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The behavior of the keratinocyte during the initial stages of cutaneous wound repair has been the subject of intense investigation. Most of these studies have focused on the lateral edges of wounds as the source of activated keratinocytes. Less attention has been directed towards elucidating the role of the appendageal structures as sources of keratinocytes for re-epithelialization, particularly the sweat apparatus. Surgical wounds of specific depths were created in pig skin, above and below hair follicles, and wound healing was allowed to take place in a setting in which lateral ingrowth of keratinocytes by migration was prevented. In this manner, all re-epithelialization occurred from residual appendageal structures. In those wounds where only sweat gland elements remained, an epithelium formed that had clinical, morphologic, and protein electrophoretic features closer to palmar/plantar or mucosal-like epithelia. In contrast, wounds that retained elements of the hair follicle healed faster and the resultant epithelium clinically, morphologically, and biochemically resembled the surrounding nonwounded epidermis. These findings establish that the sweat apparatus is capable of re-epithelializing the skin surface after a major cutaneous wound, but may not be capable of mimicking the epidermis.

Primary human dermal fibroblasts isolated from the medial aspect of the proximal forearm of young and old donors were compared for the expression of interstitial collagenase, 72 kDa type IV collagenase, the tissue inhibitor of metalloproteinase type 1, and pro-alpha 2 (I) collagen mRNA at basal levels and after stimulation with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate. Higher basal and induced steady-state mRNA levels of interstitial collagenase were found in the cells from older donors. Ratios of basal and induced steady-state mRNA levels of interstitial collagenase to pro-alpha 2 (I) collagen, and interstitial collagenase to the tissue inhibitor of metalloproteinases type 1 were also higher in the cells from older donors. Seventy-two kiloDalton type IV collagenase and pro-alpha 2 (I) collagen mRNA showed similar levels of expression in the cells from young and old donors and were not altered by treatment with 12-O-tetradecanoyl-phorbol-13-acetate. Transient transfection assays with the interstitial collagenase promoter linked to a reporter gene showed increased activity of the reporter in cell strains with high interstitial collagenase mRNA levels. Mobility shift assays demonstrated increased binding activity to the specific 12-O-tetradecanoyl-phorbol-13-acetate response element in nuclear extracts from the cell strains with higher induced collagenase mRNA levels and higher reporter gene activity. These findings are consistent with the observed phenotype of interstitial collagenase and its specific tissue inhibitor in the senescent fibroblast aging model.