Re-epithelialization of normal human excisional wounds is associated with a switch from αvβ5 to αvβ6 integrins

Summary During cutaneous wound repair, keratinocytes move laterally across the wound surface. For this lateral movement epidermal cells must disassemble their tenacious connections to the basement membrane and their neighbouring cells, and express surface receptors that permit translocation over the wound surface extracellular matrix. If the basement membrane is disrupted, the epidermis migrates over a provisional matrix that contains fibrinogen, fibronectin, vitronectin and tenascin. Although α5β1 integrin, a fibronectin receptor, is expressed by human epidermis during reepithelialization of excisional and incisional wounds, the spatial and temporal patterns of vitronectin, tenascin, and other fibronectin receptors are less clear. Other potential receptors include αvβ5 for vitronectin and αvβ6 for fibronectin and tenascin. To study provisional matrix integrin expression during human wound healing, full-thickness 4-mm punch biopsies were performed on the inner surface of the upper arm in adult volunteers. At 3, 7 and 14 days after injury wound sites were excised, bisected, quick frozen in liquid nitrogen, and examined for the expression of α5, β1, αv, β5 and β6. At 3 days, α5β1 and αvβ5, but not αvβ6, appeared around the basal and suprabasalar cells of the migrating epidermis. At 7 days, α5β1, αvβ5, and αvβ6 appeared around the perimeter of the basal cells of the migrating epidermis. By 14 days, when re-epithelialization was complete, all basal and suprabasalar cells overlying the wound expressed α5β1 and αvβ6, but not αvβ5. Thus, αv appeared to switch its heterodimeric association from β5 to β6 subunit during re-epithelialization.