Bleomycin-induced lung fibrosis and dysfunction is exacerbated by G6PD deficiency
- Darren Lobo
- Apr 23
- 1 min read
Authors: Christina Signoretti, Samuel Fatehi, Rhonda Drewes, Francesca Cendali, Monika Dzieciatkowska, Angelo D'Alessandro, Yongho Bae, Sachin A Gupte
Summary: Pulmonary fibrosis is driven in part by oxidative stress and altered metabolism, yet the role of glucose metabolism in extracellular matrix (ECM) synthesis remains unclear. Using a bleomycin-induced rat model, we found that a loss-of-function G6PD variant (G6PDS188F) markedly exacerbates lung fibrosis compared with wild-type controls, evidenced by increased lung volume, collagen deposition, and profibrotic protein expression. Mechanistically, this effect is associated with heightened oxidative stress, NRF2 pathway disruption, and downregulation of the polyamine metabolite spermidine, suggesting that impaired antioxidant and polyamine pathways promote excessive ECM synthesis in pulmonary fibrosis.
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