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Updated: Jan 8, 2026
02:46
A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
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Bleomycin-induced lung fibrosis and dysfunction is exacerbated by G6PD deficiency
Christina Signoretti1, Samuel Fatehi1, Rhonda Drewes2
1Department of Pharmacology, New York Medical College, Valhalla, New York, United States.
American Journal of Physiology. Lung Cellular and Molecular Physiology
|December 16, 2025
Summary
A genetic variant in glucose-6-phosphate dehydrogenase (G6PD) exacerbated pulmonary fibrosis in rats, increasing collagen and oxidative stress. This highlights metabolic pathway dysregulation in fibrosis development.
Area of Science:
- Pulmonary Medicine
- Metabolic Research
- Genetics
Background:
- Pulmonary fibrosis (PF) is a debilitating lung disease with high mortality.
- Oxidative stress and metabolic alterations are implicated in PF, but glucose metabolism's role in extracellular matrix (ECM) synthesis is unclear.
- Understanding these pathways is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate altered metabolic pathways contributing to bleomycin sulfate (BLM)-induced pulmonary fibrosis.
- To determine the effect of a glucose-6-phosphate dehydrogenase (G6PD) variant (S188F) on BLM-induced PF in rats.
Main Methods:
- Induction of pulmonary fibrosis using nebulized bleomycin sulfate (BLM) in G6PD variant (G6PDS188F) and wild-type (WT) rats.
- Histological analysis (Masson's Trichrome, Ashcroft scoring) and hydroxyproline quantification for collagen deposition.
- Mass-spectrometry-based proteomics, spatial proteomics, and metabolomics to identify protein and metabolite changes.
Main Results:
- BLM induced greater lung tissue volume and collagen deposition in G6PDS188F rats compared to WT rats.
- Proteomics confirmed increased expression of pro-fibrotic proteins (e.g., collagen1a1) in G6PDS188F + BLM lungs.
- BLM increased KEAP1, decreased NRF2 activity, raised oxidized glutathione, and down-regulated spermidine in G6PDS188F rats.
Conclusions:
- The G6PDS188F variant exacerbates BLM-induced pulmonary fibrosis in rats.
- Dysregulated polyamine metabolism and antioxidant state (oxidative stress) contribute to increased ECM synthesis in this model.
- Findings suggest G6PD variants may influence PF susceptibility and progression.
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