ArticleBritish journal of pharmacology2017
Inhibiting thyrotropin/insulin-like growth factor 1 receptor crosstalk to treat Graves' ophthalmopathy: studies in orbital fibroblasts in vitro.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Insulin-like Growth Factor Signaling Promotes Corneal Myofibroblast Survival and Sustains Corneal Fibrosis.International journal of molecular sciences · 2026Article
- Advances of IGF-1R inhibitors in Graves' ophthalmopathy.International ophthalmology · 2024Review
- PAPP-A as a Potential Target in Thyroid Eye Disease.The Journal of clinical endocrinology and metabolism · 2024Article
- Graves disease: latest understanding of pathogenesis and treatment options.Nature reviews. Endocrinology · 2024Review
- A Comprehensive Review of Thyroid Eye Disease Pathogenesis: From Immune Dysregulations to Novel Diagnostic and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- The changing landscape of thyroid eye disease: current clinical advances and future outlook.Eye (London, England) · 2024Review
- Article
- Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway.International journal of molecular sciences · 2023Article
- Mechanisms in Graves Eye Disease: Apoptosis as the End Point of Insulin-Like Growth Factor 1 Receptor Inhibition.Thyroid : official journal of the American Thyroid Association · 2022Article
- The risk factors for Graves' ophthalmopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Review
- Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease.The Journal of clinical endocrinology and metabolism · 2022Article
- Cytokines in Thyroid-Associated Ophthalmopathy.Journal of immunology research · 2022Review
- Proximity ligation assay to study TSH receptor homodimerization and crosstalk with IGF-1 receptors in human thyroid cells.Frontiers in endocrinology · 2022Article
- Expression and Role of Thyrotropin Receptors in Proopiomelanocortin-Producing Pituitary Cells.Thyroid : official journal of the American Thyroid Association · 2021Article
- Cytokines as Targets of Novel Therapies for Graves' Ophthalmopathy.Frontiers in endocrinology · 2021Review
- Targeting TSH and IGF-1 Receptors to Treat Thyroid Eye Disease.European thyroid journal · 2020Article
- Is There Evidence for IGF1R-Stimulating Abs in Graves' Orbitopathy Pathogenesis?International journal of molecular sciences · 2020Review
- TSH/IGF1 receptor crosstalk: Mechanism and clinical implications.Pharmacology & therapeutics · 2020Review
- Arrestin-β-1 Physically Scaffolds TSH and IGF1 Receptors to Enable Crosstalk.Endocrinology · 2019Article
- Immunological Aspects of Graves' Ophthalmopathy.BioMed research international · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeCrosstalk between thyrotropin (TSH) receptors and insulin-like growth factor 1 (IGF-1) receptors initiated by activation of TSH receptors could be important in the development of Graves' ophthalmopathy (GO). Specifically, TSH receptor activation alone is sufficient to stimulate hyaluronic acid (HA) secretion, a major component of GO, through both IGF-1 receptor-dependent and -independent pathways. Although an anti-IGF-1 receptor antibody is in clinical trials, its effectiveness depends on the relative importance of IGF-1 versus TSH receptor signalling in GO pathogenesis. EXPERIMENTAL APPROACH: TSH and IGF-1 receptor antagonists were used to probe TSH/IGF-1 receptor crosstalk in primary cultures of Graves' orbital fibroblasts (GOFs) following activation with monoclonal TSH receptor antibody, M22. Inhibition of HA secretion following TSH receptor stimulation was measured by modified HA elisa. KEY
resultsTSH receptor antagonist, ANTAG3 (NCGC00242364), inhibited both IGF-1 receptor -dependent and -independent pathways at all doses of M22; whereas IGF-1 receptor antagonists linsitinib and 1H7 (inhibitory antibody) lost efficacy at high M22 doses. Combining TSH and IGF-1 receptor antagonists exhibited Loewe additivity within the IGF-1 receptor-dependent component of the M22 concentration-response. Similar effects were observed in GOFs activated by autoantibodies from GO patients' sera. CONCLUSIONS AND IMPLICATIONS: Our data support TSH and IGF-1 receptors as therapeutic targets for GO, but reveal putative conditions for anti-IGF-1 receptor resistance. Combination treatments antagonizing both receptors yield additive effects by inhibiting crosstalk triggered by TSH receptor stimulatory antibodies. Combination therapy may be an effective strategy for dose reduction and/or compensate for any loss of anti-IGF-1 receptor efficacy.
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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.