ArticleJournal of biomedical science2023
Endothelin-1 induces connective tissue growth factor expression in human lung fibroblasts by disrupting HDAC2/Sin3A/MeCP2 corepressor complex.
Article in Journal of biomedical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Characterization of the ctgf Promoter from Nibea coibor and its Response to TGF-β1 During Collagen Synthesis in Swim Bladder Cells.Marine biotechnology (New York, N.Y.) · 2026Article
- Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review).International journal of molecular medicine · 2026Review
- From allergens to epigenetics: how histone acetylation shapes immune gene expression in allergic diseases.Epigenomics · 2025Review
- Cirrhosis Promotes Cardiac Fibrosis Development by Inhibiting Notch1 in Cardiac Fibroblasts.JACC. Basic to translational science · 2025Article
- CTGF (CCN2): a multifaceted mediator in breast cancer progression and therapeutic targeting.Cancer metastasis reviews · 2025Review
- Identification of SIN3A as a Promising Epigenetic Target Against Allergic Rhinitis.Journal of inflammation research · 2025Article
- Endothelin-1 as a Candidate Biomarker of Systemic Sclerosis: A GRADE-Assessed Systematic Review and Meta-Analysis With Meta-Regression.Biomarker insights · 2025Article
- Involvement of HDAC2-mediated kcnq2/kcnq3 genes transcription repression activated by EREG/EGFR-ERK-Runx1 signaling in bone cancer pain.Cell communication and signaling : CCS · 2024Article
- Methyl-CpG-binding 2 K271 lactylation-mediated M2 macrophage polarization inhibits atherosclerosis.Theranostics · 2024Article
- Histone deacetylases: potential therapeutic targets for idiopathic pulmonary fibrosis.Frontiers in cell and developmental biology · 2024Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundReduction of histone deacetylase (HDAC) 2 expression and activity may contribute to amplified inflammation in patients with severe asthma. Connective tissue growth factor (CTGF) is a key mediator of airway fibrosis in severe asthma. However, the role of the HDAC2/Sin3A/methyl-CpG-binding protein (MeCP) 2 corepressor complex in the regulation of CTGF expression in lung fibroblasts remains unclear.
methodsThe role of the HDAC2/Sin3A/MeCP2 corepressor complex in endothelin (ET)-1-stimulated CTGF production in human lung fibroblasts (WI-38) was investigated. We also evaluated the expression of HDAC2, Sin3A and MeCP2 in the lung of ovalbumin-induced airway fibrosis model.
resultsHDAC2 suppressed ET-1-induced CTGF expression in WI-38 cells. ET-1 treatment reduced HDAC2 activity and increased H3 acetylation in a time-dependent manner. Furthermore, overexpression of HDAC2 inhibited ET-1-induced H3 acetylation. Inhibition of c-Jun N-terminal kinase, extracellular signal-regulated kinase, or p38 attenuated ET-1-induced H3 acetylation by suppressing HDAC2 phosphorylation and reducing HDAC2 activity. Overexpression of both Sin3A and MeCP2 attenuated ET-1-induced CTGF expression and H3 acetylation. ET-1 induced the disruption of the HDAC2/Sin3A/MeCP2 corepressor complex and then prompted the dissociation of HDAC2, Sin3A, and MeCP2 from the CTGF promoter region. Overexpression of HDAC2, Sin3A, or MeCP2 attenuated ET-1-stimulated AP-1-luciferase activity. Moreover, Sin3A- or MeCP2-suppressed ET-1-induced H3 acetylation and AP-1-luciferase activity were reversed by transfection of HDAC2 siRNA. In an ovalbumin-induced airway fibrosis model, the protein levels of HDAC2 and Sin3A were lower than in the control group; however, no significant difference in MeCP2 expression was observed. The ratio of phospho-HDAC2/HDAC2 and H3 acetylation in the lung tissue were higher in this model than in the control group. Overall, without stimulation, the HDAC2/Sin3A/MeCP2 corepressor complex inhibits CTGF expression by regulating H3 deacetylation in the CTGF promoter region in human lung fibroblasts. With ET-1 stimulation, the HDAC2/Sin3A/MeCP2 corepressor complex is disrupted and dissociated from the CTGF promoter region; this is followed by AP-1 activation and the eventual initiation of CTGF production.
conclusionsThe HDAC2/Sin3A/MeCP2 corepressor complex is an endogenous inhibitor of CTGF in lung fibroblasts. Additionally, HDAC2 and Sin3A may be of greater importance than MeCP2 in the pathogenesis of airway fibrosis.
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