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.
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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

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Regulation of leptin-receptor expression during wound healing in Balb/c ...
Regulation of leptin-receptor expression during wound healing in Balb/c (wt) and C57BL/6J-ob/ob mice. (a) C57BL/6J mice were intraperitoneally treated with leptin as described in Methods. Total cellular RNA (20 μg) from nonwounded and wounded back skin of C57BL/6J-ob/ob mice treated with leptin as indicated was analyzed by RNase protection assay with an RNA hybridization probe complementary to ObRb and ObRa leptin–receptor splice variants. For every experimental time point, three wounds each from three animals (total: n = 9 wounds) were pooled for analysis. The time after injury is indicated for each lane. Control skin refers to nonwounded skin. Hybridization probe (1000 counts/min) was added to the lane labeled probe. Expression of GAPDH mRNA is shown as a loading control in the bottom panel. (b) Total protein (50 μg) from lysates of nonwounded and wounded back skin (day 1, 3, 5, 7, and 13 after injury, indicated for each lane) of C57BL/6J-ob/ob mice treated with leptin or PBS (used as control) as indicated were analyzed by immunoblotting for the presence of leptin-receptor subtype proteins ObRa and ObRb. Two wounds from the backs of three animals (n = 6) were excised for each experimental time point and used for protein isolation. Leptin-receptor subtypes ObRa and ObRb are indicated by arrowheads.