PURPOSE

Thyroid eye disease (TED) is an autoimmune condition of the orbit characterized by significant morbidity. MicroRNAs (miRNAs) have been identified as key modulators of immune responses and fibrotic processes, with miR-320a emerging as a potential modulator in TED pathogenesis.

METHODS

This study investigated miR-320a's role in TED by analyzing its expression in TED tissues and assessing the impact of its inhibition on fibroblast activation, fibrosis, and oxidative stress. Peroxiredoxin 3 (PRDX3) was identified as a direct target of miR-320a, and its functional consequences were evaluated. In vivo experiments were also conducted to validate the findings.

RESULTS

Inhibition of miR-320a reduced fibroblast activation, fibrosis, and oxidative stress markers. PRDX3 knockdown amplified these effects, indicating its importance in miR-320a-mediated pathways. Overexpression of miR-320a further promoted fibroblast activation, as evidenced by decreased cell viability, DNA synthesis, and the expression levels of fibrotic markers. PRDX3 overexpression could also notably eliminate the effects of miR-320a overexpression. In vivo targeting of the miR-320a/PRDX3 axis reduced oxidative stress and fibrosis in TED models.

CONCLUSIONS

The study highlights the critical role of miR-320a in TED pathogenesis through its regulation of orbital fibroblast (OF) activation, fibrosis, oxidative stress, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, mediated by its interaction with PRDX3. Targeting the miR-320a/PRDX3 axis represents a promising therapeutic strategy to alleviate the oxidative stress and fibrotic alterations in TED, underscoring the potential of miR-320a as a therapeutic target in managing TED progression.