Integrin α3 subunit regulates events linked to epithelial repair, including keratinocyte migration and protein expression

Two integrins, α3β1 and α6β4, are high-affinity receptors for laminin 332, the major laminin isoform of the dermal–epidermal junction, although they are thought to have different functions. Biological and genetic studies have firmly established that the α6β4 integrin is indispensable for the stable anchorage of the epidermis to the underlying dermis. In contrast, the α3β1 integrin is thought to be important for cell migration, although the issue is controversial, and both positive and negative effects have been reported. To address the function of α3β1 integrin, we used small interfering RNA to down-regulate the α3 subunit in human keratinocytes. The resulting phenotype indicates that lack of α3β1 integrin compromises intercellular adhesion and collective migration, while it enhances single cell migration with a concomitant increase of both focal adhesion kinase and extracellular signal-regulated kinase. In addition, down-regulation of integrin α3 subunit results in an increased expression of fibronectin and precursor laminin 332, two extracellular matrix proteins known to be up-regulated during wound healing. Thus, down-regulation of α3β1 integrin recapitulates crucial events governing keratinocyte migration associated with wound healing and tissue repair.