TFAP2A-Induced M2 Macrophage Polarization Enhances Wound Healing in DFUs

With the increase in diabetes, diabetic foot ulcers (DFUs) have become a global health problem, significantly impacting the quality of life and healthcare systems. Among the various subtypes of immune cells, M2-polarized macrophages play a crucial role in tissue repair and resolution of inflammation. This study comprehensively investigates the functionality of the TFAP2A-LIFR-Hippo-YAP signaling axis in regulating the M2 polarization of macrophages and its critical role in the wound healing of DFUs, using single-cell transcriptomic sequencing and bulk transcriptomic sequencing. Through scRNA-seq analysis, nine major immune cell subtypes, with macrophages being the key cells, were identified in DFU samples. TFAP2A, a key gene that influences macrophage function in DFUs, upregulates LIFR expression and activates the Hippo-YAP signaling pathway, inducing M2 polarization of macrophages and improving endothelial dysfunction. Additionally, the TFAP2A-LIFR-Hippo-YAP signaling axis promotes wound healing in DFU mice by inducing M2 polarization of macrophages.