ArticleMatrix biology : journal of the International Society for Matrix Biology2023
Autocrine IL-6 drives cell and extracellular matrix anisotropy in scar fibroblasts.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Fabrication of biomimetic topological micropattern arrays to induce anisotropic/isotropic orientation of fibroblast.MethodsX · 2026Article
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- Approaching Scarless Wound Healing: From Passive Anti-Fibrotic to Proactive and Programmable Pro-Regenerative Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
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- Revisiting the biophysical aspects of extracellular-matrix-mimicking hydrogels: what cells seeBiomaterials science · 2025Review
- Multicellular muscle-tendon bioprinting of mechanically optimized musculoskeletal bioactuators with enhanced force transmission.Science advances · 2025Article
- Characterisation and correction of polarisation effects in fluorescently labelled fibres.Journal of microscopy · 2025Article
- Skin organoid transplantation promotes tissue repair with scarless in frostbite.Protein & cell · 2025Article
- A Dynamical Analysis of the Alignment Mechanism Between Two Interacting Cells.Bulletin of mathematical biology · 2025Article
- The role of macrophages in hypertrophic scarring: molecular to therapeutic insights.Frontiers in immunology · 2025Review
- Derivation and simulation of a computational model of active cell populations: How overlap avoidance, deformability, cell-cell junctions and cytoskeletal forces affect alignment.PLoS computational biology · 2024Article
- Xylosyltransferase-Deficiency in Human Dermal Fibroblasts Induces Compensatory Myofibroblast Differentiation and Long-Term ECM Reduction.Biomedicines · 2024Article
- Imaging actin organisation and dynamics in 3D.Journal of cell science · 2024Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Fibrosis is associated with dramatic changes in extracellular matrix (ECM) architecture of unknown etiology. Here we exploit keloid scars as a paradigm to understand fibrotic ECM organization. We reveal that keloid patient fibroblasts uniquely produce a globally aligned ECM network in 2-D culture as observed in scar tissue. ECM anisotropy develops after rapid initiation of a fibroblast supracellular actin network, suggesting that cell alignment initiates ECM patterning. Keloid fibroblasts produce elevated levels of IL-6, and autocrine IL-6 production is both necessary and sufficient to induce cell and ECM alignment, as evidenced by ligand stimulation of normal dermal fibroblasts and treatment of keloid fibroblasts with the function blocking IL-6 receptor monoclonal antibody, tocilizumab. Downstream of IL-6, supracellular organization of keloid fibroblasts is controlled by activation of cell-cell adhesion. Adhesion formation inhibits contact-induced cellular overlap leading to nematic organization of cells and an alignment of focal adhesions. Keloid fibroblasts placed on isotropic ECM align the pre-existing matrix, suggesting that focal adhesion alignment leads to active anisotropic remodeling. These results show that IL-6-induced fibroblast cooperativity can control the development of a nematic ECM, highlighting both IL-6 signaling and cell-cell adhesions as potential therapeutic targets to inhibit this common feature of fibrosis.
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Registered trials
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