Targeting ferroptosis: A promising new therapeutic horizon for treating pneumoconiosis
A comprehensive review in Med Research highlights how inhibiting "iron-dependent" cell death can alleviate lung fibrosis caused by silica and coal dust.
image: A schematic diagram illustrating how targeting alveolar macrophages, epithelial cells, and endothelial cells by suppressing ferroptosis can alleviate pneumoconiosis. The figure highlights various therapeutic agents (such as Fer-1 and DHQ) and their mechanisms of action in preventing lung fibrosis.
Credit: Yan et al., Med Research, 2025.
Los Angeles — Pneumoconiosis, a severe occupational lung disease caused by the inhalation of inorganic dusts like silica, coal, and asbestos, remains a major global health burden. Despite its prevalence, effective treatments to reverse the progressive lung fibrosis associated with the disease are currently lacking.
In a comprehensive review published in the journal Med Research, researchers from Sichuan University and Ningxia Medical University have identified a promising therapeutic target that could change the landscape of pneumoconiosis treatment: ferroptosis.
Understanding the Mechanism
Ferroptosis is a form of regulated cell death driven by the accumulation of iron and lipid peroxides (oxidized fats) within cell membranes. Unlike other forms of cell death, ferroptosis is distinctively characterized by iron overload and the failure of the cell's antioxidant defense systems, specifically the GPX4 enzyme.
The authors of the review, led by Mengli Yan and Jing Zhang, detail how inhaled silica dust disrupts iron homeostasis in the lungs. This disruption triggers a lethal cascade in three critical lung cell types:
1. Alveolar Macrophages: The "first responders" of the immune system. When they undergo ferroptosis, they release inflammatory signals that worsen lung injury.
2. Epithelial Cells: The barrier cells of the lung. Their death prevents lung repair and promotes scarring (fibrosis).
3. Endothelial Cells: The cells lining blood vessels. Ferroptosis here disrupts the blood-air barrier and hampers regeneration.
From Mechanism to Therapy
The review emphasizes that because ferroptosis is a central driver of the disease, blocking it offers a viable treatment path. The authors summarize preclinical evidence showing that ferroptosis inhibitors—such as Ferrostatin-1 and the flavonoid Dihydroquercetin (DHQ)—can significantly alleviate lung inflammation and fibrosis in animal models.
"A comprehensive and in-depth understanding of the role of ferroptosis in pneumoconiosis is critical to enable the successful clinical translation of ferroptosis-targeted therapies," the authors state.
The study provides a conceptual framework for future research, suggesting that combining ferroptosis inhibitors with existing therapies could improve patient outcomes. It also calls for further investigation into how different lung cells communicate during this process to refine precision medicine approaches for occupational lung diseases.