Myofibroblast development is characterized by specific cell-cell adherens junctions

Hinz, B.; Pittet, P.; Smith-Clerc, J.; Chaponnier, C.; Meister, J.-J.

doi:10.1091/mbc.e04-05-0386

Cited by 231Cellular Mechanics and InteractionsWound Healing and TreatmentsCell Adhesion Molecules Research

Myofibroblast development is characterized by specific cell-cell adherens junctions

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Hinz, B., Pittet, P., Smith-Clerc, J., Chaponnier, C., Meister, J.-J.·2004·Molecular Biology of the Cell

DOI 10.1091/mbc.e04-05-0386PMC PMC515361

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Abstract

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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During fibroblast-to-myofibroblast transition, N-cadherin levels fall while OB-cadherin/cadherin-11 levels rise.
“indeed, during the fibroblast-tomyofibroblast transition a decrease of N-cadherin expression and an increase of OB-cadherin/cadherin-11 have been described [21].”
From Dermal fibroblast-to-myofibroblast transition sustained by αvß3 integrin-ILK-Snail1/Slug signaling is a common feature for hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders (2018) · cites this paper as [21]

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Self-citation

Authors: Hinz, B., Pittet, P., Smith-Clerc, J., Chaponnier, C., & Meister, J.-J.
Affiliations: École Polytechnique Fédérale de Lausanne (CH)
University of Geneva (CH)
ORCID: Hinz, B.
Chaponnier, C.
Meister, J.-J.
Venue: Molecular Biology of the Cell
Publisher: American Society for Cell Biology (ASCB)
Published: 2004-09
Volume: 15
Issue: 9
Pages: 4310-4320
ISSN: 1059-1524 (ISSN-L)
1939-4586
DOI: 10.1091/mbc.e04-05-0386
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 › Rehabilitation › 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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Myofibroblast development is characterized by specific cell-cell adherens junctions

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