4-Methylumbelliferone suppresses hyaluronan and adipogenesis in primary cultured orbital fibroblasts from Graves’ orbitopathy

Yeonjung Yoon, Min Kyung Chae, Eun Jig Lee, Jin Sook Yoon

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: In Graves’ orbitopathy (GO), hyaluronan secreted by orbital fibroblasts contributes to orbital tissue expansion. The goal of this research was to evaluate the potential benefit of 4-methylumbelliferone (4-MU), a hyaluronan synthase (HAS) inhibitor, in primary cultured orbital fibroblasts from Graves’ orbitopathy. Methods: We assessed the viability of orbital fibroblasts using a live/dead cell assay. Hyaluronan synthesis was evaluated by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qPCR). Adipogenesis was assessed by Oil Red O staining and qPCR of adipogenic transcription factors. Results: In orbital fibroblasts treated with 4-MU (up to 1000 μM), cell viability was preserved by 90%. 4-MU significantly inhibited HAS gene expression and hyaluronan production (*P < 0.05). With respect to adipogenesis, 4-MU suppressed the accumulation of lipids and reduced the number of adipocytes, while decreasing expression of adipogenic transcription factors. Conclusions: 4-MU represents a promising new therapeutic agent for GO based on its ability to inhibit hyaluronan production and adipogenesis, without decreasing cell viability.

Original languageEnglish
Pages (from-to)1095-1102
Number of pages8
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume258
Issue number5
DOIs
Publication statusPublished - 2020 May 1

Bibliographical note

Funding Information:
This study was funded by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2016M3A9E9941746).

Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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