Optimizing thrombospondin function through repositioning: Implications for injury and diabetic foot ulcer management

Diabetic foot ulcer (DFU) is a common and challenging complication of diabetes, characterized by impaired wound healing, chronic inflammation, poor tissue remodeling, and chronic inflammation. Thrombospondin 1 (TSP1) and thrombospondin 4 (TSP4) are key extracellular matrix proteins involved in wound healing. This study aimed to assess the levels and propose inducers of TSP1, TSP4, and SOD3 in diabetic foot ulcer. In this study, we first evaluated the expression of TSP1, TSP4, and superoxide dismutase 3 (SOD3) in DFU tissues using real-time PCR and immunohistochemistry. In DFU tissues using real-time PCR we found that TSP-4 expression was significantly reduced and confirmed by immunohistochemistry. TSP1 expression did not show similar alterations. Additionally, while SOD3 expression was decreased at the mRNA level in the diabetic population, no changes were observed in the protein levels by immunohistochemistry. To explore potential therapeutic approaches, we performed pharmacological repositioning and identified three drugs riboflavin, desloratadine, and chenodeoxycholic acid that selectively increased TSP-4 expression. These findings suggest that riboflavin, desloratadine, and chenodeoxycholic acid may promote wound healing in DFU by specifically upregulating TSP4, potentially enhancing tissue remodeling and angiogenesis.