MiRNA-21 promotes fibrosis in orbital fibroblasts from thyroid-associated ophthalmopathy

PURPOSE: This study aimed to determine the role of miR-21 in orbital fibroblasts obtained from donors with thyroid-associated ophthalmopathy (TAO) and to elucidate the regulation of fibrosis by miR-21 in the pathological process of TAO. METHODS: The expression of miR-21 was investigated in orbital tissues from 26 donors with TAO and 10 donors without TAO. Human orbital fibroblasts were cultivated from TAO donors, and the role of miR-21 in orbital fibroblast proliferation, apoptosis, and differentiation was analyzed. Moreover, the effect of transforming growth factor-beta1 (TGF-β1) on miR-21 expression was also analyzed. In addition, the regulation of miR-21 in TGF-β1-induced collagen production was determined. RESULTS: The expression of miR-21 in orbital fibroblasts from TAO was higher than in donors without TAO. Additional experiments demonstrated that miR-21 enhanced proliferation, decreased apoptosis, and promoted differentiation in TAO orbital fibroblasts. Moreover, this study also showed that TGF-β1 induced miR-21 expression in a time- and dose-dependent manner and miR-21 promoted collagen I mRNA expression and total collagen production induced by TGF-β1. Additionally, miR-21 activated the TGF-β1/Smad signaling pathway by enhancing Smad3 phosphorylation. CONCLUSIONS: The present study shows that miR-21 regulates cell proliferation, apoptosis, and differentiation in orbital fibroblasts from TAO, and acts as a mediator in TGF-β1-induced collagen production. These data predict a close association between miR-21 and orbital muscle fibrosis, and provide a novel therapeutic target for TAO.