EPIDERMAL INTEGRIN EXPRESSION IS UP-REGULATED RAPIDLY IN HUMAN FETAL WOUND REPAIR

Background/Purpose: The fetus heals skin wounds rapidly and scarlessly . The mechanisms that mediate the rapid reepithelialization that is se en in this process are unknown. Integrins are a family of cell surface receptors that bind fibronectin, tenascin, collagen, and other extrac ellular matrix proteins that are deposited rapidly in fetal wounds. Th e authors hypothesized that epidermal integrin receptors specific for fibronectin and other wound matrix proteins are upregulated rapidly du ring human fetal repair. Methods: To investigate the spatial and tempo ral expression of integrins in scarless fetal repair, fetal skin from six human abortuses (16 to 23 weeks' gestation) was transplanted subcu taneously 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 wo unding. 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 lamin in (alpha(5), alpha V, beta 6, alpha 2, alpha 3, alpha 6, and beta 4). Results: In this model, wounded human fetal skin grafts reepitheliali zed rapidly (within 24 to 36 hours) and healed scarlessly. Within 4 ho urs of wounding, the grafts showed increased, suprabasal expression (a lpha 2, alpha 3, alpha 6, beta 4) or neoexpression (alpha 5, alpha b, beta 6) of integrins at the epidermal wound edge. This increased expre ssion persisted until reepithelialization was complete. Conclusions: E arly upregulation of integrins in fetal wounds may permit rapid kerati nocyte migration and reepithelialization, and may be important in limi ting the induction of inflammatory mediators and scar. Copyright (C) 1 998 by W.B. Saunders Company.