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Role of microRNA-146a in regulation of fibrosis in orbital fibroblasts from patients with Graves' orbitopathy

 Sun Young Jang  ;  Seong Jun Park  ;  Min Kyung Chae  ;  Joon H Lee  ;  Eun Jig Lee  ;  Jin Sook Yoon 
 British Journal of Ophthalmology, Vol.102(3) : 407-414, 2018 
Journal Title
 British Journal of Ophthalmology 
Issue Date
experimental laboratory
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-beta (TGF-beta), 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-beta-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-beta 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-beta-induced fibronectin, collagen Ialpha and alpha-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-beta-induced fibrotic markers. Thus, miR-146a may be involved in the regulation of fibrosis in orbital fibroblasts from patients with GO.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Jin Sook(윤진숙) ORCID logo https://orcid.org/0000-0002-8751-9467
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
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