A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair.
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A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair. / Grose, Richard; Hutter, Caroline; Bloch, Wilhelm; Thorey, Irmgard; Watt, Fiona M; Fässler, Reinhard; Brakebusch, Cord; Werner, Sabine.
In: Development, Vol. 129, No. 9, 2002, p. 2303-15.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair.
AU - Grose, Richard
AU - Hutter, Caroline
AU - Bloch, Wilhelm
AU - Thorey, Irmgard
AU - Watt, Fiona M
AU - Fässler, Reinhard
AU - Brakebusch, Cord
AU - Werner, Sabine
N1 - Keywords: Animals; Antigens, CD29; Cell Adhesion; Cell Communication; Cell Division; Cell Movement; Cells, Cultured; Gene Expression; Keratinocytes; Mice; Mice, Knockout; Models, Biological; Neovascularization, Physiologic; Skin; Wound Healing
PY - 2002
Y1 - 2002
N2 - 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
AB - 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
M3 - Journal article
C2 - 11959837
VL - 129
SP - 2303
EP - 2315
JO - Development
JF - Development
SN - 0950-1991
IS - 9
ER -
ID: 5141515