Open Access

Therapeutic role of histone deacetylase inhibition in an in vitro model of Graves' orbitopathy

  • Authors:
    • Hyeong Ju Byeon
    • Soo Hyun Choi
    • Don O. Kikkawa
    • Jaesang Ko
    • Jin Sook Yoon
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  • Published online on: September 26, 2024     https://doi.org/10.3892/mmr.2024.13342
  • Article Number: 218
  • Copyright: © Byeon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Graves' orbitopathy (GO), a manifestation of Graves' disease, is characterized by orbital fibroblast‑induced inflammation, leading to fibrosis or adipogenesis. Histone deacetylase (HDAC) serves a central role in autoimmune diseases and fibrosis. The present study investigated HDAC inhibition in orbital fibroblasts from patients with GO to evaluate its potential as a therapeutic agent. Primary cultured orbital fibroblasts were treated with an HDAC inhibitor, panobinostat, under the stimulation of IL‑1β, TGF‑β or adipogenic medium. Inflammatory cytokines, and fibrosis‑ and adipogenesis‑related proteins were analyzed using western blotting. The effects of panobinostat on HDAC mRNA expression were measured in GO orbital fibroblasts, and specific HDACs were inhibited using small interfering RNA transfection. Panobinostat significantly reduced the IL‑1β‑induced production of inflammatory cytokines and TGF‑β‑induced production of fibrosis‑related proteins. It also suppressed adipocyte differentiation and adipogenic transcription factor production. Furthermore, it significantly attenuated HDAC7 mRNA expression in GO orbital fibroblasts. In addition, the silencing of HDAC7 led to anti‑inflammatory and anti‑fibrotic effects. In conclusion, by inhibiting HDAC7 gene expression, panobinostat may suppress the production of inflammatory cytokines, profibrotic proteins and adipogenesis in GO orbital fibroblasts. The present in vitro study suggested that HDAC7 could be a potential therapeutic target for inhibiting the inflammatory, adipogenic and fibrotic mechanisms of GO.
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December-2024
Volume 30 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Byeon H, Choi S, Kikkawa DO, Ko J and Yoon J: Therapeutic role of histone deacetylase inhibition in an <em>in vitro</em> model of Graves' orbitopathy. Mol Med Rep 30: 218, 2024.
APA
Byeon, H., Choi, S., Kikkawa, D.O., Ko, J., & Yoon, J. (2024). Therapeutic role of histone deacetylase inhibition in an <em>in vitro</em> model of Graves' orbitopathy. Molecular Medicine Reports, 30, 218. https://doi.org/10.3892/mmr.2024.13342
MLA
Byeon, H., Choi, S., Kikkawa, D. O., Ko, J., Yoon, J."Therapeutic role of histone deacetylase inhibition in an <em>in vitro</em> model of Graves' orbitopathy". Molecular Medicine Reports 30.6 (2024): 218.
Chicago
Byeon, H., Choi, S., Kikkawa, D. O., Ko, J., Yoon, J."Therapeutic role of histone deacetylase inhibition in an <em>in vitro</em> model of Graves' orbitopathy". Molecular Medicine Reports 30, no. 6 (2024): 218. https://doi.org/10.3892/mmr.2024.13342