The Role of Fibrogenesis and Extracellular Matrix Proteins in the Pathogenesis of Graves’ Ophthalmopathy

Abstract

Graves’ ophthalmopathy (GO), or thyroid eye disease (TED), is the most frequent extrathyroidal manifestation of Graves’ disease (GD). Inflammation and subsequent aberrant tissue remodeling with fibrosis are important pathogenesis. There are many proposed mechanisms and molecular pathways contributing to tissue remodeling and fibrosis in GO, including adipogenesis, fibroblast proliferation and myofibroblasts differentiation, oxidative stress, endoplasmic reticulum (ER) stress, hyaluronan (HA) and glycosaminoglycans (GAGs) accumulation in the extracellular matrix (ECM) and new concepts of epigenetics modification, such as histone modification, DNA methylation, non-coding RNAs, and gut microbiome. This review summarizes the current understanding of ECM proteins and associated tissue remodeling in the pathogenesis and potential mediators for the treatment of GO.

Keywords

• Graves’ orbital fibroblasts
• Graves’ ophthalmopathy (GO)
• transforming growth factor-β1 (TGF-β1)
• oxidative stress
• endoplasmic reticulum (ER)
• epigenetics