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Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1

Record type: Article

To address the functions of Rac1 in keratinocytes of the basal epidermal layer and in the outer root sheath of hair follicles, we generated transgenic mice expressing a dominant inhibitory mutant of Rac, N17Rac1, under the control of the keratin 14 promoter. These mice do not exhibit an overt skin phenotype but show protracted skin wound re-epithelialization. Investigation into the underlying mechanisms revealed that in vivo both proliferation of wound-edge keratinocytes and centripetal migration of the neo-epidermis were impaired. Similar results were obtained in mice with an epidermis-specific deletion of Rac1. Primary epidermal keratinocytes that expressed the N17Rac1 transgene were less proliferative than control cells and showed reduced ERK1/2 phosphorylation upon growth factor stimulation. Adhesion, spreading, random migration and closure of scratch wounds in vitro were significantly inhibited on collagen I and, to a lesser extent, on fibronectin. Stroboscopic analysis of cell dynamics (SACED) of N17Rac1 transgenic and control keratinocytes identified decreased lamella-protrusion persistence in connection with increased ruffle frequency as a probable mechanism for the observed impairment of keratinocyte adhesion and migration. We conclude that Rac1 is functionally required for normal epidermal wound healing and, in this context, exerts a dual function – namely the regulation of keratinocyte proliferation and migration.

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Citation

Tscharntke, Michael, Pofahl, Ruth, Chrostek-Grashoff, Anna, Smyth, Neil, Niessen, Carien, Niemann, Catherin, Hartwig, Benedikt, Herzog, Volker, Klein, Helmut W., Krieg, Thomas, Brakebusch, Cord and Haase, Ingo (2007) Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1 Journal of Cell Science, 120, (8), pp. 1480-1490. (doi:10.1242/jcs.03426).

More information

Published date: 15 April 2007
Keywords: rac, epidermis, wound healing, keratinocyte, proliferation, migration

Identifiers

Local EPrints ID: 55922
URI: http://eprints.soton.ac.uk/id/eprint/55922
ISSN: 0021-9533
PURE UUID: 826ce647-84f5-4abd-be81-b45ca5e191b2

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Date deposited: 06 Aug 2008
Last modified: 17 Jul 2017 14:31

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Contributors

Author: Michael Tscharntke
Author: Ruth Pofahl
Author: Anna Chrostek-Grashoff
Author: Neil Smyth
Author: Carien Niessen
Author: Catherin Niemann
Author: Benedikt Hartwig
Author: Volker Herzog
Author: Helmut W. Klein
Author: Thomas Krieg
Author: Cord Brakebusch
Author: Ingo Haase

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