ArticleAnnals of the rheumatic diseases2020
Long non-coding RNA HOTAIR drives EZH2-dependent myofibroblast activation in systemic sclerosis through miRNA 34a-dependent activation of NOTCH.
Article in Annals of the rheumatic diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 93 citations in OpenAlex.
- Epigenetic pacemaker: A review of DNA methylation, histone lactylation, and non-coding RNAs in autoimmune skin diseases.Journal of translational autoimmunity · 2026Review
- Long Noncoding RNA H19 Mediates STAT3-Dependent Activation of Keratinocytes and Fibroblasts in Systemic Sclerosis Skin.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Histone modifications in skin fibrosis: linking immune dysregulation, metabolic reprogramming, and persistent fibrotic remodeling.Frontiers in immunology · 2026Review
- A State-of-the-Art Overview on (Epi)Genomics and Personalized Skin Rejuvenating Strategies.Pharmaceutics · 2025Review
- Systemic sclerosis, main culprits and involved signaling pathways.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- HOX and MEINOX in cellular plasticity, fibrosis, and cancer.World journal of stem cells · 2025Review
- Fibrotic Disease of the Skin and Lung: Shared Pathways, Environmental Drivers, and Therapeutic Opportunities in a Changing Climate.International journal of molecular sciences · 2025Review
- Natural products and long non-coding RNAs in prostate cancer: insights into etiology and treatment resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- LncRNA SYISL promotes fibroblast myofibroblast transition via miR-23a-mediated TRIOBP regulation.Cellular and molecular life sciences : CMLS · 2025Article
- Pathogenesis of systemic sclerosis: an integrative review of recent advances.Journal of rheumatic diseases · 2025Review
- Article
- Systemic Sclerosis Dermal Fibroblast Exosomes Trigger Type 1 Interferon Responses in Keratinocytes via a TBK/JAK/STAT Signaling Axis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- A review of recent studies on the pathogenesis of Systemic Sclerosis: focus on fibrosis pathways.Frontiers in immunology · 2025Review
- Biomarkers reflecting the pathogenesis, clinical manifestations, and guide therapeutic approach in systemic sclerosis: a narrative review.Clinical rheumatology · 2024Review
- Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- EZH2 as a major histone methyltransferase in PDGF-BB-activated orbital fibroblast in the pathogenesis of Graves' ophthalmopathy.Scientific reports · 2024Article
- Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead.Acta pharmaceutica Sinica. B · 2024Review
- miRNA-133 and lncRNA-H19 expressions and their relation to serum levels of PKM2 and TGF-β in patients with systemic sclerosis.Non-coding RNA research · 2024Article
- Emerging roles of non-coding RNAs in fibroblast to myofibroblast transition and fibrotic diseases.Frontiers in pharmacology · 2024Review
- Large-scale functional inference for skin-expressing lncRNAs using expression and sequence information.JCI insight · 2023Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundSystemic sclerosis (SSc) is characterised by autoimmune activation, tissue and vascular fibrosis in the skin and internal organs. Tissue fibrosis is driven by myofibroblasts, that are known to maintain their phenotype in vitro, which is associated with epigenetically driven trimethylation of lysine 27 of histone 3 (H3K27me3).
methodsFull-thickness skin biopsies were surgically obtained from the forearms of 12 adult patients with SSc of recent onset. Fibroblasts were isolated and cultured in monolayers and protein and RNA extracted. HOX transcript antisense RNA (HOTAIR) was expressed in healthy dermal fibroblasts by lentiviral induction employing a vector containing the specific sequence. Gamma secretase inhibitors were employed to block Notch signalling. Enhancer of zeste 2 (EZH2) was blocked with GSK126 inhibitor.
resultsSSc myofibroblasts in vitro and SSc skin biopsies in vivo display high levels of HOTAIR, a scaffold long non-coding RNA known to direct the histone methyltransferase EZH2 to induce H3K27me3 in specific target genes. Overexpression of HOTAIR in dermal fibroblasts induced EZH2-dependent increase in collagen and α-SMA expression in vitro, as well as repression of miRNA-34A expression and consequent NOTCH pathway activation. Consistent with these findings, we show that SSc dermal fibroblast display decreased levels of miRNA-34a in vitro. Further, EZH2 inhibition rescued miRNA-34a levels and mitigated the profibrotic phenotype of both SSc and HOTAIR overexpressing fibroblasts in vitro.
conclusionsOur data indicate that the EZH2-dependent epigenetic phenotype of myofibroblasts is driven by HOTAIR and is linked to miRNA-34a repression-dependent activation of NOTCH signalling.
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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.