Restoration of the basement membrane after wounding: a hallmark of young human skin altered with aging

In skin, the basement membrane at the dermalepidermal junction (DEJ-BM) is an important structure that tightly binds the epidermis to the dermis, and acts as a permeability barrier that controls exchange of macromolecules. Repair of the DEJ-BM during wound healing is important for restoration of skin functional properties after wounding. Here, we used a CO2 laser to perform partial thickness wounds in human volunteers, and directly compared wound repair in healthy young and aged individuals, focusing on the DEJ-BM. Our results show that the DEJ-BM is restored within four weeks after partial thickness wounds in young adults. We identified laminin-gamma 2 as preferred substrate for keratinocytes during reepithelialization of partial thickness human wounds. Laminin-gamma 2 is expressed continuously by migrating keratinocytes during reepithelialization, whereas collagen IV and collagen VII are deposited after wound closure. In contrast, our study shows that the DEJ-BM restoration following wounding is deficient in elderly individuals. Specifically, COL7A2 was barely increased during wound repair in aged skin and, as a result, the DEJ-BM in elderly skin was not restored and showed abnormal structure. Our data suggest that ameliorating the quality of the DEJ-BM restoration is a promising therapeutic approach to improve the quality of repaired skin in the elderly.