ArticleArthritis research & therapy2020
Long non-coding RNA HOTAIR induces GLI2 expression through Notch signalling in systemic sclerosis dermal fibroblasts.
Article in Arthritis research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 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
- Identification of diagnostic and therapeutic roles of programmed cell death-related proteins in dilated cardiomyopathy: a multi-omics and experimental validation study.Scientific reports · 2026Article
- Imbalance of Ciliary Programs Drives Fibroblast Differentiation and Fibrotic Signaling in Systemic Sclerosis.bioRxiv : the preprint server for biology · 2026Article
- 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
- 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
- Mutual Amplification of GLI2/Hedgehog and Transcription Factor JUN/AP-1 Signaling in Fibroblasts in Systemic Sclerosis: Potential Implications for Combined Therapies.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Emerging roles of non-coding RNAs in fibroblast to myofibroblast transition and fibrotic diseases.Frontiers in pharmacology · 2024Review
- Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders.International journal of molecular sciences · 2023Review
- lncHUB2: aggregated and inferred knowledge about human and mouse lncRNAs.Database : the journal of biological databases and curation · 2023Article
- Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis.International journal of molecular sciences · 2023Review
- Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.Frontiers in cell and developmental biology · 2023Review
- Novel role of long non-coding RNAs in autoimmune cutaneous disease.Journal of cell communication and signaling · 2022Review
- Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2022Review
- Genotype Triad forDiagnostics (Basel, Switzerland) · 2022Article
- Induction of Pro-Fibrotic CLIC4 in Dermal Fibroblasts by TGF-β/Wnt3a Is Mediated by GLI2 Upregulation.Cells · 2022Article
- The Roles of Noncoding RNAs in Systemic Sclerosis.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesSystemic sclerosis (SSc) is characterised by tissue fibrosis of the major organs of the body including the skin, lungs and heart. We have previously reported that the lncRNA HOTAIR plays a central role in the activation of SSc myofibroblasts, the key cellular elements of fibrosis. HOTAIR induces fibroblast activation through H3K27me3-mediated activation of the Notch signalling pathway. Here we aimed to identify the signalling events downstream of Notch that drive SSc myofibroblast activation.
methodsPatient fibroblasts were obtained from full-thickness forearm skin biopsies of 3 adult patients with SSc of recent onset. The lncRNA HOTAIR was expressed in healthy dermal fibroblasts by lentiviral transduction. Hedgehog signalling pathway was inhibited with GANT61 and GLI2 siRNA. Gamma secretase inhibitors RO4929097 and DAPT were used to block Notch signalling. GSK126 was used to inhibit Enhancer of Zeste 2 (EZH2).
resultsOverexpression of HOTAIR in dermal fibroblasts induced the expression of the Hedgehog pathway transcription factor GLI2. This is mediated by activation of Notch signalling following epigenetic downregulation of miRNA-34a expression. Inhibition of H3K27 methylation and Notch signalling reduced expression of GLI2 in HOTAIR-expressing fibroblasts as well as in SSc dermal fibroblasts. Importantly, the inhibition of GLI2 function using GANT61 or siRNA mitigates the pro-fibrotic phenotype induced by HOTAIR.
conclusionsOur data indicates that GLI2 expression is stably upregulated in SSc myofibroblasts through HOTAIR and that GLI2 mediates the expression of pro-fibrotic markers downstream of Notch.
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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.