รหัสดีโอไอ 10.14455/TSB.res.2019.55
Title The Effect of Histone Methyltransferase In Orbital Fibroblast From Graves' Ophthalmopathy
Creator Sita Virakul
Contributor 1. Sopita Visamol
2. Tanapat Palaga
3. Preamjit Saonanon
4. Vannakorn Pruksakorn
5. Willem A. Dik
Publisher The Thai Society for Biotechnology
Publication Year 2019
Keyword Fibrosis ,Graves' Ophthalmopathy ,Histone Methylation ,Orbital Fibroblast
Abstract Graves' ophthalmopathy (GO) is an extra-thyroidal complication of Graves' disease (GD). The clinical presentations of GO are upper eyelid retraction, erythema of periorbital tissue, conjunctivitis, proptosis and fibrosis. Some patients have severe symptoms such as optic neuritis leading to sightthreatening symptoms such as exposure keratitis and optic nerve compression or dysthyroid optic neuropathy. Platelet-derived growth factor-BB (PDGF-BB) is an important growth factor in the pathogenesis of GO. As orbital fibroblasts in orbital tissue express platelet-derived growth factor receptors (PDGF-R) on the surface, PDGF-BB stimulates orbital fibroblasts activities such as cytokine and hyaluronan production, proliferation and adipogenesis. Presently, active GO is treated with high-dose systemic glucocorticoids (GCs) as first line treatment which also carries several serious side effects, including hyperglycemia, fulminant hepatitis and a generalized state of immunosuppression. Therefore, novel therapeutic strategies with fewer complications are needed for GO. Epigenetic modifications control gene expression. One of the mechanisms is histone modification at the N-terminal amino acid. Histone methylation is the process of transferring methyl groups to lysine or arginine residues on the histone tail by a group of enzymes called histone methyltransferases (HMTs). In this study, we investigated the role of histone lysine methyltransferases ( KHMTs) and histone arginine methyltransferase ( PRMT5) in PDGF- BB- induced orbital fibroblasts activation by using specific inhibitors. Inhibition of KHMT (with DZNeP, BIX01294 or Pinometostat) as well as PRMT5 (with GSK591) inhibited PDGF-BBinduced hyaluronan production by orbital fibroblasts, both in a prophylactic and more treatment related experimental set-up. Inhibition of KHMT with DZNeP also prevented PDGF-BB-induced production of IL-6 and IL- 8 by orbital fibroblasts, while BIX01294 DNNeP, pinometostat and GSK591 also inhibited PDGF-BB-induced orbital fibroblasts proliferation, again both in a prophylactic and more treatment related experimental set-up. These data from inhibitors screening suggested that the KHMT enzymes (G9a, EZH2 and DOT1L) and PRMT5 induce orbital fibroblasts proliferation, cytokine and hyaluronan production.
Language EN
URL Website http://tsb2019.com/
Website title The 31st Annual Meeting of the Thai Society for Biotechnology and International Conference (TSB 2019)
ดิจิตอลไฟล์ Digital File

บรรณานุกรม

Sita Virakul และผู้แต่งคนอื่นๆ. (2019) The Effect of Histone Methyltransferase In Orbital Fibroblast From Graves' Ophthalmopathy. The Thai Society for Biotechnology:ม.ป.ท.
Sita Virakul และผู้แต่งคนอื่นๆ. 2019. The Effect of Histone Methyltransferase In Orbital Fibroblast From Graves' Ophthalmopathy. ม.ป.ท.:The Thai Society for Biotechnology;
Sita Virakul และผู้แต่งคนอื่นๆ. The Effect of Histone Methyltransferase In Orbital Fibroblast From Graves' Ophthalmopathy. ม.ป.ท.:The Thai Society for Biotechnology, 2019. Print.