circ-0007006 attenuates fibrosis in thyroid-associated ophthalmopathy by stabilizing HBEGF expression in vitro

Abstract

Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disease characterized by inflammation and tissue remodeling, with fibrosis being a predominant and often irreversible feature in type II TAO. While immunosuppressive therapies offer limited efficacy, there remains a critical need to identify effective molecular targets for fibrotic TAO. Circular RNAs (circRNAs) have emerged as key regulators in various diseases, yet their roles in TAO are largely unexplored. In this study, we identified hsa_circ_0007006 as significantly downregulated in fibrotic TAO tissues through high-throughput RNA sequencing. Functional assays in orbital fibroblasts revealed that circ-0007006 suppresses fibrosis by downregulating COL1A1, α-SMA, HAS1, and HAS2, and inhibiting SMAD2/3 phosphorylation. Mechanistically, circ-0007006 functions as a competing endogenous RNA for miR-383-3p, thereby stabilizing HBEGF expression. Rescue experiments showed that exogenous HBEGF alleviates the pro-fibrotic effects induced by circ-0007006 knockdown. These findings identify the circ-0007006/miR-383-3p/HBEGF axis as a novel regulatory pathway in TAO fibrosis and support circ-0007006 as a potential therapeutic target for the fibrotic subtype of TAO.