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Review
. 2021 Nov 9:12:739994.
doi: 10.3389/fendo.2021.739994. eCollection 2021.

Orbital Signaling in Graves' Orbitopathy

Mohd Shazli Draman  1   2 , Lei Zhang  1 , Colin Dayan  1 , Marian Ludgate  1
Affiliations
Review

Orbital Signaling in Graves' Orbitopathy

Mohd Shazli Draman et al. Front Endocrinol (Lausanne). .

Abstract

Graves' orbitopathy (GO) is a complex and poorly understood disease in which extensive remodeling of orbital tissue is dominated by adipogenesis and hyaluronan production. The resulting proptosis is disfiguring and underpins the majority of GO signs and symptoms. While there is strong evidence for the thyrotropin receptor (TSHR) being a thyroid/orbit shared autoantigen, the insulin-like growth factor 1 receptor (IGF1R) is also likely to play a key role in the disease. The pathogenesis of GO has been investigated extensively in the last decade with further understanding of some aspects of the disease. This is mainly derived by using in vitro and ex vivo analysis of the orbital tissues. Here, we have summarized the features of GO pathogenesis involving target autoantigens and their signaling pathways.

Keywords: IGF1R; TSAB; TSHR; adipogenesis; hyaluronan; thyroid eye disease.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Cartoon summarizing orbital fibroblast signaling cascades in Graves’ orbitopathy (GO) and how they affect pathogenetic mechanisms (adipogenesis and hyaluronan production). TSHR/TRAB and IGFR/IGF are shown in red with arrows indicating the possible crosstalk between the pathways in GO. thyrotropin receptor (TSHR, serpentine structure); TSHR auto-antibodies (TRAB); Insulin-like growth factor 1 receptor (IGF-1R) and IGF1; protein kinase A (PKA); protein kinase B (PKB/Akt); protein kinase C (PKC); phosphoinositide 3-kinase (PI3K); forkhead box protein O (FOXO); hyaluronan production (HA).
See this image and copyright information in PMC

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