Pirfenidone Attenuates Hyperoxia-induced Lung Injury and Pulmonary Hypertension in a Mouse Model of Bronchopulmonary Dysplasia in Newborn Mice

Bronchopulmonary dysplasia (BPD) is a major complication of prematurity frequently accompanied by life-threatening pulmonary hypertension (PH). Pirfenidone (PFD), an anti-fibrotic drug approved for adults, exhibits multimodal properties but its therapeutic efficacy and underlying mechanisms in neonatal BPD-associated PH(BPD-PH) remain to be elucidated. This study aimed to evaluate the therapeutic potential of PFD and its underlying mechanisms in a hyperoxia-induced mouse model of BPD. We found that PFD treatment enhanced alveolarization, reduced pulmonary fibrosis, attenuated pulmonary vascular remodeling and right ventricular hypertrophy. These protective effects were accompanied by decreased expression of inflammatory cytokines, improved oxidative stress profiles, and concomitant suppression of Wnt5A signaling and TGF-β1/Smad pathway activation. Collectively, these findings identify PFD as a potential modulator of lung injury and vascular remodeling in experimental BPD. However, as these observations are derived from a preclinical model, further studies are required to define safety, dosing, and efficacy prior to clinical translation.