The interplay of ferroptosis and oxidative stress in pulmonary fibrosis: from mechanisms to treatment.

Pulmonary fibrosis (PF) is a progressive and devastating interstitial lung disease characterized by the dynamic imbalance of multiple cell types and signaling pathways. In recent years, ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, has been recognized as playing a significant role in the progression of pulmonary fibrosis due to its central role in oxidative stress, metabolic dysfunction, and disruption of barrier integrity. Existing studies have elucidated the core signaling pathways, key molecules, and potential roles of ferroptosis in PF progression, highlighting the synergistic pathogenic effects of iron homeostasis disruption and lipid peroxidation. Despite its established role in fibrosis, a comprehensive analysis of the cell-type-specific mechanisms of ferroptosis within pulmonary cell populations remains lacking. Furthermore, several small-molecule inhibitors targeting ferroptosis have demonstrated promising anti-fibrotic effects in animal models, yet their tissue-specificity, safety profiles, and clinical feasibility warrant further investigation. This review systematically summarizes the cell-type-specific roles of ferroptosis in PF, delineates the key molecular mechanisms and potential druggable targets involved, and underscores the potential of ferroptosis as a critical regulatory node at the intersection of metabolism and cell fate. By bridging the understanding of metabolic regulation and cell death processes, ferroptosis holds promise for providing novel mechanistic insights and informing precise therapeutic strategies for pulmonary fibrosis.