Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves’ orbitopathy

Pawłowski, Przemysław; Poplawska, Izabela; Myśliwiec, Janusz; Dik, Willem A.; Eckstein, Anja; Berchner‐Pfannschmidt, Utta; Milewski, Robert; Ławicki, Sławomir; Dzięcioł-Anikiej, Zofia; Ręjdak, Robert; Reszeć, Joanna

doi:10.5603/fhc.a2020.0003

Cited by 6 publications

(3 citation statements)

References 32 publications

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“…IGF-1R is another autoantigen involved in the pathogenesis of TED [ 11 , 69 ]. Recent studies have reported that expression of the IGF-1R protein is higher in orbital tissue from TED patients than in that from controls [ 70 , 71 ]. However, despite the fact that many previous studies confirmed the involvement of IGF-1R in TED, activation of IGF-1R on OFs after binding by stimulating antibodies (IGF-1R-Ab) remains controversial [ 56 ].…”

Section: Pathogenesismentioning

confidence: 99%

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Immunological Processes in the Orbit and Indications for Current and Potential Drug Targets

Cieplińska,

Niedziela,

Kowalska

2023

JCM

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Thyroid eye disease (TED) is an extrathyroidal manifestation of Graves’ disease (GD). Similar to GD, TED is caused by an autoimmune response. TED is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, swelling, redness, conjunctivitis, and bulging eyes. The pathophysiology of TED is complex, with the infiltration of activated T lymphocytes and activation of orbital fibroblasts (OFs) and autoantibodies against the common autoantigen of thyroid and orbital tissues. Better understanding of the multifactorial pathogenesis of TED contributes to the development of more effective therapies. In this review, we present current and potential drug targets. The ideal treatment should slow progression of the disease with as little interference with patient immunity as possible. In the future, TED treatment will target the immune mechanism involved in the disease and will be based on a strategy of restoring tolerance to autoantigens.

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Section: Pathogenesismentioning

confidence: 99%

“…High serum levels of BAFF were reported in patients with TED [ 72 ]. Expression of the BAFF protein in the orbital tissue of TED patients is higher than that in healthy controls [ 71 ].…”

Section: Pathogenesismentioning

confidence: 99%

Immunological Processes in the Orbit and Indications for Current and Potential Drug Targets

Cieplińska,

Niedziela,

Kowalska

2023

JCM

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show abstract

“… 20 Several studies have implicated the inflammatory process in the manifestation of TAO. 21 , 22 In fact, the NLRP3 inflammasome is known to activate interleukin (IL) 1B, 23 which in turn stimulates an increase of hyaluronan accumulation in OFs 24 and also increases levels of IL-6 and prostaglandin E2. 20 , 25 …”

Section: Introductionmentioning

confidence: 99%

MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy

Tang¹,

Liu²,

Huang³

et al. 2022

JIR

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Objective Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact mechanism is unclear. We investigated whether IGF-1R/TSHR modulation in TAO may involve microRNA regulation. Methods We conducted microarray analysis using RNA from the orbital connective tissue samples of 3 healthy and 3 patients with TAO. The involvement of differentially regulated microRNA in IGF-1R/TSHR modulation in TAO was evaluated in orbital fibroblasts (OFs) and female BALB/c mice. Results Using hierarchical cluster analysis, we identified that miR-143 was downregulated in TAO. The expression levels of miR-143 in OFs were significantly reduced under IL-1B stimulation. However, OF proliferation and inflammatory responses decreased when miR-143 is overexpressed. In contrast, the suppression of miR-143 increased levels of inflammatory markers (IL-6, IL-8, MCP1) and hyaluronan accumulation. Moreover, overexpression of miR-143 significantly lowers levels of IGF-1R and TSHR. A luciferase assay indicated that miR-143 targets the 3′-UTR of IGF-1R. Increases in the expression of IGF-1R increased the expression of the inflammasome marker NLRP3 and apoptotic marker cleaved caspase-1; however, miR-143 overexpression decreased levels of IGF-1R, TSHR, NLRP3, cleaved caspase 1, IL-1B, and IL-18. In a mouse model of TAO, overexpression of miR-143 significantly reduced levels of IGF-1R and attenuated the adipogenesis associated with TAO. Conclusion We found that miR-143 directly targets IGF-1R to alleviate the inflammatory response in TAO by indirectly decreasing levels of TSHR and inactivating NLRP3.

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Redox mechanisms in autoimmune thyroid eye disease

Buonfiglio,

Ponto,

Pfeiffer

et al. 2024

Autoimmunity Reviews

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Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves’ orbitopathy

Cited by 6 publications

References 32 publications

Immunological Processes in the Orbit and Indications for Current and Potential Drug Targets

Immunological Processes in the Orbit and Indications for Current and Potential Drug Targets

MiR-143 Targets IGF-1R to Suppress Autoimmunity in Thyroid-Associated Ophthalmopathy

Redox mechanisms in autoimmune thyroid eye disease

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