The molecular mechanisms of gas signaling molecules in bronchopulmonary dysplasia related lung injury

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic respiratory disease in preterm infants. Its pathogenesis is linked to multiple factors including lung immaturity secondary to preterm birth, hyperoxia exposure, mechanical ventilation-induced injury, and inflammatory responses. Characterized by alveolar simplification and abnormal pulmonary vascular development as the core pathological features, BPD exerts a profound negative impact on the long-term prognosis of affected infants. As endogenous small-molecule substances, gas signaling molecules play a pivotal role in regulating BPD related lung injury by virtue of their extensive biological properties. Among these molecules, nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H 2 S) have been subjected to extensive and in-depth investigations. This narrative review summarizes the mechanisms through which the above-mentioned gas signaling molecules modulate BPD-related lung injury. More importantly, this review comprehensively discusses the influences of crosstalk among the three gas signaling molecules on BPD. It objectively elaborates the protective effects of gas signaling molecules in BPD-related lung injury as well as the limitations of their clinical application. The findings lay a theoretical foundation for developing refined and individualized clinical prevention and treatment regimens of BPD based on gas signaling molecules in future clinical practice.