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J Cell Biol. 2018 Dec 3;217(12):4267-4283. doi: 10.1083/jcb.201804048. Epub 2018 Sep 18.

Occluding junctions as novel regulators of tissue mechanics during wound repair.

Author information

1
Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal lara.carvalho@nms.unl.pt.
2
Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
3
Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, Lisbon, Portugal.
4
Centro de Física Teórica e Computacional, Universidade de Lisboa, Campo Grande, Lisbon, Portugal.
5
Institute of Science and Technology Austria, Klosterneuburg, Austria.
6
Centre National de la Recherche Scientifique/Sorbonne Université/Team Mamba, French Institute for Research in Computer Science and Automation Paris, Laboratoire Jacques-Louis Lions, BC187, Paris, France.
7
Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Lisbon, Portugal.
8
Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal antonio.jacinto@nms.unl.pt.
9
The Discoveries Centre for Regenerative and Precision Medicine, Universidade NOVA de Lisboa, Lisbon, Portugal.

Abstract

In epithelial tissues, cells tightly connect to each other through cell-cell junctions, but they also present the remarkable capacity of reorganizing themselves without compromising tissue integrity. Upon injury, simple epithelia efficiently resolve small lesions through the action of actin cytoskeleton contractile structures at the wound edge and cellular rearrangements. However, the underlying mechanisms and how they cooperate are still poorly understood. In this study, we combine live imaging and theoretical modeling to reveal a novel and indispensable role for occluding junctions (OJs) in this process. We demonstrate that OJ loss of function leads to defects in wound-closure dynamics: instead of contracting, wounds dramatically increase their area. OJ mutants exhibit phenotypes in cell shape, cellular rearrangements, and mechanical properties as well as in actin cytoskeleton dynamics at the wound edge. We propose that OJs are essential for wound closure by impacting on epithelial mechanics at the tissue level, which in turn is crucial for correct regulation of the cellular events occurring at the wound edge.

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