Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1.
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of Cell Science |
Volume | 120 |
Issue number | Pt 8 |
Pages (from-to) | 1480-90 |
Number of pages | 10 |
ISSN | 0021-9533 |
DOIs | |
Publication status | Published - 2007 |
Bibliographical note
Keywords: Animals; Cell Adhesion; Cell Movement; Cell Proliferation; Epidermis; Keratinocytes; Wound Healing; rac1 GTP-Binding Protein
ID: 5140853