ArticleInvestigative ophthalmology & visual science2019
TSHR Signaling Stimulates Proliferation Through PI3K/Akt and Induction of miR-146a and miR-155 in Thyroid Eye Disease Orbital Fibroblasts.
Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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The trial behind it
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
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Pooled it
- Efficacy and safety ofFrontiers in pharmacology · 2025Pooled it
- Identification and Validation of Biomarkers in the Development and Progression of Graves' Ophthalmopathy.Investigative ophthalmology & visual science · 2026Article
- MicroRNAs in thyroid eye disease: expression signatures and clinical implications.Frontiers in immunology · 2026Review
- The therapeutic revolution in thyroid eye disease: from orbital radiotherapy to teprotumumab and AI.Frontiers in medicine · 2026Review
- Transcriptomic profiling of thyroid eye disease orbital fibroblasts identifies sorafenib as a novel therapeutic.Frontiers in endocrinology · 2026Article
- Epigenetic Mechanisms in Autoimmune Thyroid Diseases: Bridging Research and Clinical Applications.International journal of molecular sciences · 2025Review
- Redefining Treatment Paradigms in Thyroid Eye Disease: Current and Future Therapeutic Strategies.Journal of clinical medicine · 2025Review
- Thyroid hormone signaling in ocular development and diseases.Biological research · 2025Review
- Identification of key extracellular proteins as the potential biomarkers in thyroid eye disease.PloS one · 2025Article
- Network pharmacology and experiments verify the effect of triptolide on extraocular muscle fibrosis.PloS one · 2025Article
- Role of Lysyl Oxidase-Like Protein 3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.Investigative ophthalmology & visual science · 2024Article
- Tapinarof, an Aryl Hydrocarbon Receptor Ligand, Mitigates Fibroblast Activation in Thyroid Eye Disease: Implications for Novel Therapy.Investigative ophthalmology & visual science · 2024Article
- A Comprehensive Review of Thyroid Eye Disease Pathogenesis: From Immune Dysregulations to Novel Diagnostic and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Employing a synergistic bioinformatics and machine learning framework to elucidate biomarkers associating asthma with pyrimidine metabolism genes.Respiratory research · 2024Article
- Plasma miRNA-146b-3p, -222-3p, -221-5p, -21a-3p Expression Levels andInternational journal of molecular sciences · 2024Article
- Article
- The Role of Fibrogenesis and Extracellular Matrix Proteins in the Pathogenesis of Graves' Ophthalmopathy.International journal of molecular sciences · 2024Review
- Unlocking potential biomarkers bridging coronary atherosclerosis and pyrimidine metabolism-associated genes through an integrated bioinformatics and machine learning approach.BMC cardiovascular disorders · 2024Article
- Environmental pollutants and phosphoinositide signaling in autoimmunity.Journal of hazardous materials · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: To investigate the molecular pathways that drive thyroid stimulating hormone receptor (TSHR)-induced cellular proliferation in orbital fibroblasts (OFs) from thyroid eye disease (TED) patients. Methods: Orbital fibroblasts from TED and non-TED patients were treated with TSH and changes in gene expression and proliferation were measured. To determine the role of TSHR, TSHR-specific siRNA was used to deplete TSHR levels. Proliferation was measured by bromodeoxyuridine (BrdU) incorporation. PI3K/Akt activation was analyzed by Western blot. The PI3K inhibitor LY294002 was used to investigate PI3K/Akt signaling in OF proliferation. Expression of TSHR, inflammatory cytokines, proliferation related genes and miR-146a and miR-155 were measured by qPCR. Results: Orbital fibroblasts from TED patients proliferate significantly more than non-TED OFs in response to TSH. TSH-induced proliferation was dependent upon TSHR expression and required the PI3K/Akt signaling cascade. TSHR activation stimulated miR-146a and miR-155 expression. TED OFs produced significantly more miR-146a and miR-155 than non-TED OFs. MiR-146a and miR-155 targets, ZNRF3 and PTEN, which both limit cell proliferation, were decreased in TSH treated OFs. Conclusions: These data reveal that TSHR signaling in TED OFs stimulates proliferation directly through PI3K/Akt signaling and indirectly through induction of miR-146a and miR-155. MiR-146a and miR-155 enhance TED OF proliferation by reducing expression of target genes that normally block cell proliferation. TSHR-dependent expression of miR-146a and miR-155 may explain part of the fibroproliferative pathology observed in TED.
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Registered trials
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.