A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair.
Integrins are ubiquitous transmembrane receptors that play crucial roles in cell-cell and cell-matrix interactions. In this study, we have determined the effects of the loss of beta 1 integrins in keratinocytes in vitro and during cutaneous wound repair. Flow cytometry of cultured beta 1-deficient keratinocytes confirmed the absence of beta 1 integrins and showed downregulation of alpha 6 beta 4 but not of alpha v integrins. beta 1-null keratinocytes were characterised by poor adhesion to various substrates, by a reduced proliferation rate and by a strongly impaired migratory capacity. In vivo, the loss of beta 1 integrins in keratinocytes caused a severe defect in wound healing. beta 1-null keratinocytes showed impaired migration and were more densely packed in the hyperproliferative epithelium. Surprisingly, their proliferation rate was not reduced in early wounds and even increased in late wounds. The failure in re-epithelialisation resulted in a prolonged inflammatory response, leading to dramatic alterations in the expression of important wound-regulated genes. Ultimately, beta 1-deficient epidermis did cover the wound bed, but the epithelial architecture was abnormal. These findings demonstrate a crucial role of beta 1 integrins in keratinocyte migration and wound re-epithelialisation. Movies available on-line
Grose
Richard
R
Institute of Cell Biology, Department of Biology, ETH-Zürich, 8093 Zürich, Switzerland.
Hutter
Caroline
C
Bloch
Wilhelm
W
Thorey
Irmgard
I
Watt
Fiona M
FM
Fässler
Reinhard
R
Brakebusch
Cord
C
Werner
Sabine
S
D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D002455:Cell Division; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D015870:Gene Expression; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D012867:Skin / Q000098:blood supply / Q000293:injuries; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
D019012:Integrin beta1