ELF3-induced miR-182 inhibits adipogenic differentiation in Graves’ orbitopathy by targeting thyrotropin receptor

INTRODUCTION: Graves’ orbitopathy (GO) is a common autoimmune disease, but its specific pathogenesis has not been fully elucidated. MicroRNAs (miRNAs) possess an important regulatory function in the occurrence and development of autoimmune diseases. In the present study, we explored the potential role of miR-182 in the diagnosis of GO. MATERIAL AND METHODS: The expression of miR-182, thyrotropin receptor (TSHR) and adipocytokines was ascertained by qRT-PCR assay. The triglyceride (TG) content was ascertained by ELISA assay. The lipid droplet content was identified by Oil Red O staining. The relationship between E74-like factor 3 (ELF3), miR-182 and TSHR was confirmed by ChIP, dual-luciferase reporter assay and RIP. RESULTS: The expression of miR-182 decreased, while TSHR increased, and adipocytokine (adiponectin, leptin, PPAR-γ, and AP2) levels were upregulated in preorbital adipose tissue of patients with GO and differential medium induced (DM-induced) 3T3-L1 cells. MiR-182 mimics inhibited adipocytokine expression, TG content and lipid droplets; however, miR-182 inhibitor had the opposite results. TSHR was a target gene of miR-182, and TSHR overexpression (oe-TSHR) reversed the effect of miR-182 mimics on adipogenic differentiation of 3T3-L1 by DM treatment. ELF3 transcription promoted miR-182 expression. Oe-ELF3 inhibited adipocytokine expression and reduced TG content and lipid droplets in DM-induced 3T3-L1 cells. MiR-182 inhibitor reversed the effect of oe-ELF3 on adipogenic differentiation in 3T3-L1. CONCLUSIONS: ELF3/miR-182/TSHR axis alleviated Graves’ orbitopathy by inhibiting adipogenic differentiation.