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

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33 Citations (Scopus)


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 of Sma 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.

Original languageEnglish
Pages (from-to)407-414
Number of pages8
JournalBritish Journal of Ophthalmology
Issue number3
Publication statusPublished - 2018 Mar

Bibliographical note

Funding Information:
Funding This study was supported by a faculty research grant from Yonsei University, College of Medicine (grant no. 6-2015-0046 to JSY) and by the National Research Foundation of Korea (NRF-2017R1A1A1A05001051).

Publisher Copyright:
© 2018 Article author(s). All rights reserved.

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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