Evidence map›Paper›PMID 38575707›Full record

ArticleScientific reports2024

EZH2 as a major histone methyltransferase in PDGF-BB-activated orbital fibroblast in the pathogenesis of Graves' ophthalmopathy.

Sopita Visamol, Tanapat Palaga, Preamjit Saonanon, Vannakorn Pruksakorn, Nattiya Hirankarn, P Martin van Hagen, Willem A Dik, Sita Virakul

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Sopita VisamolMedical Microbiology, Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.ORCID 0000-0002-6527-8543
Tanapat PalagaDepartment of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
Preamjit SaonanonDepartment of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Vannakorn PruksakornDepartment of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Nattiya HirankarnDepartment of Microbiology, Faculty of Medicine, Center of Excellence in Immunology and Immune Mediated Disease, Chulalongkorn University, Bangkok, Thailand.
P Martin van HagenDepartment of Microbiology, Faculty of Medicine, Center of Excellence in Immunology and Immune Mediated Disease, Chulalongkorn University, Bangkok, Thailand.
Willem A DikLaboratory Medical Immunology, Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Sita VirakulDepartment of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand. sita.v@chula.ac.th.ORCID 0000-0003-2509-6793
Chulalongkorn University · THErasmus MC · NL

Funding

Thailand Science Research and Innovation Fund Chulalongkorn University HEA662300075The National Research Council of Thailand 811/2563The NSRF via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation B16F640117The Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation (OPS MHESI), Thailand Science Research and Innovation (TSRI) RGNS 64-019
6 · The paper itself

Abstract

Graves' ophthalmopathy (GO) is an extra-thyroidal complication of Graves' disease which can lead to vision loss in severe cases. Currently, treatments of GO are not sufficiently effective, so novel therapeutic strategies are needed. As platelet-derived growth factor (PDGF)-BB induces several effector mechanisms in GO orbital fibroblasts including cytokine production and myofibroblast activation, this study aims to investigate the roles of histone lysine methyltransferases (HKMTs) in PDGF-BB-activated GO orbital fibroblasts by screening with HKMTs inhibitors library. From the total of twelve selective HKMT inhibitors in the library, EZH2, G9a and DOT1L inhibitors, DZNeP, BIX01294 and Pinometostat, respectively, prevented PDGF-BB-induced proliferation and hyaluronan production by GO orbital fibroblasts. However, only EZH2 inhibitor, DZNeP, significantly blocked pro-inflammatory cytokine production. For the HKMTs expression in GO orbital fibroblasts, PDGF-BB significantly and time-dependently induced EZH2, G9a and DOT1L mRNA expression. To confirm the role of EZH2 in PDGF-BB-induced orbital fibroblast activation, EZH2 silencing experiments revealed suppression of PDGF-BB-induced collagen type I and α-SMA expression along with decreasing histone H3 lysine 27 trimethylation (H3K27me3) level. In a more clinically relevant model than orbital fibroblast culture experiments, DZNeP treated GO orbital tissues significantly reduced pro-inflammatory cytokine production while slightly reduced ACTA2 mRNA expression. Our data is the first to demonstrate that among all HKMTs EZH2 dominantly involved in the expression of myofibroblast markers in PDGF-BB-activated orbital fibroblast from GO presumably via H3K27me3. Thus, EZH2 may represent a novel therapeutics target for GO.

Indexed as

Graves OphthalmopathyHistonesBecaplerminCells, CulturedCytokinesEnhancer of Zeste Homolog 2 ProteinFibroblastsHistone MethyltransferasesHumansLysineOrbitProto-Oncogene Proteins c-sisRNA, MessengerBecaplerminCytokinesEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistone MethyltransferasesHistonesLysineProto-Oncogene Proteins c-sisRNA, MessengerEZH2Graves’ ophthalmopathyH3K27me3Histone lysine methyltransferasesOrbital fibroblast

Identifiers

PMID38575707
PMCPMC10994939
OpenAlexW4393932826

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.