Expression of PROS1 in Negative Pressure Treatment of Diabetic Foot Ulcers and its Effect on Angiogenesis.

OBJECTIVE: This study aimed to investigate the role of protein S (PROS1) in the pro-healing effects of negative pressure wound therapy (NPWT) on diabetic foot ulcers (DFU). METHODS: Serum and granulation tissue samples were collected from patients with DFU and non-diabetic skin ulcer control (SUC) subjects. PROS1 expression levels were measured before and after NPWT. For in vitro functional verification, human umbilical vein endothelial cells (HUVECs) were cultured under normal or high-glucose (HG) conditions. Experiments were performed to explore the regulatory role of PROS1 in endothelial proliferation, tube formation, and apoptosis in both PROS1 knockdown and overexpression in HG-cultured HUVECs. RESULTS: Baseline tissue PROS1 expression was lower in the DFU group compared to the SUC group. PROS1 mRNA and protein levels were significantly upregulated in the granulation tissue of both groups at Post-NPWT, accompanied by increased VEGF and CD31 expression and improved histological angiogenesis. In vitro, PROS1 knockdown restrained proliferation and tube formation but induced apoptosis of HUVECs under both normal and HG conditions. Conversely, PROS1 overexpression rescued HG-induced endothelial dysfunction by restoring cell proliferation, angiogenic capacity, and inhibiting excessive apoptosis. Importantly, the magnitude of the PROS1 increase in tissue following NPWT was positively correlated with the 4-week wound healing rate. In patients with DFU, changes in serum PROS1 were negatively correlated with C-reactive protein (CRP), an inflammatory marker. CONCLUSION: Our findings demonstrate that NPWT promotes DFU healing by upregulating PROS1 expression, which in turn enhances angiogenesis and modulates inflammation. These results establish PROS1 as a promising therapeutic target and a predictive biomarker for wound healing in DFUs.