Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair

Wound-healing disorders are a therapeutic problem of extensive clinical imp ortance. Leptin-deficient ob/ob mice are characterized by a severely delaye d mound healing that has been explained by the mild diabetic phenotype of t hese animals. Here we demonstrate that systemically and topically supplemen ted leptin improved re-epithelialization of wounds in ob/ob mice. Leptin co mpletely reversed the atrophied morphology of the migrating epithelial tong ue observed at the wound margins of leptin-deficient animals into a well-or ganized hyperproliferative epithelium. Moreover, topically supplemented lep tin accelerated normal wound-healing conditions in wild-type mice. As asses sed by immunohistochemistry, proliferating keratinocytes located at the wou nd margins specifically expressed the leptin-receptor subtype ObRb during r epair. Additionally, leptin mediated a mitogenic stimulus to the human kera tinocyte cell line HaCaT and human primary keratinocytes in vitro. Therefor e, leptin might represent an effective novel therapeutic factor to improve impaired wound-healing conditions.