Work

Attenuation of Experimental Bronchopulmonary Dysplasia by Dimethyl Fumarate

Year: 2026

Type: article

Abstract: BACKGROUND: Innovative therapies for bronchopulmonary dysplasia (BPD) in neonates are needed. Dimethyl fumarate (DMF) is a methyl ester of fumaric acid that is an approved drug. The goal was to explore the role of DMF in BPD utilizing a hyperoxia-induced murine model of experimental BPD. METHODS: In our mouse model of experimental moderate-BPD, DMF was administered on postnatal (PN) days 2 and 4. On PN14, we evaluated lung histology, lung morphometry, and used Western blotting. RESULTS: DMF improved lung histology in male and female mice, with recovery of chord length, septal thickness, and radial alveolar counts. There was a significant reduction in cell death, increase in cell proliferation, and lung vascularization after DMF treatment. Nuclear factor erythroid -2-related factor (Nrf-2) expression decreased, while nuclear factor-kappa-light-chain enhancer of activated B cells (NF-κB) expression levels increased in the BPD lungs. These effects were reversed after treatment with DMF. We found a decrease in heme oxygenase (HO)-1 expression after DMF treatment, with no change in selective mitochondrial markers of oxidative stress. CONCLUSION: This is the first study to demonstrate the efficacy of systemically administered DMF to promote the resolution of experimental moderate-BPD. DMF putatively acted via Nrf-2 -dependent and -independent cell signaling pathways. IMPACT: 1. Dimethyl fumarate (DMF) is an approved drug for lung fibrosis treatment. 2. We used our experimental moderate-BPD mouse model to evaluate the impact of DMF treatment. 3. DMF improved lung histology and morphometry, with a significant reduction in cell death, and an increase in cell proliferation and lung vascularization after DMF treatment. 4. Nrf-2 expression decreased in response to hyperoxia in male and female lungs, while NF-κB expression levels increased. These were reversed with DMF treatment. 5. This is the first study to demonstrate the efficacy of DMF to promote the resolution of experimental moderate-BPD in the mouse model.

Source: Pediatric Research

DOI: 10.1038/s41390-026-05039-8