Multifaceted Roles of Ferroptosis in Lung Diseases

Abstract

Ferroptosis is a distinct type of programmed cell death (PCD) that depends on iron and is characterized by the accumulation of intracellular iron, exhaustion of glutathione, deactivation of glutathione peroxidase, and promotion of lipid peroxidation. Recently, accumulated investigations have demonstrated that ferroptosis is strongly correlated with the initiation and development of many lung diseases. In this review, we summarized the contribution of ferroptosis to the pathologic process of lung diseases, namely, obstructive lung diseases (chronic obstructive pulmonary disease, asthma, and cystic fibrosis), interstitial lung diseases (pulmonary fibrosis of different causes), pulmonary diseases of vascular origin (ischemia-reperfusion injury and pulmonary hypertension), pulmonary infections (bacteria, viruses, and fungi), acute lung injury, acute respiratory distress syndrome, obstructive sleep apnea, pulmonary alveolar proteinosis, and lung cancer. We also discussed the therapeutic potential of targeting ferroptosis for these lung diseases.

Scutellarein alleviates chronic obstructive pulmonary disease through inhibition of ferroptosis by chelating iron and interacting with arachidonate 15‐lipoxygenase

“…Ferroptosis, a new type of necrotic cell death, is characterized by an iron‐dependent accumulation of lipid peroxides (LPOs) and redox imbalance (Lei et al, 2019, 2020; Yan et al, 2021). Recent studies have demonstrated that ferroptosis of respiratory epithelial cells is implicated in the pathogenesis of COPD (Li et al, 2022; Yang et al, 2022; Yoshida et al, 2019). Several etiological agents of COPD such as cigarette smoke (CS) can induce the accumulation of labile iron via induction of ferritinophagy, thereby resulting in an iron‐dependent production of LPOs via Fenton reaction (Yoshida et al, 2019).…”

Ferroptosis—A New Dawn in the Treatment of Organ Ischemia–Reperfusion Injury

“…Subsequently, the activation of pSTAT3 inhibits OGD/R-induced ferroptotic damage in MLE12 cells and pathological processes associated with ALI by modulating SLC7A11 [ 156 ]. Irisin, a muscle-derived myokine with potent protective effects, inhibits ferroptosis in pulmonary IRI both in vitro and in vivo [ 157 ]. Consistent with the action of Fer-1, inhibition of ferroptosis in pulmonary IRI by irisin was manifested by lower ROS, MDA, and Fe 2+ levels and increased the expression levels of GPX4, which was achieved by promoting NRF2/HO-1 signaling.…”

New molecular insights into ferroptosis in lung adenocarcinoma progression and pharmacological compounds for targeted therapy

“…[10][11][12] The involvement of ferroptosis has been found in many pathological conditions of the lung, such as acute lung injury, pulmonary fibrosis, asthma, chronic obstructive pulmonary disease, pulmonary hypertension and tuberculosis. 13 Several ferroptosis regulators, including iron homeostasis regulators and lipid peroxidation inhibitors, have been shown to have therapeutic effects on acute lung injury. 14 A large amount of iron is reported to be deposited in the lung tissue of patients with pulmonary fibrosis, which induces iron death and promotes the development of pulmonary fibrosis.…”

“…Ferroptosis, comprising a form of programmed cell death that was first reported in 2012, is characterized by the overwhelming, iron‐dependent accumulation of lethal lipid reactive oxygen species 10–12 . The involvement of ferroptosis has been found in many pathological conditions of the lung, such as acute lung injury, pulmonary fibrosis, asthma, chronic obstructive pulmonary disease, pulmonary hypertension and tuberculosis 13 . Several ferroptosis regulators, including iron homeostasis regulators and lipid peroxidation inhibitors, have been shown to have therapeutic effects on acute lung injury 14 .…”