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

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  • معلومة اضافية
    • المصدر:
      Publisher: D. A. Spandidos Country of Publication: Greece NLM ID: 101475259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-3004 (Electronic) Linking ISSN: 17912997 NLM ISO Abbreviation: Mol Med Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Athens, Greece : D. A. Spandidos
    • الموضوع:
    • نبذة مختصرة :
      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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    • Contributed Indexing:
      Keywords: Graves' orbitopathy; histone deacetylase 7; histone deacetylase inhibitor; orbital fibroblast; panobinostat
    • الرقم المعرف:
      0 (Histone Deacetylase Inhibitors)
      EC 3.5.1.98 (Histone Deacetylases)
      9647FM7Y3Z (Panobinostat)
      0 (Cytokines)
      EC 3.5.1.98 (HDAC7 protein, human)
      0 (Transforming Growth Factor beta)
      0 (Interleukin-1beta)
    • الموضوع:
      Date Created: 20240927 Date Completed: 20240927 Latest Revision: 20241012
    • الموضوع:
      20241012
    • الرقم المعرف:
      PMC11465418
    • الرقم المعرف:
      10.3892/mmr.2024.13342
    • الرقم المعرف:
      39329199