Wound Healing in the α2β1 Integrin-Deficient Mouse: Altered Keratinocyte Biology and Dysregulated Matrix Metalloproteinase Expression

The α2β1 integrin, a collagen/laminin receptor, is expressed at high level in the basal cell layer of the epidermis. To define the role of the α2β1 integrin in wound healing, wound repair was extensively evaluated in wild-type and α2-null mice in vivo. In addition, the impact of α2β1 integrin-deficiency on the function of primary murine keratinocytes in vitro was analyzed. Our in vivo findings demonstrate that genetic deletion of the α2β1 integrin does not significantly alter the rate of re-epithelialization, collagen deposition, or tensile strength during wound closure in mice. In marked contrast to the observed similarities in wound healing, deletion of the α2β1 integrin resulted in a dramatic increase in neoangiogenesis in the wound microenvironment. In contrast to in vivo studies, primary keratinocytes from α2-null mice adhered poorly and displayed impaired migration on type I collagen in vitro. We demonstrate that α2β1 integrin-ligation negatively regulates expression of genes including matrix metalloproteinases both in vivo and in vitro. Furthermore, the changes in gene expression could potentially account for relatively normal wound healing in the α2-deficient mouse and our recent observation that suggests an antiangiogenic role for the α2β1 integrin in vivo.