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DEVELOPMENT AND DISEASE |
1 Institute of Cell Biology, Department of Biology, ETH-Zürich, 8093 Zürich, Switzerland
2 Keratinocyte Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK
3 Institute of Anatomy, University of Cologne, D-50931 Köln, Germany
4 Department of Experimental Pathology, Lund University, S-221 85 Lund, Sweden
5 Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany
* Present address: Viral Carcinogenesis Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK
The first two authors have equally contributed to this work
Author for correspondence (e-mail: sabine.werner{at}cell.biol.ethz.ch)
Accepted 4 February 2002
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 ß1 integrins in keratinocytes in vitro and during cutaneous wound repair. Flow cytometry of cultured ß1-deficient keratinocytes confirmed the absence of ß1 integrins and showed downregulation of 
6ß4 but not of v integrins. ß1-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 ß1 integrins in keratinocytes caused a severe defect in wound healing. ß1-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, ß1-deficient epidermis did cover the wound bed, but the epithelial architecture was abnormal. These findings demonstrate a crucial role of ß1 integrins in keratinocyte migration and wound re-epithelialisation.
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Key words: Integrin, Migration, Epidermis, Mouse, Wound
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