Biglycan knockdown improves Graves' orbitopathy (GO)-like features via inhibiting NF-kB and ERK signaling

Graves' orbitopathy (GO) is an autoimmune disease characterized by orbital inflammation, fibroblast activation, and adipogenesis, with limited effective therapies. This study aimed to investigate the role of biglycan (BGN) in GO pathogenesis and its underlying mechanisms.

Bioinformatic analyses were performed to identify differentially expressed genes in GO tissues. BGN protein levels were validated in orbital adipose tissues from GO patients. Functional effects of BGN were examined by overexpression or knockdown in human GO orbital fibroblasts (GO-OFs) in vitro. In vivo, a thyroid-associated ophthalmopathy (TAO) mouse model was used to evaluate the effects of Bgn knockdown on orbital fibrosis and adipogenesis.

BGN expression was significantly upregulated in GO orbital tissues. In vitro, BGN overexpression promoted, while BGN knockdown attenuated, fibrosis and adipogenesis in GO-OFs. Mechanistically, BGN activated nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK) signaling pathways. In vivo, Bgn knockdown reduced GO-like pathological features, including fibrosis and adipose expansion, and decreased NF‑κB and ERK signaling activation.

BGN contributes to fibrosis and adipogenesis in GO via NF‑κB and ERK signaling activation. These findings elucidate a pivotal role for BGN in GO pathogenesis and highlight its potential as a therapeutic target for GO treatment.