Annexin A1‐derived peptide Ac2‐26 facilitates wound healing in diabetic mice.

Impaired wound healing is a common complication of diabetes. In diabetic wounds, macrophages present dysfunctional efferocytosis and abnormal phenotypes, which could result in excessive neutrophil accumulation and prolonged inflammation, thereby eventually hindering wound repair. ANXA1 N‐terminal peptide Ac2‐26 exhibits a high potential in mitigating inflammation and improving repair; however, its efficacy in diabetic wound repair remains unclear. In this study, a cutaneous excisional wound model was built in genetically diabetic mice. Ac2‐26 or a vehicle solution was employed locally in wound sites. Subsequently, wound zones were measured and sampled at different time intervals post‐wounding. Using hematoxylin‐eosin and Masson's trichrome staining, we observed the histopathological variations and collagen deposition in wound samples. Based on immunohistochemistry and immunofluorescence, the numbers of neutrophils, macrophages, and CD206‐positive macrophages in the wound samples were determined. Cytokine expression in wound samples was studied by immunoblot assay. Results showed that Ac2‐26 treatment could facilitate diabetic wound closure, down‐regulate the number of neutrophils, and improve angiogenesis and collagen deposition. In addition, Ac2‐26 application expedited macrophage recruitment and up‐regulated the percentage of macrophages expressing CD206, which is a marker for M2 macrophages. Moreover, Ac2‐26 inhibited the expressions of TNF‐α and IL‐6 and up‐regulated the expressions of IL‐10, TGF‐β, and VEGFA during diabetic wound healing. Hence, based on the aforementioned findings, Ac2‐26 application in diabetic wounds could exert anti‐inflammatory and pro‐repair effects by reducing neutrophil accumulation and facilitating M2 macrophage development. [ABSTRACT FROM AUTHOR]