Pro-healing impact of liraglutide on skin wounds in normoglycemic mice.

Recent studies demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RA) have promising prospects in promoting wound healing. In this study, we intend to investigate the pro-healing effect and potential molecular mechanism of topical administration of GLP-1RA liraglutide on wounds in normoglycemic mice. Two full-thickness wounds were created on the back of the C57BL/6 mice. The "lower" wounds were topically infiltrated with liraglutide every day after injury; while the "upper" wounds were infiltrated with saline solution. Wound area was measured daily during the 10-day study period. The wound tissue was stained with H&E and immunofluorescence. Western blotting was performed to detect the markers in macrophages. The results showed that topical administration of liraglutide resulted in a rapid reduction of wound size. The capillary density and the expression of vascular endothelial growth factor (VEGF)-A were significantly increased in liraglutide-treated wounds. Findings from immunofluorescence and Western blotting revealed that liraglutide promoted phenotypic polarization of macrophages from M1 to M2. We further identified that M2a macrophages predominantly presented in the early and middle stages of inflammation phase and M2d macrophages presented in the middle and late stages. Our study suggested that GLP-1RA liraglutide could promote wound healing in normoglycemic mice, which is partly attributed to the modulation of the macrophage polarization from M1 subtype to M2 subtype.