Yin Xi, Hou Xiaohui, Feng Jian
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.
Department of Clinical Laboratory, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, Jiangsu, China.
Med Sci Monit. 2025 Sep 24;31:e948226. doi: 10.12659/MSM.948226.
Lung epithelial cells, including bronchial and alveolar epithelial cells, serve as the frontline barrier of the respiratory tract and play essential roles in maintaining pulmonary homeostasis and immune defense. Dysfunction of these epithelial cells contributes significantly to the development and progression of various lung diseases. Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation and glutathione depletion, has emerged as a key mechanism in pulmonary pathology. It plays distinct roles in benign and malignant lung conditions. In chronic obstructive pulmonary disease and asthma, ferroptosis promotes bronchial epithelial damage, oxidative stress, and persistent inflammation. Pathogens, such as Pseudomonas aeruginosa and SARS-CoV-2, induce ferroptosis to exacerbate epithelial injury. In pulmonary fibrosis, ferroptosis of alveolar epithelial cells contributes to tissue remodeling through oxidative stress and epithelial-mesenchymal transition. In lung cancer, ferroptosis affects carcinogenesis, therapy resistance, and response to radiotherapy. Emerging therapeutic strategies target ferroptosis using inhibitors, such as ferrostatin-1 and deferoxamine, or inducers, such as erastin and sulfasalazine, to modulate cell fate in a disease-specific manner. Natural compounds, such as curcumin, resveratrol, and nanomaterials, further enhance ferroptosis-based treatment potential. Ferroptosis thus offers a novel perspective on lung disease mechanisms and treatment. This article aims to review the role of epithelial cell ferroptosis in benign and malignant lung diseases.
肺上皮细胞，包括支气管和肺泡上皮细胞，是呼吸道的一线屏障，在维持肺部稳态和免疫防御中发挥着重要作用。这些上皮细胞的功能障碍在各种肺部疾病的发生和发展中起着重要作用。铁死亡是一种铁依赖性的程序性细胞死亡形式，其特征是脂质过氧化和谷胱甘肽耗竭，已成为肺部病理学的关键机制。它在良性和恶性肺部疾病中发挥着不同的作用。在慢性阻塞性肺疾病和哮喘中，铁死亡会促进支气管上皮损伤、氧化应激和持续性炎症。铜绿假单胞菌和严重急性呼吸综合征冠状病毒2等病原体可诱导铁死亡，从而加剧上皮损伤。在肺纤维化中，肺泡上皮细胞的铁死亡通过氧化应激和上皮-间质转化促进组织重塑。在肺癌中，铁死亡影响肿瘤发生、治疗耐药性和对放疗的反应。新兴的治疗策略使用铁死亡抑制剂（如铁抑素-1和去铁胺）或诱导剂（如艾拉司丁和柳氮磺胺吡啶）以疾病特异性方式调节细胞命运。姜黄素、白藜芦醇等天然化合物以及纳米材料进一步增强了基于铁死亡的治疗潜力。因此，铁死亡为肺部疾病的机制和治疗提供了一个新的视角。本文旨在综述上皮细胞铁死亡在良性和恶性肺部疾病中的作用。
