Ophiopogonin D Reduced Ferroptosis of Skin Epithelial Cells to Thermal Injury by USP25/ TAB2

Abstract

Thermal injury are the fourth most common type of trauma globally. This study aimed to examine the impact of ophiopogonin D (OPD) on thermal injury and elucidate its underlying molecular mechanisms of Skin epithelial cells C57BL/6 mice were anaesthetized with inhaled isoflurane, pre-heated in boiling water for 10 min, was lowered onto the skin and maintained under its own weight for 5 s. USP25 mRNA and protein expression in mice model of thermal injury were down-regulation. USP25 mRNA and protein expression was suppressed in vitro model of thermal injury.Sh-USP25 exacerbated toxicity in mice model of thermal injury. In contrast, USP25 was found to reduce inflammation and ROS-induced oxidative stress in an in vitro model. Furthermore, USP25 attenuated mitochondrial damage in vitro, and increased GPX4 protein expression, thereby reducing ferroptosis in Skin epithelial cells. Mechanistically, USP25 suppressed TAB2 expression in the thermal injury model. OPD was shown to reduce ferroptosis in skin epithelial cells following thermal injury via the USP25/ TAB2. Additionally, OPD alleviated thermal injury-induced toxicity in mitigating inflammation and ROS-induced oxidative stress. In conclusion, USP25 suppressed TAB2 expression to reduce ferroptosis in Skin epithelial cells, at least in part through the inhibition of Mitochondrial damage. OPD reduces ferroptosis and overall toxicity to thermal injury by targeting inflammation and ROS-induced oxidative stress via the USP25/ TAB2 axis. These findings suggest that OPD could be a potential therapeutic compound for treating thermal injury by modulating USP25.