TGF-ß1 promotes wound healing after ionizing radiation through the TGFß-SMAD canonical signaling pathway
Objective: Ionizing radiation (IR) therapy, commonly used in cancer treatment, has detrimental effects on the skin. When combined with surgical resection, IR leads to persistent wounds and forms a significant side effect, making wound healing difficult. This study aimed to understand the mechanisms underlying IR-induced wound damage and develop treatment methods. Approach: A mouse model of IR was created by exposing mice to 7Gy of radiation after skin excision. The temporal changes of epidermal stem cells (EPSCs) and wound healing were examined. RNA-seq analysis was performed on skin tissues to investigate regulatory mechanisms during the healing process. Topical application of TGFß was used to assess its impact on wound healing. Results: Mice in the IR group exhibited prolonged wound healing time, and the healing rate was significantly reduced. IR exposure decreased Ki67+/K14+ cells (proliferating EPSCs), reduced the expression levels of K14 and K15. The RNA-seq results revealed a significant decrease in epidermal stem cell-related genes following IR. Additionally, the TGFß-SMAD pathway exhibited temporal changes during the wound healing process, while pre-treatment with TGFß1 significantly promotes the healing of IR-induced wounds. Innovation: TGF-ß1 activated the TGFß-SMAD pathway and promotes wound healing after ionizing radiation. Conclusions: These findings indicate that IR diminishes the population of epidermal stem cells (EPSCs), thereby impeding the healing process by disrupting the TGFß-Smad pathway. However, the external application of TGFß1 to the wound area effectively improves IR-induced skin damage and exhibits promising therapeutic effects. These findings provide intervention targets and agents for the clinical applications. Overall design: To investigate the molecules involved in wound healing after IR, we employed RNA-seq analysis to examine the gene expression changes in the control and IR groups at 3, 6, 9 day post-injury.