Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1
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), 1480-1490. (doi:10.1242/jcs.03426).
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Description/Abstract
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.
| Item Type: | Article |
|---|---|
| ISSNs: | 0021-9533 (print) |
| Related URLs: | |
| Keywords: | rac, epidermis, wound healing, keratinocyte, proliferation, migration |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Divisions: | University Structure - Pre August 2011 > School of Biological Sciences |
| Item ID: | 55922 |
| Date Deposited: | 06 Aug 2008 |
| Last Modified: | 01 Jun 2011 17:07 |
| Contributors: | Tscharntke, Michael (Author) Pofahl, Ruth (Author) Chrostek-Grashoff, Anna (Author) Smyth, Neil (Author) Niessen, Carien (Author) Niemann, Catherin (Author) Hartwig, Benedikt (Author) Herzog, Volker (Author) Klein, Helmut W. (Author) Krieg, Thomas (Author) Brakebusch, Cord (Author) Haase, Ingo (Author) |
| Date: | 15 April 2007 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/55922 |
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