Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin

Dongsheng Jiang, Simon Christ, Donovan Correa-Gallegos, Pushkar Ramesh, Shruthi Kalgudde Gopal, Juliane Wannemacher, Christoph H. Mayr, Valerio Lupperger, Qing Yu, Haifeng Ye, Martin Mück-Häusl, Vijayanand Rajendran, Li Wan, Juan Liu, Ursula Mirastschijski, Thomas Volz, Carsten Marr, Herbert B. Schiller and Yuval Rinkevich ()
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Dongsheng Jiang: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Simon Christ: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Donovan Correa-Gallegos: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Pushkar Ramesh: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Shruthi Kalgudde Gopal: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Juliane Wannemacher: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Christoph H. Mayr: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Systems Medicine of Chronic Lung Disease
Valerio Lupperger: Helmholtz Zentrum München, Institute of Computational Biology
Qing Yu: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Haifeng Ye: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Martin Mück-Häusl: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Vijayanand Rajendran: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Li Wan: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Juan Liu: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine
Ursula Mirastschijski: Mira-Beau gender esthetics
Thomas Volz: Technical University of Munich, School of Medicine, Klinikum rechts der Isar
Carsten Marr: Helmholtz Zentrum München, Institute of Computational Biology
Herbert B. Schiller: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Systems Medicine of Chronic Lung Disease
Yuval Rinkevich: Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dish – SCAD). We observe that injury triggers a swarming-like collective cell migration of fascia fibroblasts that progressively contracts the skin and form scars. Swarming is exclusive to fascia fibroblasts, and requires the upregulation of N-cadherin. Both swarming and N-cadherin expression are absent from fibroblasts in the upper skin layers and the oral mucosa, tissues that repair wounds with minimal scar. Impeding N-cadherin binding inhibits swarming and skin contraction, and leads to reduced scarring in SCADs and in animals. Fibroblast swarming and N-cadherin thus provide therapeutic avenues to curtail fascia mobilisation and pathological fibrotic responses across a range of medical settings.

Date: 2020
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DOI: 10.1038/s41467-020-19425-1

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