Stimulation of cutaneous wound healing by an FPR2-specific peptide agonist WKYMVm

ABSTRACT Diabetes is one of the most common human diseases and 15% of the 200 million diabetics worldwide suffer from diabetic wounds. Development of new therapeutic agents is needed for treatment of diabetic wounds. Wound healing is mediated by multiple steps, including inflammation, epithelialization, neoangiogenesis, and granulation. Formyl peptide receptor 2 has been known to stimulate angiogenesis, which is essential for tissue repair and cutaneous wound healing. In this study, we explored the therapeutic effects of WKYMVm (Trp‐Lys‐Tyr‐Met‐Val‐D‐Met‐NH2), a synthetic peptide agonist of formyl peptide receptor 2, on cutaneous wounds in streptozotocin‐induced diabetic rats. Topical application of WKYMVm onto cutaneous wounds stimulated formation of von Willebrand factor‐positive capillary and α‐smooth muscle actin‐positive arteriole with a maximal stimulation on day 6, suggesting WKYMVm‐stimulated angiogenesis. Infiltration of immune cells could be detected on early phase during wound healing and WKYMVm treatment acutely augmented infiltration of CD68‐positive macrophages. In addition, reepithelialization and granulation tissue formation were accelerated by treatment with WKYMVm. These results suggest that WKYMVm has therapeutic effects on diabetic wounds by stimulating angiogenesis and infiltration of immune cells.