Li Enping, Huang Jianliang, Huang Jiale, Zhang Fuying, Li Chengyou, Xia Mingkai, Li Zhuo, Peng Bo, Liu Ying, Ma Jinan, Lei Mingsheng
Department of Pulmonary and Critical Care Medicine, Zhangjiajie Hospital Affiliated to Hunan Normal University, Zhangjiajie, 427000, Hunan, China; Biomedical Research Institute, Zhangjiajie College, Zhangjiajie, 427000, Hunan, China.
Department of Pulmonary and Critical Care Medicine, Zhangjiajie Hospital Affiliated to Hunan Normal University, Zhangjiajie, 427000, Hunan, China.
Pulm Pharmacol Ther. 2024 Dec;87:102334. doi: 10.1016/j.pupt.2024.102334. Epub 2024 Nov 26.
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.
放射性肺损伤是胸部恶性肿瘤放疗的一种重要并发症，但有效的治疗方法仍然匮乏。乙醛脱氢酶2（ALDH2）具有抗氧化和抗炎特性，但其在放射性肺损伤中的具体作用尚不清楚。本研究旨在探讨ALDH2对放射性肺损伤的影响，并阐明其潜在机制。通过分析放射性肺损伤数据集、在体内放射性肺损伤模型中使用ALDH2激动剂和抑制剂进行干预，以及利用具有不同ALDH2表达的A549稳定细胞建立体外放射性肺损伤模型，我们发现放射性肺损伤中ALDH2表达降低。富集分析表明，ALDH2可能通过调节氧化应激和炎症水平来减轻放射性肺损伤。此外，单细胞数据分析显示，ALDH2主要定位于肺内的髓样巨噬细胞，肺癌患者中其表达也降低。随后对小鼠病理切片、活性氧（ROS）和炎症因子水平的检测证实，ALDH2可通过抑制ROS和炎症因子来减轻放射性肺损伤。体内和体外的蛋白质印迹分析进一步验证，ALDH2可减弱上皮-间质转化并抑制TGF-β1/Smad信号通路。因此，ALDH2有望通过抑制ROS和TGF介导的上皮-间质转化来减轻放射性肺损伤，使其成为治疗放射性肺损伤的潜在靶点。
