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Wan, L. ; Jiang, D. ; Correa-Gallegos, D. ; Ramesh, P. ; Zhao, J. ; Ye, H. ; Zhu, S. ; Wannemacher, J. ; Volz, T.* ; Rinkevich, Y.

Connexin43 gap junction drives fascia mobilization and repair of deep skin wounds.

Matrix biol. 97, 58-71 (2021)
DOI PMC
Deep and voluminous skin wounds are repaired with scars, by mobilization of fibroblasts and extracellular matrix from fascia, deep below the skin. The molecular trigger of this novel repair mechanism is incompletely understood. Here we reveal that the gap junction alpha-1 protein (Connexin43, Cx43) is the key to patch repair of deep wounds. By combining full-thickness wound models with fibroblast lineage specific transgenic lines, we show Cx43 expression is substantially upregulated in specialized fibroblasts of the fascia deep beneath the skin that are responsible for scar formation. Using live imaging of fascia fibroblasts and fate tracing of the fascia extracellular matrix we show that Cx43 inhibition disrupts calcium oscillations in cultured fibroblasts and that this inhibits collective migration of fascia EPFs necessary to mobilize fascia matrix into open wounds. Cell-cell communication through Cx43 thus mediates matrix movement and scar formation, and is necessary for patch repair of voluminous wounds. These mechanistic findings have broad clinical implications toward treating fibrosis, aggravated scarring and impaired wound healing.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0945-053X
e-ISSN 1569-1802
Journal Matrix biology
Quellenangaben Volume: 97, Issue: , Pages: 58-71 Article Number: , Supplement: ,
Publisher Fischer
Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Regenerative Biology and Medicine (IRBM)
Institute of Lung Health and Immunity (LHI)
Grants Deutscher Akademischer Austauschdienst (DAAD)
Consejo Nacional de Ciencia y Tecnologia (CONACYT)
China Scholarship Council (CSC)
European Research Council Consolidator Grant
Fritz-Thyssen-Stiftung
German Research Foundation
Human Frontier Science Program Career Development Award