Wound healing is defective in mice lacking tetraspanin CD151

The tetraspanin CD151 forms complexes in epithelial cell membranes with laminin-binding integrins alpha 6 beta 4, alpha 3 beta 1, and alpha 6 beta 1, and modifies integrin-mediated cell migration in vitro. We demonstrate in this study that CD151 expression is upregulated in a distinct temporal and spatial pattern during wound healing, particularly in the migrating epidermal tongue at the wound edge, suggesting a role for CD151 in keratinocyte migration. We show that healing is significantly impaired in CD151-null mice, with wounds gaping wider at 7 days post-injury. The rate of re-epithelialization of the CD151-null wounds is adversely affected, with significantly less wound area being covered by migrating epidermal cells. Our studies reveal that although laminin levels are similar in wildtype and CD151-null wounds, the organization of the laminin in the basement membrane is impaired. Furthermore, upregulation of alpha 6 and beta 4 integrin expression is adversely affected in CD151-null mice wounds. In contrast, we find no significant effect of CD151 gene knockout on alpha 3 and beta 1 integrin expression in wound repair. We suggest that mice lacking the CD151 gene are defective in wound healing, primarily owing to impairment of the re-epithelialization process. This may be due to defective basement membrane formation and epithelial cell adhesion and migration.