Thyroid hormone induces cardiac myocyte hypertrophy in a thyroid hormone receptor α1-specific manner that requires TAK1 and p38 mitogen-activated protein kinase

Kinugawa, Koichiro; Jeong, Mark Y.; Bristow, Michael R.; Long, Carlin S.

doi:10.1210/me.2004-0503

Cited by 80Thyroid Disorders and TreatmentsCardiac Fibrosis and RemodelingEstrogen and related hormone effects

Thyroid hormone induces cardiac myocyte hypertrophy in a thyroid hormone receptor α1-specific manner that requires TAK1 and p38 mitogen-activated protein kinase

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Kinugawa, Koichiro, Jeong, Mark Y., Bristow, Michael R., Long, Carlin S.·2005·Molecular Endocrinology

DOI 10.1210/me.2004-0503PMC PMC1237131

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Abstract

Alterations in TR [thyroid hormone (TH) receptor]1 isoform expression have been reported in models of both physiologic and pathologic cardiac hypertrophy as well as in patients with heart failure. In this report, we demonstrate that TH induces hypertrophy as a direct result of binding to the TRalpha1 isoform and, moreover, that overexpression of TRalpha1 alone is also associated with a hypertrophic phenotype, even in the absence of ligand. The mechanism of TH and TRalpha1-specific hypertrophy is novel for a nuclear hormone receptor and involves the transforming growth factor beta-activated kinase (TAK1) and p38. Mitigating TRalpha1 effects, both TRalpha2 and TRbeta1 attenuate TRalpha1-induced myocardial growth and gene expression by diminishing TAK1 and p38 activities, respectively. These findings refine our previous observations on TR expression in the hypertrophied and failing heart and suggest that manipulation of thyroid hormone signaling in an isoform-specific manner may be a relevant therapeutic target for altering the pathologic myocardial program.

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From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [28]

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Regulation of Thyroid Hormone Receptor Isoforms in Physiological and Pathological Cardiac Hypertrophy
Kinugawa, K., Yonekura, K., Ribeiro, R. C. J., Eto, Y., Aoyagi, T., Baxter, J. D., Camacho, S. A., Bristow, M. R., Long, C. S., & Simpson, P. C. (2001) · Circulation Research · doi:10.1161/hh1901.096706 · Cited by 199 · see citing works
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Authors: Kinugawa, K., Jeong, M. Y., Bristow, M. R., & Long, C. S.
Affiliations: Denver Health Medical Center (US)
Division of Cardiology (M.R.B., C.S.L.), Denver, Colorado 80204
Corresponding author: Long, Carlin S.
ORCID: Kinugawa, Koichiro
Jeong, Mark Y.
Bristow, Michael R.
Long, Carlin S.
Venue: Molecular Endocrinology
Publisher: The Endocrine Society
Published: 2005-06-01
Volume: 19
Issue: 6
Pages: 1618-1628
ISSN: 0888-8809 (ISSN-L)
1944-9917
DOI: 10.1210/me.2004-0503
PMC: PMC1237131
OpenAlex: W2133338733
Cited by: 80
References: 48
Citations by year: 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 7 · 2015: 1 · 2014: 7 · 2013: 1 · 2012: 4
FWCI: 3.75
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Molecular Endocrinology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs
University of California, San Diego
University of California, San Francisco
National Heart, Lung, and Blood Institute (R01HL066399)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords: thyroid hormones, cardiomyocyte hypertrophy, thyroid hormone receptor alpha 1, TRα2, thyroid hormone receptor beta 1, TAK1, p38 MAPK, heart failure, ligand-independent receptor activation
MeSH terms: MAP Kinase Kinase Kinase 7, Adenoviridae, Animals, Cell Nucleus, Cells, Cultured, Cytosol, Dose-Response Relationship, Drug, Enzyme Inhibitors, Humans, Hypertrophy, Imidazoles, Ligands, Microscopy, Fluorescence, Models, Biological, Myocardium, Protein Binding, Pyridines, Rabbits, Receptors, Thyroid Hormone, Ribonucleases, Thyroid Hormones, Time Factors, Blotting, Western, Signal Transduction, DNA, Complementary, Protein Isoforms, Inhibitory Concentration 50, MAP Kinase Kinase Kinases, Muscle Cells, Myocytes, Cardiac, Thyroid Hormone Receptors alpha, Immunoprecipitation, p38 Mitogen-Activated Protein Kinases, Cell Proliferation, Rats

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Thyroid hormone induces cardiac myocyte hypertrophy in a thyroid hormone receptor α1-specific manner that requires TAK1 and p38 mitogen-activated protein kinase

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