Phosphocreatine mitigates pulmonary fibrosis in STZ-induced diabetic rats with bleomycin injury through TGF-β/Smad and Wnt/β-catenin pathways.

Diabetes accelerates pulmonary fibrosis through chronic inflammation, oxidative stress, and fibroblast activation. Key signaling pathways, including TGF-β/Smad and Wnt/β-catenin, drive fibroblast activation and epithelial-mesenchymal transition (EMT), contributing to lung fibrotic remodeling. This study investigated the therapeutic potential of phosphocreatine (PCr) in a combined model of STZ-induced diabetes and bleomycin-induced lung fibrosis. Histopathological changes were assessed using H&E, Masson's Trichrome, and Sirius Red staining, revealing alveolar injury, inflammatory infiltration, and collagen deposition. Mitochondrial function was evaluated by measuring ATP production and citrate synthase activity. PCr treatment markedly mitigated lung fibrosis, preserved alveolar structure, restored mitochondrial bioenergetics, and reduced inflammation and oxidative stress, likely via modulation of TGF-β/Smad and Wnt/β-catenin signaling. These findings suggest that PCr may serve as a promising multi-targeted therapeutic strategy for diabetes-associated pulmonary fibrosis.