Leptin promotes wound healing in the oral mucosa

PLoS One. 2014 Jul 17;9(7):e101984. doi: 10.1371/journal.pone.0101984. eCollection 2014.

Abstract

Introduction: Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa.

Methods: Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively.

Results: Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin.

Conclusion: Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration 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 oral mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adult
  • Animals
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Endothelial Cells / physiology
  • Epidermal Growth Factor / biosynthesis
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology*
  • Fibroblast Growth Factor 7 / biosynthesis
  • Humans
  • Leptin / therapeutic use*
  • Male
  • Mouth Mucosa / physiology*
  • Rabbits
  • Receptors, Leptin / biosynthesis
  • Wound Healing / drug effects*
  • Wound Healing / physiology*

Substances

  • FGF7 protein, human
  • Leptin
  • Receptors, Leptin
  • Fibroblast Growth Factor 7
  • Epidermal Growth Factor

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research (No. 24593016, 25293415, 24659905, 23792392, and 24593015) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.