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A double-edged sword: iron regulation in alveolar lung epithelial repair
Ugonna Mbaekwe, Sarah Kenny, Suzanne M. Cloonan, Corrine R. Kliment
Ugonna Mbaekwe, Sarah Kenny, Suzanne M. Cloonan, Corrine R. Kliment
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Review

A double-edged sword: iron regulation in alveolar lung epithelial repair

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Abstract

The oxygen-rich milieu of the lungs necessitates precise iron homeostasis and regulation, processes that are fundamental to pulmonary physiology but often receive limited attention. However, in recent years, dysregulation of iron homeostasis has been linked to numerous acute and chronic respiratory diseases. Here, we comprehensively evaluate the mechanisms governing iron homeostasis in the alveolar epithelium of the lung and examine how iron dysregulation contributes to impaired alveolar epithelial repair in respiratory disease. This Review focuses on the effects of iron on alveolar epithelial cell homeostasis and repair and disease pathogenesis. There will be a focus on emerging interventions designed to reestablish iron homeostasis and their potential therapeutic implications related to enhancing lung repair and limiting the progression of lung disease.

Authors

Ugonna Mbaekwe, Sarah Kenny, Suzanne M. Cloonan, Corrine R. Kliment

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Figure 3

Lung iron homeostasis.

Options: View larger image (or click on image) Download as PowerPoint
Lung iron homeostasis.
A schematic illustrating lung iron sources and re...
A schematic illustrating lung iron sources and regulation (top) and how iron dysregulation triggers ferroptosis (bottom) in lung epithelial cells affected by disease. The lung depends on endogenous sources, like cellular recycling, and exogenous sources, such as particulate matter, which increases oxidative stress and inflammation. Excess iron results in ROS, lipid peroxidation, and ferroptosis when antioxidants are overwhelmed. Created in BioRender.

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