, Austin D, Greenwood JP, Zaman AG
European Thyroid Journal 2022
The interplay of thyroid hormones and the immune system - where we stand and why we need to know about it.
Wenzek C, Boelen A, Westendorf AM, Engel DR, Moeller LC, Führer D
European Journal of Endocrinology 2022
Role of miR-133/Dio3 Axis in the T3-Dependent Modulation of Cardiac mitoK-ATP Expression
Canale P, Nicolini G, Pitto L, Kusmic C, Rizzo M, Balzan S, Iervasi G, Forini F
International journal of molecular sciences 2022
Plateau Adaptation Gene Analyses Reveal Transcriptomic, Proteomic, and Dual Omics Expression in the Lung Tissues of Tibetan and Yorkshire Pigs.
Shang P, Zhang B, Li P, Ahmed Z, Hu X, Chamba Y, Zhang H
2022

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