Exogenous Irisin Repair Skin Wounds in Streptozotocin-induced Diabetic Mice Through the AMPK–NF-κB Signaling Pathway

Background: Diabetic foot ulcer, a severe complication occurring in diabetic patients, lacks effective remedies at present. Objectives: The objective of this research is to investigate the impacts of exogenous irisin on diabetic wounds in mice and explore the associated mechanisms. Materials and Methods: An animal model was constructed by administration of streptozotocin (STZ) (50 mg/kg) in mice to simulate a diabetic condition. A full-thickness excisional wound was produced on the dorsal skin of the mice to create a wound for the observation of the wound healing process. Cutaneous administration of 0.1 mL of exogenous irisin solution (1 µg/mL and 3 µg/mL) was applied to the injured tissue to assess the impact of exogenous irisin on the wound. Hematoxylin and eosin (H&E) staining assay was applied to evaluate histological changes in the skin tissue. The expression levels of endogenous irisin, adenosine 5′-monophosphate-activated protein kinase (AMPK), nuclear factor kappa B (NF-κB), and inflammatory factors in the skin tissue of the mice were measured by enzyme-linked immunosorbent assay (ELISA). Results: The results showed that irisin levels are positively correlated with the progress of wound healing. The STZ mice exhibited decreased pAMPK, increased NF-κB, and increased inflammatory cytokines. Exogenous irisin treatment restored these abnormal expressions in STZ mice. However, co-treatment with the AMPK inhibitor, Compound C, abolished exogenous irisin’s function of promoting wound healing and relieving inflammation. Conclusion: Taken together, exogenous irisin possesses a therapeutic effect on skin wounds in STZ-induced diabetic mice, which is related to the regulation of inflammatory factors mediated by the AMPK–NF-κB pathway.