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

Area of Science:

• Biomedical Science
• Wound Healing Research
• Diabetes Complications

Background:

• Diabetic foot ulcer (DFU) presents significant challenges due to impaired healing and inflammation.
• Thrombospondin 1 (TSP1) and Thrombospondin 4 (TSP4) are crucial extracellular matrix proteins in wound repair.
• Superoxide dismutase 3 (SOD3) also plays a role in tissue health.

Purpose of the Study:

• To evaluate TSP1, TSP4, and SOD3 expression levels in DFU tissues.
• To identify potential therapeutic agents that can modulate these protein levels for improved DFU treatment.

Main Methods:

• Real-time PCR and immunohistochemistry were used to assess TSP1, TSP4, and SOD3 expression in DFU samples.
• Pharmacological repositioning was employed to screen for drugs that influence TSP4 levels.

Main Results:

• DFU tissues exhibited significantly reduced TSP4 expression, confirmed at both mRNA and protein levels.
• TSP1 expression showed no significant alterations in DFU tissues.
• SOD3 mRNA levels were decreased in diabetic patients, but protein levels remained unchanged.
• Riboflavin, desloratadine, and chenodeoxycholic acid were identified as drugs that selectively increase TSP4 expression.

Conclusions:

• Reduced TSP4 expression is a key feature of diabetic foot ulcers.
• Riboflavin, desloratadine, and chenodeoxycholic acid show promise in promoting DFU healing by upregulating TSP4.
• These drugs may enhance tissue remodeling and angiogenesis, offering novel therapeutic strategies for DFU.