ArticleCirculation research2020
Infarct Collagen Topography Regulates Fibroblast Fate via p38-Yes-Associated Protein Transcriptional Enhanced Associate Domain Signals.
Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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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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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Pooled it
- Ubiquitin-Related Proteostatic Programs in Cycling Fibroblast-Lineage Remodeling After Myocardial Ischemic Injury: A Hypothesis Informed by Single-Cell and Spatial Transcriptomics.International journal of molecular sciences · 2026Review
- Doxorubicin exposure leads to cardiac fibroblast dysregulation and worsens fibrotic remodeling in the pathological heart.Journal of molecular and cellular cardiology plus · 2026Article
- Fabrication of biomimetic topological micropattern arrays to induce anisotropic/isotropic orientation of fibroblast.MethodsX · 2026Article
- Cardiac fibroblasts in myocardial injury and heart failure.European heart journal · 2026Review
- Micro Pattern-Based 3D Cell Culture Platform: An Overview of Technologies and Applications.Exploration (Beijing, China) · 2026Review
- Free-Breathing Multi-Slice Co-Registered Cardiac T1, T2, and ADC Mapping With Spin-Echo Echo Planar Imaging.Magnetic resonance in medicine · 2026Article
- Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy.Science (New York, N.Y.) · 2025Article
- Cell type specificity of Hippo-YAP signaling in cardiac development and disease.Journal of molecular and cellular cardiology · 2025Review
- Hybrid hydrogel-extracellular matrix scaffolds identify biochemical and mechanical signatures of cardiac ageing.Nature materials · 2025Article
- Signals from the extracellular matrix: Region- and sex-specificity in cardiac aging.Current opinion in cell biology · 2025Review
- The mechanobiology of fibroblast activation in disease.APL bioengineering · 2025Review
- EDA Fibronectin Microarchitecture and YAP Translocation during Wound Closure.ACS biomaterials science & engineering · 2025Article
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Effects of Cell Seeding Density, Extracellular Matrix Composition, and Geometry on Yes-Associated Protein Translocation in Corneal Fibroblasts.International journal of molecular sciences · 2025Article
- Emerging biomedical technologies for scarless wound healing.Bioactive materials · 2024Review
- The Multifaceted Roles of Hippo-YAP in Cardiovascular Diseases.Cardiovascular toxicology · 2024Review
- Matrix Architecture and Mechanics Regulate Myofibril Organization, Costamere Assembly, and Contractility in Engineered Myocardial Microtissues.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- EDA Fibronectin Microarchitecture and YAP Translocation During Wound Closure.bioRxiv : the preprint server for biology · 2024Article
- Natural Compounds and Biomimetic Engineering to Influence Fibroblast Behavior in Wound Healing.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleMyocardial infarction causes spatial variation in collagen organization and phenotypic diversity in fibroblasts, which regulate the heart's ECM (extracellular matrix). The relationship between collagen structure and fibroblast phenotype is poorly understood but could provide insights regarding the mechanistic basis for myofibroblast heterogeneity in the injured heart.
objectiveTo investigate the role of collagen organization in cardiac fibroblast fate determination. METHODS AND
resultsBiomimetic topographies were nanofabricated to recapitulate differential collagen organization in the infarcted mouse heart. Here, adult cardiac fibroblasts were freshly isolated and cultured on ECM topographical mimetics for 72 hours. Aligned mimetics caused cardiac fibroblasts to elongate while randomly organized topographies induced circular morphology similar to the disparate myofibroblast morphologies measured in vivo. Alignment cues also induced myofibroblast differentiation, as >60% of fibroblasts formed αSMA (α-smooth muscle actin) stress fibers and expressed myofibroblast-specific ECM genes like Postn (periostin). By contrast, random organization caused 38% of cardiac fibroblasts to express αSMA albeit with downregulated myofibroblast-specific ECM genes. Coupling topographical cues with the profibrotic agonist, TGFβ (transforming growth factor beta), additively upregulated myofibroblast-specific ECM genes independent of topography, but only fibroblasts on flat and randomly oriented mimetics had increased percentages of fibroblasts with αSMA stress fibers. Increased tension sensation at focal adhesions induced myofibroblast differentiation on aligned mimetics. These signals were transduced by p38-YAP (yes-associated protein)-TEAD (transcriptional enhanced associate domain) interactions, in which both p38 and YAP-TEAD (yes-associated protein transcriptional enhanced associate domain) binding were required for myofibroblast differentiation. By contrast, randomly oriented mimetics did not change focal adhesion tension sensation or enrich for p38-YAP-TEAD interactions, which explains the topography-dependent diversity in fibroblast phenotypes observed here.
conclusionsSpatial variations in collagen organization regulate cardiac fibroblast phenotype through mechanical activation of p38-YAP-TEAD signaling, which likely contribute to myofibroblast heterogeneity in the infarcted myocardium.
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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.