ArticleProceedings of the National Academy of Sciences of the United States of America2016
Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Obesity facts · 2024Guideline
- TMetabolic brain disease · 2026Article
- Navigating thyroid hormone signaling in liver fibrosis: mechanisms and clinical implications.Journal of endocrinological investigation · 2026Review
- Early BAL microRNA Signatures Delineate Biological Trajectories Towards CLAD After Lung Transplantation.Cells · 2026Article
- Frozen Shoulder as a Systemic Immunometabolic Disorder: The Roles of Estrogen, Thyroid Dysfunction, Endothelial Health, Lifestyle, and Clinical Implications.Journal of clinical medicine · 2025Review
- Present and Future Perspectives in the Treatment of Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Thyroid hormone signaling in ocular development and diseases.Biological research · 2025Review
- Μetabolic dysfunction-associated steatotic liver disease: a condition of heterogeneous metabolic risk factors, mechanisms and comorbidities requiring holistic treatment.Nature reviews. Gastroenterology & hepatology · 2025Review
- Advances and challenges in kidney fibrosis therapeutics.Nature reviews. Nephrology · 2025Review
- Potential therapeutic impacts of vitamin D on hypothyroid-induced heart and kidney fibrosis and oxidative status in male rat.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH).Nature reviews. Drug discovery · 2025Review
- Triiodothyronine Is Associated with Incidence/Resolution of Steatotic Liver Disease: Longitudinal Study in Euthyroid Korean.Endocrinology and metabolism (Seoul, Korea) · 2025Article
- Thyroid Hormone Action by Genomic and Nongenomic Molecular Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Targeting THR-β for MASLD: Mechanisms and Drug Development.Drug design, development and therapy · 2025Review
- ECM remodeling in hypothyroidism-associated MAFLD: mechanisms, clinical relevance, and therapeutic targets.Frontiers in immunology · 2025Review
- Association of Sensitivity to Thyroid Hormones and Non-Alcoholic Fatty Liver Disease and the Severity of Liver Fibrosis in Euthyroid Adults: A Retrospective Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Actions of thyroid hormones and thyromimetics on the liver.Nature reviews. Gastroenterology & hepatology · 2025Review
- Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC).Nutrition & metabolism · 2024Review
- Thyroid dysfunction in Hashimoto's thyroiditis: a pilot study on the putative role of miR-29a and TGFβ1.Endocrine · 2024Article
- TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA.Nature communications · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize transcriptional activation by TGF-β/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMAD-binding elements in response to TGF-β, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis induced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.