Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair
Stefan Frank, Birgit Stallmeyer, Heiko Kämpfer, Nicole Kolb, Josef Pfeilschifter
Stefan Frank, Birgit Stallmeyer, Heiko Kämpfer, Nicole Kolb, Josef Pfeilschifter
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Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair

Abstract

Wound-healing disorders are a therapeutic problem of extensive clinical importance. Leptin-deficient ob/ob mice are characterized by a severely delayed wound healing that has been explained by the mild diabetic phenotype of these animals. Here we demonstrate that systemically and topically supplemented leptin improved re-epithelialization of wounds in ob/ob mice. Leptin completely reversed the atrophied morphology of the migrating epithelial tongue observed at the wound margins of leptin-deficient animals into a well-organized hyperproliferative epithelium. Moreover, topically supplemented leptin accelerated normal wound-healing conditions in wild-type mice. As assessed by immunohistochemistry, proliferating keratinocytes located at the wound margins specifically expressed the leptin-receptor subtype ObRb during repair. Additionally, leptin mediated a mitogenic stimulus to the human keratinocyte cell line HaCaT and human primary keratinocytes in vitro. Therefore, leptin might represent an effective novel therapeutic factor to improve impaired wound-healing conditions.

Authors

Stefan Frank, Birgit Stallmeyer, Heiko Kämpfer, Nicole Kolb, Josef Pfeilschifter

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Effect of intraperitoneally and topically supplemented leptin on blood g...
Effect of intraperitoneally and topically supplemented leptin on blood glucose level, body weight, and wound healing in ob/ob mice. C57BL/6J-ob/ob mice were treated with leptin intraperitoneally (i.p.) or topically (top) as described in Methods. PBS-treated ob/ob mice were used as a control. (a and b) Blood glucose levels and body weight were determined for intraperitoneally injected (a) or topically treated (b) animals at the indicated experimental time points. Three animals (n = 3) were analyzed at every experimental time point. Data are expressed as milligrams per deciliter (for blood glucose levels) or grams (for body weight). Mean changes ± SD in blood glucose levels, or body weight, respectively, are shown. AP < 0.05; BP < 0.01; NS, not significant compared with the conditions as indicated with the brackets. (c) Thirteen-day wounds after intraperitoneal (i.p.) treatment of animals with 5 μg leptin/g of body weight (+leptin/i.p.) or PBS (+PBS/i.p.). (d) Back skin of representative C57BL/6J-ob/ob mice topically treated with 1 μg leptin in 20 μL PBS twice a day (+leptin/top.) or PBS (+PBS/top.) at day 10 after wounding. The bottom panels demonstrate the same wounds in higher magnification.