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Myofibroblast Development Is Characterized by Specific Cell-Cell Adherens Junctions
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Myofibroblasts of wound granulation tissue, in contrast to dermal fibroblasts, join stress fibers at sites of cadherin-type intercellular adherens junctions (AJs). However, the function of myofibroblast AJs, their molecular composition, and the mechanisms of their formation are largely unknown. We demonstrate that fibroblasts change cadherin expression from N-cadherin in early wounds to OB-cadherin in contractile wounds, populated with α-smooth muscle actin (α-SMA)-positive myofibroblasts. A similar shift occurs during myofibroblast differentiation in culture and seems to be responsible for the homotypic segregation of α-SMA-positive and -negative fibroblasts in suspension. AJs of plated myofibroblasts are reinforced by α-SMA–mediated contractile activity, resulting in high mechanical resistance as demonstrated by subjecting cell pairs to hydrodynamic forces in a flow chamber. A peptide that inhibits α-SMA–mediated contractile force causes the reorganization of large stripe-like AJs to belt-like contacts as shown for enhanced green fluorescent protein-α–catenin-transfected cells and is associated with a reduced mechanical resistance. Anti-OB-cadherin but not anti-N-cadherin peptides reduce the contraction of myofibroblast-populated collagen gels, suggesting that AJs are instrumental for myofibroblast contractile activity.
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“indeed, during the fibroblast-tomyofibroblast transition a decrease of N-cadherin expression and an increase of OB-cadherin/cadherin-11 have been described [21].”
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Metadata
- Authors
- Hinz, B., Pittet, P., Smith-Clerc, J., Chaponnier, C., & Meister, J.-J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- University of Geneva (CH)
- Venue
- Molecular Biology of the Cell
- Published
- 2004-09
- Volume
- 15
- Issue
- 9
- Pages
- 4310-4320
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC515361
- OpenAlex
- W2096945892
- Cited by
- 231
- References
- 80
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 10 · 2023: 7 · 2022: 11 · 2021: 15 · 2020: 13 · 2019: 7 · 2018: 14 · 2017: 8 · 2016: 8 · 2015: 16 · 2014: 18 · 2013: 12 · 2012: 16
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Biogen
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (102150, 3100A0)
- Université de Genève
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- myofibroblast differentiation, adherens junctions, N-cadherin, alpha-smooth muscle actin, cell contractility, alpha-catenin, stress fibers, mechanical resistance, collagen gel contraction, fibroblast differentiation
- MeSH terms
- Actins, Animals, Biomechanical Phenomena, Cell Differentiation, Cells, Cultured, Collagen, Female, Fibroblasts, Gels, Models, Biological, Skin, Wound Healing, Cadherins, Rats, Wistar, Adherens Junctions, Myoblasts, Rats
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