Cuproptosis-related gene TMPO affects the healing of diabetic foot ulcers through TGF-β/Smad signaling pathway

Cuproptosis, a form of programmed cell death distinct from apoptosis, is associated with oxidative stress and inflammation. However, its role in diabetic foot ulcers (DFUs) remains unclear. In this study, we utilized the GEO database and employed differential expression analysis and machine learning approaches to identify the cuproptosis-related gene Thymopoietin (TMPO). <i>In vitro</i> cellular experiments demonstrated that TMPO expression was upregulated under high glucose conditions, and its knockdown promoted cell proliferation and migration while activating the TGF-β/Smad signaling pathway. <i>In vivo</i> animal experiments revealed that TMPO knockdown reduced inflammation, improved tissue regeneration, enhanced microvascular and collagen formation, and facilitated wound healing. Our study established a connection between DFU and cuproptosis, identifying that TMPO regulates diabetic wound healing through the TGF-β/Smad signaling pathway. These findings provide new insights and potential strategies for DFU treatment.