ArticleThe Journal of investigative dermatology2013
p300 is elevated in systemic sclerosis and its expression is positively regulated by TGF-β: epigenetic feed-forward amplification of fibrosis.
Article in The Journal of investigative dermatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Histone modification of endothelial-mesenchymal transition in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Pooled it
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- Inhibition of β-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82.The Journal of investigative dermatology · 2017Trial
- An Update Comprehensive Review on Epigenetic Modifications and Therapies in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2026Review
- Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis.Nature reviews. Rheumatology · 2026Review
- Plant-Derived Agents and Systemic Sclerosis: A Systematic Review of Therapeutic Potential and Molecular Mechanisms.Current issues in molecular biology · 2026Review
- Histone modifications in skin fibrosis: linking immune dysregulation, metabolic reprogramming, and persistent fibrotic remodeling.Frontiers in immunology · 2026Review
- Emerging therapies for the treatment of systemic sclerosis.Nature reviews. Rheumatology · 2025Review
- Post-translational modifications of collagen and its related diseases in metabolic pathways.Acta pharmaceutica Sinica. B · 2025Review
- Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.Nature reviews. Molecular cell biology · 2024Review
- Lysine acetyltransferase 14 mediates TGF-β-induced fibrosis in ovarian endometrioma via co-operation with serum response factor.Journal of translational medicine · 2024Article
- Recent Insights into the Role of DNA Methylation and Histone Modifications in Systemic Sclerosis: A Scoping Review.Diagnostics (Basel, Switzerland) · 2024Article
- Expression of collagen-related piRNA is dysregulated in cultured dermal fibroblasts derived from patients with scleroderma.Intractable & rare diseases research · 2023Article
- Iguratimod attenuated fibrosis in systemic sclerosis via targeting early growth response 1 expression.Arthritis research & therapy · 2023Article
- EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.International journal of molecular sciences · 2023Review
- The deubiquitinase UCHL3 mediates p300-dependent chemokine signaling in alveolar type II cells to promote pulmonary fibrosis.Experimental & molecular medicine · 2023Article
- Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023Review
- Involvement of plasminogen activator inhibitor-1 in p300/p53-mediated age-related atrial fibrosis.PeerJ · 2023Article
- C/EBPβ enhances immunosuppression activity of myeloid-derived suppressor cells by a P300-mediated acetylation modification.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Fibrosis, the hallmark of systemic sclerosis (SSc), is characterized by persistent fibroblast activation triggered by transforming growth factor-β (TGF-β). As the acetyltransferase p300 has a key role in fibrosis and its availability governs the intensity of fibrotic responses, we investigated p300 expression in SSc and the molecular basis of its regulation. We found that expression of p300 was markedly elevated in SSc skin biopsies and was induced by TGF-β in explanted normal skin fibroblasts. Stimulation of p300 by TGF-β was independent of Smads and involved the early-immediate transcription factor Egr-1 (early growth response 1), a key regulator of profibrotic TGF-β signaling. Indeed, Egr-1 was both sufficient and necessary for p300 regulation in vitro and in vivo. Increased p300 accumulation in TGF-β-treated fibroblasts was associated with histone hyperacetylation, whereas p300 depletion, or selective pharmacological blockade of its acetyltransferase activity, attenuated TGF-β-induced responses. Moreover, TGF-β enhanced both p300 recruitment and in vivo histone H4 acetylation at the COL1A2 (collagen, type I, α2) locus. These findings implicate p300-mediated histone acetylation as a fundamental epigenetic mechanism in fibrogenesis and place Egr-1 upstream in TGF-β-driven stimulation of p300 gene expression. The results establish a firm link between fibrosis with aberrant p300 expression and epigenetic activity that, to our knowledge, is previously unreported. Targeted disruption of p300-mediated histone acetylation might therefore represent a viable antifibrotic strategy.
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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.