HUMAN KERATINOCYTE GROWTH-FACTOR EFFECTS IN A PORCINE MODEL OF EPIDERMAL WOUND-HEALING

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family (hence the alternative designation FGF-7). It is p roduced by stromal cells, but acts as a mitogen for epithelial cells. We examined the effects of topically applied KGF on healing of wounds in a porcine model. In partial-thickness wounds, KGF stimulated the ra te of reepithelialization (p <0.0002), associated with a thickening of the epidermis (p <0.0001). Epidermis from KGF-treated full-thickness wound sites was significantly thicker (0.31 +/- 0.22 mm) compared with mirror image control sites (0.18 +/- 0.12 mm) (p <0.0001). Moreover, the majority (77%) of KGF-treated wounds exhibited epidermis with a de ep rete ridge pattern as compared with control sites. These effects we re observed as early as 14 d and persisted for at least 4 wk. KGF trea tment also increased the number of serrated basal cells associated wit h increased deposition of collagen fibers in the superficial dermis ad jacent to the acanthotic epidermis. Electron microscopy revealed bette r developed hemidesmosomes associated with thicker bundles of tonofila ments in the serrated cells. The pattern of epidermal thickening obser ved in KGF-treated wounds resembled psoriasis. Psoriasis is a disease associated with epidermal thickening, parakeratosis as well as hyperpr oliferation that extends beyond the basal layer. In striking contrast to psoriasis, KGF-treated wounds exhibited normal orthokeratotic matur ation, and proliferation was localized to the basal cells. Our present findings have significant implications concerning the role of KGF as a paracrine modulator of epidermal proliferation and differentiation.