Published in:
01-05-2020 | Oculoplastics and Orbit
4-Methylumbelliferone suppresses hyaluronan and adipogenesis in primary cultured orbital fibroblasts from Graves’ orbitopathy
Authors:
Yeonjung Yoon, Min Kyung Chae, Eun Jig Lee, Jin Sook Yoon
Published in:
Graefe's Archive for Clinical and Experimental Ophthalmology
|
Issue 5/2020
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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.