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ELF3-induced miR-182 inhibits adipogenic differentiation in Graves' orbitopathy by targeting thyrotropin receptor
Sha Wang1,2,3, Lu Chen1,2,3, Bei Xu1,2,3
1Eye Center of Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China.
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.
Insights
MicroRNA-182 (miR-182) plays a role in Graves' orbitopathy (GO) pathogenesis by regulating adipogenesis. The ELF3/miR-182/TSHR pathway inhibits adipogenic differentiation, suggesting a therapeutic target for GO.
Area of Science:
- Endocrinology and Metabolism
- Molecular Biology
- Immunology
Background:
- Graves' orbitopathy (GO) is a common autoimmune disease with unclear pathogenesis.
- MicroRNAs (miRNAs) are implicated in autoimmune disease development.
- This study investigates the role of miR-182 in GO.
Purpose of the Study:
- To explore the diagnostic and functional role of miR-182 in Graves' orbitopathy.
- To elucidate the regulatory pathway involving ELF3, miR-182, and TSHR in adipogenesis.
- To assess the potential of targeting the ELF3/miR-182/TSHR axis for GO treatment.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for gene expression analysis.
- Enzyme-linked immunosorbent assay (ELISA) for triglyceride quantification.
- Oil Red O staining for lipid droplet assessment.
- Chromatin immunoprecipitation (ChIP), dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) to confirm molecular interactions.
Main Results:
- miR-182 expression was decreased, while TSHR and adipocytokines were upregulated in GO patients and in vitro models.
- miR-182 mimics inhibited adipogenesis, while miR-182 inhibitors promoted it.
- TSHR was identified as a direct target of miR-182, and ELF3 positively regulated miR-182 expression.
Conclusions:
- The ELF3/miR-182/TSHR axis plays a critical role in regulating adipogenic differentiation.
- This pathway alleviates Graves' orbitopathy by inhibiting adipogenesis.
- Targeting the ELF3/miR-182/TSHR axis presents a potential therapeutic strategy for GO.
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