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

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

doi:10.1242/jcs.03426

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

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

Biomedicinsk Institut

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

92 Citationer (Scopus)

Abstract

Udgivelsesdato: 2007-Apr-15

Originalsprog	Engelsk
Tidsskrift	Journal of Cell Science
Vol/bind	120
Udgave nummer	Pt 8
Sider (fra-til)	1480-90
Antal sider	10
ISSN	0021-9533
DOI	https://doi.org/10.1242/jcs.03426
Status	Udgivet - 2007

Bibliografisk note

Keywords: Animals; Cell Adhesion; Cell Movement; Cell Proliferation; Epidermis; Keratinocytes; Wound Healing; rac1 GTP-Binding Protein

Adgang til dokumentet

10.1242/jcs.03426

Citationsformater

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; Haase, Ingo.

I: Journal of Cell Science, Bind 120, Nr. Pt 8, 2007, s. 1480-90.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@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.",

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TY - JOUR

T1 - Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1.

AU - Tscharntke, Michael

AU - Pofahl, Ruth

AU - Chrostek-Grashoff, Anna

AU - Smyth, Neil

AU - Niessen, Carien

AU - Niemann, Catherin

AU - Hartwig, Benedikt

AU - Herzog, Volker

AU - Klein, Helmut W

AU - Krieg, Thomas

AU - Brakebusch, Cord

AU - Haase, Ingo

N1 - Keywords: Animals; Cell Adhesion; Cell Movement; Cell Proliferation; Epidermis; Keratinocytes; Wound Healing; rac1 GTP-Binding Protein

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1242/jcs.03426

DO - 10.1242/jcs.03426

M3 - Journal article

C2 - 17389689

VL - 120

SP - 1480

EP - 1490

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - Pt 8

ER -