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

Two integrins, alpha 3 beta 1 and alpha 6 beta 4, 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 alpha 6 beta 4 integrin is indispensable for the stable anchorage of the epidermis to the underlying dermis. In contrast, the alpha 3 beta 1 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 alpha 3 beta 1 integrin, we used small interfering RNA to down-regulate the alpha 3 subunit in human keratinocytes. The resulting phenotype indicates that lack of alpha 3 beta 1 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 alpha 3 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 alpha 3 beta 1 integrin recapitulates crucial events governing keratinocyte migration associated with wound healing and tissue repair.