hymecromone and Graves-Ophthalmopathy

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.. 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.. 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.. 4-MU represents a promising new therapeutic agent for GO based on its ability to inhibit hyaluronan production and adipogenesis, without decreasing cell viability.

Topics: Adipogenesis; Adult; Cell Proliferation; Cell Survival; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Graves Ophthalmopathy; Humans; Hyaluronan Synthases; Hyaluronic Acid; Hymecromone; Indicators and Reagents; Male; Middle Aged; Orbit; Real-Time Polymerase Chain Reaction