MicroRNA-27 inhibits adipogenic differentiation in orbital fibroblasts from patients with Graves' orbitopathy.

Sun Young Jang,Joon H Lee,Jin Sook Yoon,Eun Jig Lee,Min Kyung Chae,Jeffrey Alan Deiuliis

doi:10.1371/journal.pone.0221077

Abstract

BackgroundTo investigate the role of microRNA (miR)-27a and miR-27b in adipogenesis in an in vitro model of Graves’ orbitopathy (GO).MethodsOrbital fat tissues were harvested from GO and non-GO participants for primary orbital fibroblast cultures. The expression levels of miR-27a and miR-27b between GO and non-GO orbital fat tissues were compared. During adipogenesis of GO orbital fibroblasts, the expression levels of miR-27a and miR-27b were determined, and the effects of mimics of miR-27a and miR-27b transfection on adipogenesis of GO orbital fibroblast were investigated.ResultsReal time-polymerase chain reaction showed significantly more decreases in miR-27a and miR-27b levels in orbital fat tissues in GO participants than in non-GO participants (p < 0.05). The expression of both miR-27a and miR-27b was highest in orbital fibroblasts at day 0 and declined gradually after the induction of adipogenic differentiation. The expression levels of PPARγ, CCAAT/enhancer binding protein (C/EBP)α and C/EBPβ were decreased and Oil Red O-stained lipid droplets were lower in GO orbital fibroblasts transfected with miR-27a and miR-27b mimics than in negative controls.ConclusionsOur results indicated that miR-27a and miR-27b inhibited adipogenesis in orbital fibroblasts from GO patients. Further studies are required to examine the potential of miR-27a and miR-27b as targets for therapeutic strategies.

Highlights

Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit [1,2,3]
The expression levels of peroxisome-proliferator activated receptor-γ (PPARγ), CCAAT/enhancer binding protein (C/EBP)α and C/EBPβ were decreased and Oil Red O-stained lipid droplets were lower in GO orbital fibroblasts transfected with miR-27a and miR-27b mimics than in negative controls
Our results indicated that miR-27a and miR-27b inhibited adipogenesis in orbital fibroblasts from GO patients

Summary

Introduction

Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit [1,2,3]. Patients with GO often suffer more from a disfiguring appearance than from their general condition due to Graves’ disease. Adipogenesis, the transition of activated orbital fibroblasts into adipocytes, can lead to orbital proptosis in GO patients [6]. Proptosis, which is a leading cause of a disfiguring appearance, is usually treated with orbital decompression [7,8,9]. Even though orbital decompression is a well-established procedure for treating proptosis, the risks of postoperative complications such as infection, bleeding, surgically-induced diplopia, or insufficient proptosis reduction still exist [10,11,12]. To investigate the role of microRNA (miR)-27a and miR-27b in adipogenesis in an in vitro model of Graves’ orbitopathy (GO)

Methods

Results

Conclusion