@article{798d8450589211dd8d9f000ea68e967b,
title = "Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1.",
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.",
author = "Michael Tscharntke and Ruth Pofahl and Anna Chrostek-Grashoff and Neil Smyth and Carien Niessen and Catherin Niemann and Benedikt Hartwig and Volker Herzog and Klein, {Helmut W} and Thomas Krieg and Cord Brakebusch and Ingo Haase",
note = "Keywords: Animals; Cell Adhesion; Cell Movement; Cell Proliferation; Epidermis; Keratinocytes; Wound Healing; rac1 GTP-Binding Protein",
year = "2007",
doi = "10.1242/jcs.03426",
language = "English",
volume = "120",
pages = "1480--90",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "The/Company of Biologists Ltd.",
number = "Pt 8",
}