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Myofibroblasts (MFs) are responsible for both physiological wound and scar contraction. However, it is not known whether these cells act individually to contract the surrounding matrix or whether they behave in a coordinated manner. Therefore, we studied intercellular junctions of primary human MFs derived from patients with Dupuytren's disease, a fibrotic disorder of the dermis and subdermal tissues of the palm. The cells were maintained in anchored three-dimensional collagen lattices to closely mimic conditions in vivo. We found that selective blockade of adherens, mechanosensitive, or gap junctions effectively inhibited contraction of the collagen matrices and downregulated the MF phenotype. Our data indicate that MFs in part function as a coordinated cellular syncytium, and disruption of intercellular communication may provide a therapeutic target in diseases characterized by an overabundance of these contractile cells.

Type

Journal article

Journal

The Journal of investigative dermatology

Publication Date

12/2013

Volume

133

Pages

2664 - 2671

Addresses

1] Kennedy Institute of Rheumatology, University of Oxford, London, UK [2] Department of Plastic and Reconstructive Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands.

Keywords

Cells, Cultured, Intercellular Junctions, Gap Junctions, Fibroblasts, Giant Cells, Skin, Humans, Collagen, Cadherins, RNA, Small Interfering, Microscopy, Fluorescence, Cell Communication, Isometric Contraction, Phenotype, Dupuytren Contracture, Myofibroblasts