TGF-β1 promotes wound healing after ionizing radiation through the TGFβ-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 TGFβ 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 TGFβ-SMAD pathway exhibited temporal changes during the wound healing process, while pre-treatment with TGFβ1 significantly promotes the healing of IR-induced wounds. Innovation: TGF-β1 activated the TGFβ-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 TGFβ-Smad pathway. However, the external application of TGFβ1 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. 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.