MiR-130a-3p plays a key role in adipocyte differentiation of orbital fibroblasts (OFs) in Graves' ophthalmopathy by regulating the Wnt/β-catenin signaling pathway

Abstract

Abstract Objective To study the effects of miR-130a-3p on the adipocyte differentiation of orbital fibroblasts in Graves’ ophthalmopathy (GO). Methods The expression level of key transcription factors in the Wnt/β-catenin signaling pathway and adipocytes were detected in the human primary orbital fibroblasts (OFs) obtained from GO, non-GO patients or OFs (GO) treated with LiCl (Wnt/beta-catenin pathway activator). The content of IL-1β, TNF-α and IFN-γ and the expression level of ICAM-1, COX-2, and MCP-1 were detected in OFs (GO) or OFs (GO) treated with LiCl. The effects of miR-130a-3p mimics on the differentiation of orbital fibroblasts and the potential mechanisms were investigated. Results The ratio between the expression level of p-GKS-3β、GKS-3β and β-catenin was decreased significantly, the PPAR-γ and C/EBPα were increased significantly in OFs (GO). After the treatment of LiCl in OFs (GO), the ratio between the expression level of p-GKS-3β、GKS-3β and β-catenin were increased, while PPAR-γ and C/EBPα were decreased. Cell viability, the number of adipocytes, IL-1β, TNF-α, IFN-γ, ICAM, COX-2, and MCP-1were decreased significantly in OFs (GO) treated with LiCl. The expression of related proteins was reversed after OFs (GO) treated with miR-130a-3p mimics, the alterations induced by miR-130a-3p mimics were reversed by pcDNA- PPAR-γ. Conclusions In the present study, miR-130a-3p inhibited adipocyte differentiation in OFs from patients with GO. The underlying mechanism might be the negative regulation of PPARγ-mediated adipogenesis via the Wnt/β-catenin signaling pathway by miR-130a-3p. MiR-130a-3p might be an useful target in treating Graves' ophthalmopathy.