Role of Ferroptosis on Lung Epithelial Cells in Disease Progression and Treatment: A Review.

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.