017 Laminin 10 in Wound Reepithelization and Angiogenesis

Abstract

Extracellular matrix laminins are the major noncollagenous components in the basement membrane zones (BMZ) and influence a variety of important biological processes including cell attachment, migration, and tissue development. A newly discovered laminin family member, laminin 10 (alpha 5, beta 1, and gamma 1), is found a major laminin present in the BMZs at the dermal-epidermal junction and dermal microvascular vessels. We examined the roles of laminin 10 in cutaneous wound repair in vitro and in vivo. Purified laminin 10 protein promoted human keratinocyte spreading and attachment, which is mediated by integrins. In human wound lesions, immunoperoxidase staining, with antibody 4C7 specific to laminin alpha 5 chain, stained strongly positive for laminin 10 in newly formed BMZs of epidermis and dermal blood vessels. Using a laminin 10 alpha 5 chain knockout mouse, excisional wounds in this model had abnormal reepithelialization and decreased granulation tissue formation. Transmission electron microscopy analysis of the BMZ of the mutant skin showed discontinuous lamina densa formation in areas between hemidesmosomes. In a porcine burn wound model, Reverse Transcription and Polymerase Chain Reaction analysis found significant higher expression of laminin 10 shortly after wounding and persisted through day 21, peaking at day 10. This expression pattern is consistent with the reconstitution of BMZs in the epidermis and microvascular blood vessels. These studies indicate that laminin 10 plays important roles in wound healing by promoting cell migration, BMZ assembly, reepithelialization, and angiogenesis. This study was supported by grants from NIH/NIAMES, DOD/DARPA and the Dermatology Foundation of South Florida.