The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thyroid hormones reduce hepatic steatosis by stimulating hepatic lipophagy and mitochondrial biogenesis, and by inhibiting hepatic lipogenesis.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [348]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“They can also interfere with fi brogenesis by inhibiting TGFb signalling.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [348]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Bagnato, G., Bitto, A., Irrera, N., Pizzino, G., Sangari, D., Cinquegrani, M., Roberts, W. N., Atteritano, M., Altavilla, D., Squadrito, F., et al. (2013) · Arthritis Research & Therapy · doi:10.1186/ar4300 · Cited by 19
RetractedBataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958
Massagué, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3434 · Cited by 3,239
Smad transcription factorsPreprint
Massagué, J., Seoane, J., & Wotton, D. (2005) · Genes & Development · doi:10.1101/gad.1350705 · Cited by 2,519
Thyroid Hormone Regulation of Metabolism
Mullur, R., Liu, Y.-Y., & Brent, G. A. (2014) · Physiological Reviews · doi:10.1152/physrev.00030.2013 · Cited by 2,421
TLR4 enhances TGF-β signaling and hepatic fibrosis
Seki, E., De Minicis, S., Österreicher, C. H., Kluwe, J., Osawa, Y., Brenner, D. A., & Schwabe, R. F. (2007) · Nature Medicine · doi:10.1038/nm1663 · Cited by 1,942
SPECIFICITY AND VERSATILITY IN TGF-β SIGNALING THROUGH SMADS
Feng, X.-H., & Derynck, R. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.022404.142018 · Cited by 1,869
Pathogenesis of Liver Fibrosis
Hernandez-Gea, V., & Friedman, S. L. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130246 · Cited by 1,809
TGFβ signals through a heteromeric protein kinase receptor complex
Wrana, J. L., Attisano, L., Cárcamo, J. M., Zentella‐Dehesa, A., Doody, J. F., Laiho, M., Wang, X.-F., & Massagué, J. (1992) · Cell · doi:10.1016/0092-8674(92)90395-s · Cited by 1,528
Liver fibrosis and repair: Immune regulation of wound healing in a solid organ
Pellicoro, A., Ramachandran, P., Iredale, J. P., & Fallowfield, J. A. (2014) · Nature Reviews Immunology · doi:10.1038/nri3623 · Cited by 1,310
Cited by
Sorted by citations
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210
TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis—Updated 2019
Dewidar, B., Meyer, C., Dooley, S., & Meindl-Beinker, A. N. (2019) · Cells · doi:10.3390/cells8111419 · Cited by 837
Targeting metabolic dysregulation for fibrosis therapy
Zhao, X. L., Kwan, J. Y. Y., Yip, K. W., Liu, P. P., & Liu, F. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0040-5 · Cited by 537
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 545
Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function
Yu, G., Τzouvelekis, Α., Wang, R., Herazo‐Maya, J. D., Ibarra, G. H., Srivastava, A., Werneck‐de‐Castro, J. P., DeIuliis, G., Ahangari, F., Woolard, T., et al. (2017) · Nature Medicine · doi:10.1038/nm.4447 · Cited by 360
Metadata
- Authors
- Alonso-Merino, E., Martín Orozco, R., Ruíz-Llorente, L., Martínez-Iglesias, O. A., Velasco-Martín, J. P., Montero-Pedrazuela, A., Fanjul-Rodríguez, L., Contreras-Jurado, C., Regadera, J., & Aranda, A.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Instituto de Investigaciones Biomédicas “Alberto Sols,” Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 20829 Madrid, Spain;
- Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, 20829 Madrid, Spain
- Universidad Autónoma de Madrid (ES)
- Corresponding author
- Aranda, Ana
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-05-31
- Volume
- 113
- Issue
- 24
- Pages
- E3451-60
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4914168
- OpenAlex
- W2409493994
- Cited by
- 108
- References
- 57
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 21 · 2023: 10 · 2022: 9 · 2021: 11 · 2020: 10 · 2019: 13 · 2018: 6 · 2017: 4 · 2016: 3
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Hispana (submittedVersion, other-oa)
- Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, public-domain)
- Funders
- Ministerio de Economía y Competitividad (BFU2011-28058, BFU2014-53610P)
- Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (RD12/0036/0030)
- Comunidad de Madrid (S2011/BMD-2328)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- thyroid hormones, triiodothyronine, TGF-beta signaling, Smad3, SMAD4, thyroid hormone receptor, transcriptional crosstalk, Smad phosphorylation, Smad binding element, histone acetylation, liver fibrosis, carbon tetrachloride, skin fibrosis, bleomycin, collagen deposition, fibrosis
- MeSH terms
- Animals, Bleomycin, Carbon Tetrachloride Poisoning, Liver Cirrhosis, Triiodothyronine, Signal Transduction, Transforming Growth Factor beta, Mice, Knockout, Mice, Smad3 Protein, Smad4 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
