Epidermal integrin expression is upregulated rapidly in human fetal wound repair

Abstract Background/Purpose: The fetus heals skin wounds rapidly and scarlessly. The mechanisms that mediate the rapid reepithelialization that is seen in this process are unknown. Integrins are a family of cell surface receptors that bind fibronectin, tenascin, collagen, and other extracellular matrix proteins that are deposited rapidly in fetal wounds. The authors hypothesized that epidermal integrin receptors specific for fibronectin and other wound matrix proteins are upregulated rapidly during human fetal repair. Methods: To investigate the spatial and temporal expression of integrins in scarless fetal repair, fetal skin from six human abortuses (16 to 23 weeks' gestation) was transplanted subcutaneously into severe combined immunodeficient mice. After graft take, full-thickness incisional wounds were made in the grafts, and grafts were harvested at various time-points from 4 hours to 28 days after wounding. Integrin receptor protein expression was analyzed at each time-point using immunohistochemistry with monoclonal antibodies specific for the receptors that bind fibronectin, tenascin, collagen, and laminin (α5, αv, β6, α2, α3, α6, and β4). Results: In this model, wounded human fetal skin grafts reepithelialized rapidly (within 24 to 36 hours) and healed scarlessly. Within 4 hours of wounding, the grafts showed increased, suprabasal expression (α2, α3, α6, β4) or neoexpression (α5, αb, β6) of integrins at the epidermal wound edge. This increased expression persisted until reepithelialization was complete. Conclusions: Early upregulation of integrins in fetal wounds may permit rapid keratinocyte migration and reepithelialization, and may be important in limiting the induction of inflammatory mediators and scar.