PT  - JOURNAL ARTICLE
AU  - Sun Young Jang
AU  - Seong Jun Park
AU  - Min Kyung Chae
AU  - Joon H Lee
AU  - Eun Jig Lee
AU  - Jin Sook Yoon
TI  - Role of microRNA-146a in regulation of fibrosis in orbital fibroblasts from patients with Graves’ orbitopathy
AID  - 10.1136/bjophthalmol-2017-310723
DP  - 2018 Mar 01
TA  - British Journal of Ophthalmology
PG  - 407--414
VI  - 102
IP  - 3
4099  - http://bjo.bmj.com/content/102/3/407.short
4100  - http://bjo.bmj.com/content/102/3/407.full
SO  - Br J Ophthalmol2018 Mar 01; 102
AB  - Aim To examine the role of microRNA-146a (miR-146a) in the regulation of fibrosis in an in vitro model of Graves’ orbitopathy (GO).Methods Orbital fat/connective tissues were harvested from patients with GO and non-GO for primary orbital fibroblast cultures. The effects of transforming growth factor-β (TGF-β), a potent cytokine that promotes fibrosis, on miR-146a expression were analysed in GO and non-GO orbital fibroblasts using quantitative real-time PCR. The effects of overexpressed miR-146a on TGF-β-induced fibrotic markers were examined in GO orbital fibroblasts by western blot analysis. Expression ofSma and Mad related family (Smad) 4/tumour necrosis factor receptor-associated factor 6 (TRAF6) after transfection of miR-146a mimics or inhibitors were examined.Results TGF-β induced an increase in miR-146a expression in orbital fibroblasts from patients with GO in a time-dependent and concentration-dependent manner. miR-146a mimics further decreased the production of TGF-β-induced fibronectin, collagen Iα and α-smooth muscle actin protein. The Smad4 and TRAF6 protein levels were significantly decreased by miR-146a mimics, compared with control mimics, and significantly increased on inhibition of miR-146a production compared with a control.Conclusions miR-146a plays a role as a negative regulator in the production of TGF-β-induced fibrotic markers. Thus, miR-146a may be involved in the regulation of fibrosis in orbital fibroblasts from patients with GO.