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 beta1 integrins in keratinocytes in vitro and during cutaneous wound repair. Flow cytometry of cultured beta1-deficient keratinocytes confirmed the absence of beta1 integrins and showed downregulation of alpha6beta4 but not of alphanu integrins. beta1-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 01 integrins in keratinocytes caused a severe defect in wound healing. beta1-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, beta1-deficient epidermis did cover the wound bed, but the epithelial architecture was abnormal. These findings demonstrate a crucial role of beta1 integrins in keratinocyte migration and wound re-epithelialisation.