Leptin promotes wound healing in the skin

PLoS One. 2015 Mar 23;10(3):e0121242. doi: 10.1371/journal.pone.0121242. eCollection 2015.

Abstract

Introduction: Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.

Methods: Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R) in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.

Results: Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.

Conclusion: Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Angiogenesis Inducing Agents / administration & dosage*
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Humans
  • Keratinocytes / drug effects
  • Leptin / administration & dosage*
  • Leptin / pharmacology
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Receptors, Leptin / metabolism
  • Skin / injuries*
  • Skin / metabolism
  • Wound Healing / drug effects*

Substances

  • Angiogenesis Inducing Agents
  • LEPR protein, human
  • Leptin
  • Receptors, Leptin
  • leptin receptor, mouse

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research (No. 24593015, 24593016, 24659905, 24792262, 25861984, and 25293415) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.