Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair
Stefan Frank, … , Nicole Kolb, Josef Pfeilschifter
Stefan Frank, … , Nicole Kolb, Josef Pfeilschifter
Published August 15, 2000
Citation Information: J Clin Invest. 2000;106(4):501-509. https://doi.org/10.1172/JCI9148.
View: Text | PDF
Article

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

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Effect of leptin on epithelial proliferation and localization of leptin-...
Effect of leptin on epithelial proliferation and localization of leptin-receptor subtypes in the skin. (a and d) Hematoxylin/eosin-stained frozen sections from 10-day wounds isolated from the same C57BL/6J-ob/ob individual that had been treated topically with 1 μg leptin/20 μL PBS twice a day on the left-side wounds (a) or PBS only on the right-side wounds (d), respectively. Arrows indicate the leading edge of the migrating epithelium. (b and e) Frozen sections from 5-day wounds isolated from leptin-treated (intraperitoneally) (b) or PBS-injected (e) C57BL/6J-ob/ob mice were incubated with a monospecific, polyclonal Ab directed against murine Ki67. (c) Frozen section from a 13-day wound isolated from a leptin-treated (intraperitoneally) mouse. The section was incubated with a monospecific polyclonal Ab against the ObRb-receptor subtype. (f) Frozen section from a 7-day wound isolated from a PBS-treated (intraperitoneally) mouse. The section was incubated with a monospecific polyclonal Ab against the ObRb-receptor subtype. Note that the epithelium did not extend into the granulation tissue (compare to b, epithelium of leptin-treated mouse, 5 days). (g) Frozen section from a 13-day wound isolated from a wild-type mouse (BALB/c). The section was incubated with a monospecific polyclonal Ab recognizing the ObRb- and ObRa-receptor subtypes. Sections were stained with the avidin-biotin-peroxidase complex system using 3-amino-9-ethylcarbazole as a chromogenic substrate (b, c, e, f, g). Nuclei were counterstained with hematoxylin. Strongly immunopositive signals within the sections are indicated with arrows. e, epithelium; g, granulation tissue; he, hyperproliferative epithelium; s, scab.