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 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.
Frank
S
S
Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany. S.Frank@em.uni-frankfurt.de
Stallmeyer
B
B
Kämpfer
H
H
Kolb
N
N
Pfeilschifter
J
J
D000287:Administration, Topical; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007274:Injections, Intraperitoneal; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008820:Mice, Obese; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D012867:Skin / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology; D015534:Trans-Activators / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C515448:LEPR protein, human; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C515447:leptin receptor, mouse