Ephx2 Deficiency Reduces COPD by Blocking Ferroptosis in Mice

Chronic Obstructive Pulmonary Disease (COPD) presents a significant global health burden, contributing to over 3 million deaths annually. Current therapeutic approaches have limited effectiveness, highlighting an urgent need for innovative treatment strategies that address underlying pathophysiological mechanisms, such as ferroptosis.

In this preclinical study, we employed a mouse model to investigate the role of Ephx2 deficiency in the modulation of COPD induced by chronic exposure to cigarette smoke. Mice lacking the Ephx2 gene were exposed to smoke for 12 weeks. The primary endpoint was the assessment of lung function through measuring forced expiratory volume (FEV1) and histological evaluation of lung tissue.

Ephx2-deficient mice demonstrated a 40% reduction in lung inflammation (measured by neutrophil count), and a 30% improvement in FEV1 compared to control mice. Ferroptosis markers, including lipid peroxidation levels, were 50% lower in Ephx2-deficient mice, indicating a significant protective effect against oxidative stress-induced cell death.

These findings support the potential of Ephx2 as a novel therapeutic target for COPD by preventing ferroptosis, suggesting implications for therapeutic development. However, the study is limited to an animal model, and further validation in human cohorts is necessary before clinical application.

Original citation address: https://www.besjournal.com/en/article/doi/10.3967/bes2026.012