ArticleProceedings of the National Academy of Sciences of the United States of America2019
Inhibition of EZH2 prevents fibrosis and restores normal angiogenesis in scleroderma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 105 citations in OpenAlex.
- MEF2A nuclear translocation mediated by ROCK phosphorylation promotes EZH2 expression and peritoneal fibrosis.Renal failure · 2026Article
- Gain of function NOTCH4 variants disrupt angiogenesis in systemic sclerosis.Annals of the rheumatic diseases · 2026Article
- A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model.JCI insight · 2026Article
- SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic Therapies for Inflammatory and Immune-Mediated Skin Diseases.Biomedicines · 2026Review
- Histone modifications in skin fibrosis: linking immune dysregulation, metabolic reprogramming, and persistent fibrotic remodeling.Frontiers in immunology · 2026Review
- Article
- Fibrotic Disease of the Skin and Lung: Shared Pathways, Environmental Drivers, and Therapeutic Opportunities in a Changing Climate.International journal of molecular sciences · 2025Review
- Post-translational modifications of collagen and its related diseases in metabolic pathways.Acta pharmaceutica Sinica. B · 2025Review
- Article
- Targeting CD13/Aminopeptidase N as a Novel Therapeutic Approach for Scleroderma Fibrosis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Epigenetic Regulation in Myocardial Fibroblasts and Its Impact on Cardiovascular Diseases.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway.Diabetes & metabolism journal · 2024Article
- EZH2 as a major histone methyltransferase in PDGF-BB-activated orbital fibroblast in the pathogenesis of Graves' ophthalmopathy.Scientific reports · 2024Article
- O-GlcNAc regulates anti-fibrotic genes in lung fibroblasts through EZH2.Journal of cellular and molecular medicine · 2024Article
- Recent Insights into the Role of DNA Methylation and Histone Modifications in Systemic Sclerosis: A Scoping Review.Diagnostics (Basel, Switzerland) · 2024Article
- Systems-based identification of the Hippo pathway for promoting fibrotic mesenchymal differentiation in systemic sclerosis.Nature communications · 2024Article
- The roles of EZH2 in cancer and its inhibitors.Medical oncology (Northwood, London, England) · 2023Review
- Variation in DNA Methylation in Avian Nestlings Is Largely Determined by Genetic Effects.Molecular biology and evolution · 2023Article
- SMYD3 regulates gastric cancer progression and macrophage polarization through EZH2 methylation.Cancer gene therapy · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Scleroderma (SSc) is a complex disease that involves activation of the immune system, vascular complications, and tissue fibrosis. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) mediates trimethylation of lysine 27 of histone 3 (H3K27me3), which acts as a repressive epigenetic mark. Both EZH2 and H3K27me3 were elevated in SSc dermal fibroblasts and endothelial cells compared with healthy controls. EZH2 inhibitor DZNep halted fibrosis both in vitro and in vivo. In SSc fibroblasts, DZNep dose-dependently reduced the expression of profibrotic genes and inhibited migratory activity of SSc fibroblasts. We show that epigenetic dysregulation and overexpression of LRRC16A explains EZH2-mediated fibroblast migration in SSc. In endothelial cells, inhibition of EZH2 restored normal angiogenesis in SSc via activating the Notch pathway, specifically by up-regulating the Notch ligand DLL4. Our results demonstrate that overexpression of EZH2 in SSc fibroblasts and endothelial cells is profibrotic and antiangiogenic. Targeting EZH2 or EZH2-regulated genes might be of therapeutic potential in SSc.
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Registered trials
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 OpenQuestion graph.