CuATSM Enhances Wound Repair Without Scarring via Hippo/YAP Signalling Pathway to Reduce Ferroptosis and Macrophage Polarisation

Abstract

Skin wound healing is a complex biological process involving haemostasis, inflammation, proliferation/repair and remodelling. However, skin scarring, as one of the important stages in the healing process, can adversely affect the structure and function of related organs. Currently, effective treatments to address such scars remain insufficient. In this study, we established a full-thickness skin excision wound model using male ICR mice, which were randomly divided into a Control group and a CuATSM group. The CuATSM group received CuATSM (30 mg/kg) via gavage, with daily treatments continuing throughout the observation period. The Control group received an equivalent volume of 0.9% sodium chloride solution. Wound healing progression was evaluated through macroscopic photography, histological analyses, Western blotting and quantification of relevant biochemical markers at different healing stages. Our study reveals that CuATSM not only promotes rapid skin wound healing but also reduces scar formation in the late healing phase. Furthermore, our findings suggest that this effect is mediated through the ferroptosis-induced Hippo/YAP signalling pathway and macrophage polarisation. These findings highlight CuATSM as a promising therapeutic candidate for achieving scarless wound repair in clinical applications.