Integrin α3β1 inhibits directional migration and wound re-epithelialization in the skin

Re-epithelialization after skin wounding requires both migration and hyperproliferation of keratinocytes. Laminin-332 is deposited during migration over the provisional matrix. To investigate the function of the laminin-332 binding integrin alpha 3 beta 1 in wound re-epithelialization, we generated Itga3(flox/flox); K14-Cre mice lacking the alpha 3 subunit specifically in the basal layer of the epidermis. These mice are viable but display several skin defects, including local inflammation, hair loss, basement membrane duplication and microblistering at the dermal-epidermal junction, whereas hemidesmosome assembly and keratinocyte differentiation are not impaired. Wound healing is slightly faster in the absence of integrin alpha 3 beta 1, whereas proliferation, the distribution of other integrins and the deposition of basement membrane proteins in the wound bed are unaltered. In vitro, cell spreading is rescued by increased surface expression of alpha 6 beta 1 integrin in the absence of integrin alpha 3. The alpha 3-deficient keratinocytes migrate with an increased velocity and persistence, whereas proliferation, growth factor signaling, hemidesmosome assembly, and laminin-332 deposition appeared to be normal. We suggest that integrin alpha 3 beta 1 delays keratinocyte migration during wound reepithelialization, by binding to the laminin-332 that is newly deposited on the wound bed.