Epigenetic Modulation of Thyroid-Stimulating Hormone Receptor Expression in Orbital Fibroblasts From Graves' Ophthalmopathy: Target for Treatment.

Authors

Rajit Chompoowong, Pimchanok Phankeaw, Apinya Suwannavong, Sopita Visamol, Sukonlaphat Pitikiadtikun, Preamjit Saonanon, Vannakorn Pruksakorn, Panida Potita, Tanapat Palaga, Sita Virakul

Published in

Investigative ophthalmology & visual science. Volume 67. Issue 10. Pages 21. Aug 03, 2026.

Abstract

This study aims to investigate the expression and function of DNA methyltransferases (DNMTs) and histone methyltransferase EZH2 in regulating the expression of thyroid-stimulating hormone receptor (TSHR) and fibrotic markers by orbital fibroblasts from Graves' ophthalmopathy (GO) patients.
DNMTs mRNA levels were measured in orbital fibroblasts from healthy controls (control orbital fibroblasts), active GO fibroblasts, and inactive GO fibroblasts (iGOFs). TSHR and other fibrotic markers were measured in iGOFs treated with platelet-derived growth factor (PDGF)-BB and decitabine (a DNMT inhibitor) or DZNep (an EZH2 inhibitor) or small interfering RNA by RT-qPCR or Western blotting.
DNMT1 and DNMT3A mRNA expressions were significantly higher in active GOFs compared with iGOFs and control orbital fibroblasts. Among all DNMTs, DNMT1 expression was at the highest levels. Upon PDGF-BB stimulation, DNMT1 and DNMT3A mRNA levels in iGOFs were significantly induced. Decitabine significantly inhibited PDGF-BB-induced cell viability and TSHR mRNA levels in iGOFs, whereas DNMT1 silencing partly reduced TSHR protein. Because a positive correlation between DNMT1 and EZH2 expression in iGOF was observed, the regulatory role of EZH2 on TSHR expression was also investigated. DZNep slightly decreased TSHR mRNA expression in iGOFs and iGO orbital tissue, whereas EZH2 silencing partly affects TSHR expression.
This study demonstrates that DNMT1 is the major DNMT during the active stage of GO. Moreover, DNMT1 is inducible upon PDGF-BB stimulation in iGOFs, suggesting an important role of PDGF-BB and DNMT1 during an active stage of GO. Our findings also highlighted that the inhibition of DNMT or EZH2 potentially suppressed TSHR mRNA expression, suggesting potential therapies targeting DNMT/EZH2 in controlling GO progression.

PMID:
42565655
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.