| First Author | Tscharntke M | Year | 2007 |
| Journal | J Cell Sci | Volume | 120 |
| Issue | Pt 8 | Pages | 1480-90 |
| PubMed ID | 17389689 | Mgi Jnum | J:122061 |
| Mgi Id | MGI:3713043 | Doi | 10.1242/jcs.03426 |
| Citation | Tscharntke M, et al. (2007) Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1. J Cell Sci 120(Pt 8):1480-90 |
| abstractText | 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. |
