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

J Clin Invest. 2000 Aug;106(4):501-9. doi: 10.1172/JCI9148.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Carrier Proteins / genetics
  • Cell Division / drug effects
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Epithelium / drug effects
  • Epithelium / physiology
  • Female
  • Gene Expression
  • Humans
  • Injections, Intraperitoneal
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Leptin / administration & dosage
  • Leptin / genetics
  • Leptin / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Obese
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface*
  • Receptors, Leptin
  • STAT3 Transcription Factor
  • Skin / drug effects
  • Skin / injuries*
  • Skin / physiopathology
  • Trans-Activators / metabolism
  • Wound Healing / drug effects
  • Wound Healing / genetics
  • Wound Healing / physiology*

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Leptin
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Leptin
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Trans-Activators
  • leptin receptor, human
  • leptin receptor, mouse