ArticleJCI insight2019
CBX5/G9a/H3K9me-mediated gene repression is essential to fibroblast activation during lung fibrosis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
57 citing papers in PubMed, 89 citations in OpenAlex.
- RUNX1 is a mediator of fibrotic activation and epigenetic memory in lung fibroblasts.American journal of respiratory cell and molecular biology · 2026Article
- A Circuit of Mechanically Regulated Transcription Factors Balances Regenerative and Fibrotic Memory of Mesenchymal Stromal Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From force to fate: Implications of mechanomemory in lung disease.Respiratory research · 2026Review
- ECM-Stiffness Mediated Persistent Fibroblast Activation Requires Integrin and Formin Dependent Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Stretch strain shifts optic nerve head astrocyte metabolism to enrich α-ketoglutarate and the pentose phosphate pathway.Scientific reports · 2026Article
- Idiopathic pulmonary fibrosis from a multiscale mechanobiology perspective: Mechanisms and future therapeutic prospects.iScience · 2026Review
- New Clues to the Challenge of Knee Arthrofibrosis: From Molecules to Therapies.The Journal of the American Academy of Orthopaedic Surgeons · 2026Review
- Review
- Fibroblast mechanoperception instructs pulmonary developmental and pattern specification gene expression programs.PLoS genetics · 2025Article
- Mechanotransduction-Epigenetic Coupling in Pulmonary Regeneration: Multifunctional Bioscaffolds as Emerging Tools.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Exploring the Influence of Metabolic Changes in Fibrotic Lung Diseases.Pulmonary circulation · 2025Review
- Matrix Stiffness Regulates TGFβ1-Induced αSMA Expression via a G9a-LATS-YAP Signaling Cascade.FASEB bioAdvances · 2025Article
- Emerging mechanomedicines informed by mechanotransduction along the integrin-cytoskeleton-nucleus axis.APL bioengineering · 2025Review
- The Sound of Silence: Suppressing CBX5 Decreases Fibrosis by Inhibiting Fibroblasts.American journal of respiratory cell and molecular biology · 2025Article
- Targeting the Epigenetic Regulator CBX5 Promotes Fibroblast Metabolic Reprogramming and Inhibits Lung Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- Post-translational modifications of collagen and its related diseases in metabolic pathways.Acta pharmaceutica Sinica. B · 2025Review
- Mechanomemory of pulmonary fibroblasts demonstrates reversibility of transcriptomics and contraction phenotypes.Biomaterials · 2025Article
- Inhibition of RUNX1 slows the progression of pulmonary hypertension by targeting CBX5.Biomolecules & biomedicine · 2025Article
- An Overview of the Role of Genetic factors in Idiopathic Pulmonary Fibrosis: Insights from Epidemiology to Prognosis.International journal of medical sciences · 2025Review
- The role of epigenetics in pulmonary fibrosis: recent advances in mechanistic insights and therapeutic implications.Frontiers in molecular biosciences · 2025Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Pulmonary fibrosis is a devastating disease characterized by accumulation of activated fibroblasts and scarring in the lung. While fibroblast activation in physiological wound repair reverses spontaneously, fibroblast activation in fibrosis is aberrantly sustained. Here we identified histone 3 lysine 9 methylation (H3K9me) as a critical epigenetic modification that sustains fibroblast activation by repressing the transcription of genes essential to returning lung fibroblasts to an inactive state. We show that the histone methyltransferase G9a (EHMT2) and chromobox homolog 5 (CBX5, also known as HP1α), which deposit H3K9me marks and assemble an associated repressor complex respectively, are essential to initiation and maintenance of fibroblast activation specifically through epigenetic repression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha gene (PPARGC1A, encoding PGC1α). Both TGFβ and increased matrix stiffness potently inhibit PGC1α expression in lung fibroblasts through engagement of the CBX5/G9a pathway. Inhibition of CBX5/G9a pathway in fibroblasts elevates PGC1α, attenuates TGFβ- and matrix stiffness-promoted H3K9 methylation, and reduces collagen accumulation in the lungs following bleomycin injury. Our results demonstrate that epigenetic silencing mediated by H3K9 methylation is essential for both biochemical and biomechanical fibroblast activation, and that targeting this epigenetic pathway may provide therapeutic benefit by returning lung fibroblasts to quiescence.
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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.