ArticleCellular and molecular bioengineering2017
Matrix Mechanics Influence Fibroblast-Myofibroblast Transition by Directing the Localization of Histone Deacetylase 4.
Article in Cellular and molecular bioengineering, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- ECM-Stiffness Mediated Persistent Fibroblast Activation Requires Integrin and Formin Dependent Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Estrogen receptor beta activates regenerating family member 1 beta to modulate fibroblast function in pelvic organ prolapse.Journal of molecular histology · 2026Article
- Mechanical forces orchestrate the epigenetic landscape of oral mesenchymal stem/progenitor cell fate in dental and periodontal tissues.Frontiers in cell and developmental biology · 2026Review
- Epigenetic Reprogramming Via Sodium Butyrate Induces Corneal Myofibroblast Dedifferentiation In Vitro and Inhibits Fibrosis In Vivo.Investigative ophthalmology & visual science · 2025Article
- Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow twitch muscles.Scientific reports · 2025Article
- Activin A Inhibitory Peptides Suppress Fibrotic Pathways by Targeting Epithelial-Mesenchymal Transition and Fibroblast-Myofibroblast Transformation in Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2025Article
- Role of Quercetin in Diabetic Cardiomyopathy.Plants (Basel, Switzerland) · 2024Review
- Application of biomechanics in tumor epigenetic research.Mechanobiology in medicine · 2024Review
- Biphasic regulation of epigenetic state by matrix stiffness during cell reprogramming.Science advances · 2024Article
- FOXM1 Participates in Scleral Remodeling in Myopia by Upregulating APOA1 Expression Through METTL3/YTHDF2.Investigative ophthalmology & visual science · 2024Article
- Actomyosin Activity and Piezo1 Activity Synergistically Drive Urinary System Fibroblast Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Nutriepigenomics in Environmental-Associated Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Research progress on the relationship between the TOR signaling pathway regulator, epigenetics, and tumor development.Frontiers in genetics · 2022Review
- Mechanical Cues Regulate Histone Modifications and Cell Behavior.Stem cells international · 2022Review
- Nuclear mechanosensing drives chromatin remodelling in persistently activated fibroblasts.Nature biomedical engineering · 2021Article
- Effects of forces on chromatin.APL bioengineering · 2021Review
- Engineered microenvironment for the study of myofibroblast mechanobiology.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2021Article
- Mechanical regulation of histone modifications and cell plasticity.Current opinion in solid state & materials science · 2020Article
- Effects of substrate patterning on cellular spheroid growth and dynamics measured by gradient light interference microscopy (GLIM).Journal of biophotonics · 2019Article
- Matrix stiffness induces a tumorigenic phenotype in mammary epithelium through changes in chromatin accessibility.Nature biomedical engineering · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe propagation of mechanochemical signals from the extracellular matrix to the cell nucleus has emerged as a central feature in regulating cellular differentiation and de-differentiation. This process of outside-in signaling and the associated mechanotransduction pathways have been well described in numerous developmental and pathological contexts. However, it remains less clear how mechanotransduction influences the activity of chromatin modifying enzymes that direct gene expression programs.
objectivesThe primary objective of this study was to explore how matrix mechanics and geometric confinement influence histone deacetylase (HDAC) activity in fibroblast culture.
methodsPolyacrylamide hydrogels were formed and functionalized with fibronectin patterns using soft lithography. Primary mouse embryonic fibroblasts (MEFs) were cultured on the islands until confluent, fixed, and immunolabeled for microscopy.
resultsAfter 24 h MEFs cultured on soft hydrogels (0.5 kPa) show increased expression of class I HDACs relative to MEFs cultured on stiff hydrogels (100 kPa). A member of the class II family, HDAC4 shows a similar trend; however, there is a pronounced cytoplasmic localization on soft hydrogels suggesting a role in outside-in cytoplasmic signaling. Pharmacological inhibitor studies suggest that the opposing activities of extracellular related kinase 1/2 (ERK) and protein phosphatase 2a (PP2a) influence the localization of HDAC4. MEFs cultured on the soft hydrogels show enhanced expression of markers associated with a fibroblast-myofibroblast transition (Paxillin, αSMA).
conclusionsWe show that the phosphorylation state and cellular localization of HDAC4 is influenced by matrix mechanics, with evidence for a role in mechanotransduction and the regulation of gene expression associated with fibroblast-myofibroblast transitions. This work establishes a link between outside-in signaling and epigenetic regulation, which will assist efforts aimed at controlling gene regulation in engineered extracellular matrices.
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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.