ArticleThe Journal of clinical endocrinology and metabolism2012
A stimulatory thyrotropin receptor antibody enhances hyaluronic acid synthesis in graves' orbital fibroblasts: inhibition by an IGF-I receptor blocking antibody.
Article in The Journal of clinical endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 84 citations in OpenAlex.
- TSHR-Targeting Nucleic Acid Aptamer Treats Graves' Ophthalmopathy via Novel Allosteric Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The impact of graves' orbitopathy on anterior segment structures and choroidal parameters.BMC ophthalmology · 2025Article
- Clinical Phenotype of Graves Disease in Autoimmune Polyglandular Syndrome or as Isolated Disease: The GRAPHE Study.The Journal of clinical endocrinology and metabolism · 2025Observational
- Article
- PAPP-A as a Potential Target in Thyroid Eye Disease.The Journal of clinical endocrinology and metabolism · 2024Article
- Epidemiology of thyroid-stimulating immunoglobulin in recent-onset symptomatic thyroid eye disease.European thyroid journal · 2024Article
- Effect of orbital decompression surgery on the choroidal profile in patients with thyroid eye disease.Scientific reports · 2024Article
- Impact of ibrutinib on inflammation in a mouse model of Graves' orbitopathy.Frontiers in endocrinology · 2024Article
- Article
- The Potential of Artemisinins as Novel Treatment for Thyroid Eye Disease by Inhibiting Adipogenesis in Orbital Fibroblasts.Investigative ophthalmology & visual science · 2023Article
- The risk factors for Graves' ophthalmopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Review
- Proximity ligation assay to study TSH receptor homodimerization and crosstalk with IGF-1 receptors in human thyroid cells.Frontiers in endocrinology · 2022Article
- Local immune microenvironment of skin may play an important role in the development of pretibial myxedema.Experimental dermatology · 2021Article
- Prognostic factors of restrictive myopathy in thyroid eye disease.Scientific reports · 2021Article
- Transcriptomic Profiling of Control and Thyroid-Associated Orbitopathy (TAO) Orbital Fat and TAO Orbital Fibroblasts Undergoing Adipogenesis.Investigative ophthalmology & visual science · 2021Article
- Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease.BMJ case reports · 2021Article
- Targeting TSH and IGF-1 Receptors to Treat Thyroid Eye Disease.European thyroid journal · 2020Article
- Thyroid-Stimulating Hormone Receptor Autoimmunity and Local Factors in Multiple Risk Factors Are Mainly Involved in the Occurrence of Pretibial Myxedema.Journal of clinical medicine research · 2020Article
- TSH/IGF1 receptor crosstalk: Mechanism and clinical implications.Pharmacology & therapeutics · 2020Review
- TSHR Signaling Stimulates Proliferation Through PI3K/Akt and Induction of miR-146a and miR-155 in Thyroid Eye Disease Orbital Fibroblasts.Investigative ophthalmology & visual science · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
contextGraves' ophthalmopathy (GO) is characterized by expanded volume of the orbital fat and extraocular muscle tissues and elevated levels of TSH receptor autoantibodies (TRAb). The expansion of orbital tissues involves accumulation of hyaluronic acid (HA) within the orbit.
objectiveThe objective of the study was to determine whether a monoclonal stimulatory TRAb (M22) impacts HA synthesis in GO orbital cells and, if so, whether this might be blocked by an IGF-I receptor (IGF-IR)-blocking antibody (1H7) or inhibitors of various downstream signaling cascades.
designGO orbital fibroblast cultures (n = 6) were treated with M22, bovine TSH (bTSH), or IGF-I in serum-free medium. Some cultures also received 1H7, LY294002, rapamycin, or protein kinase A inhibitor.
main outcome measuresHA production and phosphorylated Akt levels in media or immunoblotting for phosphorylated Akt were measured.
resultsM22 or bTSH stimulated HA synthesis (2.1-fold with 100 ng/ml M22 and 1.9-fold with 10 U/liter bTSH; P < 0.05 each). M22-induced HA synthesis was inhibited by LY294002 or rapamycin but not by protein kinase inhibitor. HA synthesis stimulated by M22 or IGF-I was inhibited by 1H7 (mean 36.6 ± 5.6% and mean 45.8 ± 7.6%, respectively; P < 0.05 each). Similarly, M22- or IGF-I-stimulated Akt phosphorylation was inhibited by 1H7 (mean 54 ± 9.6 and 36.1 ± 8.8%, respectively; P = 0.01 each).
conclusionsThe stimulatory TRAb M22 increases HA production in undifferentiated GO orbital fibroblasts via phosphoinositide 3-kinase/phosphorylated AKT/mammalian target of rapamycin activation. Blockade of IGF-IR inhibits both HA synthesis and Akt phosphorylation induced by M22 or IGF-I in these cells, suggesting that TSH receptor and IGF-IR signaling may be closely linked in the GO orbit.
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