Targeting S100A12 to Improve Angiogenesis and Accelerate Diabetic Wound Healing

Long-term inflammation and impaired angiogenesis are thought to be the causes of delayed healing or nonhealing of diabetic wounds. Inhibiting local inflammation and promoting angiogenesis are key to accelerating diabetic wound healing. In this study, we found that the serum S100A12 concentration is significantly elevated in patients with type 2 diabetes. Exposure of stratified epidermal cells to high glucose led to increased expression of S100A12, resulting in endothelial dysfunction. The transcription factor Krüpple-like Factor 5 (KLF5) is highly expressed in the epidermis under high glucose conditions and promotes the expression of S100A12 by binding to its promoter. Blockade of the S100A12 receptor, RAGE or TLR4 alleviates high glucose-induced endothelial damage. In vivo inhibition of S100A12 significantly improved angiogenesis in diabetic rabbit wounds, thus accelerating wound healing. The above results illustrate the proinflammatory function of S100A12 in diabetic wounds and suggest that S100A12 is a potential therapeutic target for diabetic wounds.