A dipeptidyl peptidase-4 inhibitor promotes wound healing in normoglycemic mice by modulating keratinocyte activity

Exp Dermatol. 2018 Oct;27(10):1134-1141. doi: 10.1111/exd.13751. Epub 2018 Aug 14.

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a well-known and novel class of oral antihyperglycaemic drugs. DPP-4 inhibition facilitates ulcer healing in patients with diabetes. However, the actual mechanisms, which are independent of lower blood glucose levels, are still unknown. Therefore, the aim of this study was to analyse the effect of the DPP-4 inhibitor sitagliptin on wound healing through a glucose-independent pathway. In this study, DPP-4 inhibitors facilitate keratinocyte differentiation and the proliferation, increase blood flow in the cutaneous of wounds in healthy C57BL/6 mice. Additionally, the administration of the DPP-4 inhibitor ameliorates wound healing and enhances adiponectin expression in healthy C57BL/6 mice. Taken together, our results reveal a protective role for the DPP-4 inhibitor sitagliptin in wound healing by regulating adiponectin and phospho-eNOS levels in keratinocytes. Based on these results, the DPP-4 inhibitor may have therapeutic potential for healing wounds through a diabetes-independent mechanism.

Keywords: dipeptidyl peptidase-4; keratinocyte; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / metabolism*
  • Animals
  • Blood-Brain Barrier / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Dipeptidyl Peptidase 4 / blood
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Glucagon-Like Peptide 1 / blood
  • Keratinocytes / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation
  • Re-Epithelialization / drug effects*
  • Regional Blood Flow / drug effects*
  • Sitagliptin Phosphate / pharmacology*
  • Skin / blood supply
  • Skin / injuries
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Substances

  • Adiponectin
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide 1
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Dipeptidyl Peptidase 4
  • Dpp4 protein, mouse
  • Sitagliptin Phosphate