ALDH2 attenuates radiation-induced lung injury by inhibiting ROS and epithelial-mesenchymal transition mediated by the TGF-β1/Smad pathway.

Abstract

Radiation-induced lung injury is a significant complication of thoracic malignant tumor radiotherapy, yet effective treatments remain scarce. Aldehyde dehydrogenase 2 (ALDH2) possesses antioxidant and anti-inflammatory properties, but its specific role in radiation-induced lung injury is not well understood. This study aimed to investigate the impact of ALDH2 on radiation-induced lung injury and elucidate the underlying mechanisms. Through analysis of radiation-induced lung injury datasets, intervention with ALDH2 agonists and inhibitors in an in vivo radiation-induced lung injury model, and establishment of an in vitro radiation-induced lung injury model using A549 stable cells with varying ALDH2 expressions, we discovered that ALDH2 expression is reduced in radiation-induced lung injury. Enrichment analysis suggested that ALDH2 may mitigate radiation-induced lung injury by modulating oxidative stress and inflammation levels. Additionally, single-cell data analysis reveals that ALDH2 is primarily localized in myeloid macrophages within the lungs, with its expression also being reduced in lung cancer patients. Subsequent examination of mouse pathological sections, reactive oxygen species (ROS), and inflammatory factor levels confirmed that ALDH2 can lessen radiation-induced lung injury by suppressing ROS and inflammatory factors. Both in vivo and in vitro Western blot analysis further validated that ALDH2 can attenuate epithelial-mesenchymal transition and inhibit the TGF-β1/Smad pathway. Therefore, ALDH2 shows promise in reducing radiation-induced lung injury by inhibiting ROS and TGF-mediated epithelial-mesenchymal transition, making it a potential target for the treatment of radiation-induced lung injury.