title: Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization.
abstract: For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man.
authors.affiliation: Schools of Biochemistry and Physiology & Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Nunan
authors.affiliation: Schools of Biochemistry and Physiology & Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Campbell
authors.affiliation: Schools of Biochemistry and Physiology & Pharmacology, University of Bristol, Bristol BS8 1TD, UK; Department of Pathology, Nagasaki University, Nagasaki 852-8523, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mori
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany; Faculty of Medicine, University of Muenster, 48149 Muenster, Germany.
authors.forename: Mara E
authors.initials: ME
authors.lastname: Pitulescu
authors.affiliation: School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Harding
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany; Faculty of Medicine, University of Muenster, 48149 Muenster, Germany.
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: Schools of Biochemistry and Physiology & Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Nobes
authors.affiliation: Schools of Biochemistry and Physiology & Pharmacology, University of Bristol, Bristol BS8 1TD, UK; School of Medicine, Cardiff University, Cardiff CF14 4XN, UK. Electronic address: paul.martin@bristol.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D036387:Ephrin-B1 / Q000502:physiology*; D036388:Ephrin-B2 / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055503:Protein Multimerization; D062326:Re-Epithelialization; D036081:Receptors, Eph Family / Q000378:metabolism; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism*
chemical_list: D036387:Ephrin-B1; D036388:Ephrin-B2; D036081:Receptors, Eph Family