miR-96-5p Induces Orbital Fibroblasts Differentiation by Targeting Smad7 and Promotes the Development of Thyroid-Associated Ophthalmopathy

BACKGROUND: Recent evidence shows that adipogenic differentiation of orbital fibroblasts (OFs) promotes the development of thyroid-associated ophthalmopathy (TAO), an organ-specific immune disease. Furthermore, miR-96-5p has been linked to adipogenic differentiation of C2C12 myoblasts and is significantly correlated with the severity of TAO. The purpose of this study is to look into the role of miR-96-5p in the adipogenesis of OFs with TAO. METHODS: The orbital tissues from TAO patients and non-TAO participants were collected, and primary OFs were isolated and cultured for further analysis. miR-96-5p expression was examined using qRT-PCR. The adipogenic differentiation of OFs was then studied. RESULTS: Orbital fibroblasts isolated from adipose tissues of TAO patients (t-OFs) demonstrated greater adipogenic differentiation ability than OFs isolated from adipose tissues of non-TAO participants. miR-96-5p was found to be overexpressed in the orbital tissues of TAO patients and t-OFs. Further research revealed that miR-96-5p, by targeting Smad7, could exacerbate PPAR-γ/C/EBPα signaling-induced adipogenic differentiation of t-OFs. However, inhibiting miR-96-5p could block t-OFs adipogenic differentiation-mediated adipogenesis via Smad7/PPAR-γ/C/EBPα. CONCLUSIONS: miR-96-5p plays a critical regulatory role in the development of TAO by targeting Smad7 and promoting adipogenic differentiation of OFs.