Platelet-derived growth factor: a key factor in the pathogenesis of graves' ophthalmopathy and potential target for treatment

European Thyroid Journal
Sita VirakulWillem A Dik

Abstract

Activation of orbital fibroblasts resulting in excessive proliferation, cytokine and hyaluronan production and differentiation into adipocytes, is a main determinant of orbital tissue inflammation and tissue expansion in Graves' ophthalmopathy (GO). During the last years we have shown that the platelet-derived growth factor (PDGF) isoforms PDGF-AA, PDGF-AB and PDGF-BB are increased in orbital tissue from GO patients with active and inactive disease. These PDGF isoforms exhibit the capacity to stimulate proliferation, hyaluronan and cytokine/chemokine production by orbital fibroblasts. Moreover, PDGF-AB and PDGF-BB increase thyroid stimulating hormone receptor (TSHR) expression by orbital fibroblasts, which enhances the orbital fibroblast activating capacity of the THSR stimulatory autoantibodies present in Graves' disease (GD) patients. Of these PDGF isoforms PDGF-BB exhibits the strongest orbital fibroblast activating effects, which is likely related to its ability to bind both the PDGF-receptor (PDGF-R)α and PDGF-Rβ chains. Thus the PDGF-system fulfills important roles in orbital fibroblast activation in both active and inactive GO, which supports a therapeutic rationale for blocking PDGF signaling in GO. Tyrosine kinase inhi...Continue Reading

Citations

Jun 9, 2016·Molecular and Cellular Endocrinology·Sita VirakulWillem A Dik
Jun 28, 2016·The Lancet. Diabetes & Endocrinology·Wilmar M Wiersinga
Feb 7, 2019·Thyroid : Official Journal of the American Thyroid Association·Benjamin SchrijverWillem A Dik
Jan 11, 2020·International Ophthalmology·Jessica M Pouso-DizFrancisco Gonzalez
Oct 29, 2020·Taiwan Journal of Ophthalmology·Yazhuo HuangHuifang Zhou
Jul 9, 2021·Thyroid : Official Journal of the American Thyroid Association·Supanuch EkronarongchaiSita Virakul

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Sita VirakulWillem A Dik
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