Human OPN-derived peptide SV prevents BPD model through interacting with KIF5B to repair mitochondrial damage and inhibit apoptosis.

Bioactive components in breast milk offer a new therapeutic strategy for bronchopulmonary dysplasia (BPD). While osteopontin (OPN) is supplemented in formula to promote neonatal growth, the therapeutic role of its derived peptide, SVVYGLR (SV), in BPD remains unexplored. This study aimed to elucidate SV's therapeutic mechanisms in BPD. The results revealed that SV significantly enhances cell viability, inhibits hyperoxia/LPS-induced apoptosis, and repairs alveolar epithelial injury. Molecularly, SV restores mitochondrial integrity, upregulates the anti-apoptotic protein BCL-2, and downregulates the pro-apoptotic protein Bax. In vivo experiments showed SV reduced hyperoxia/LPS-triggered BPD-like injury, evidenced by neonatal mice gaining weight, improved lung histology, and increased alveolar counts and septal thickness. Preliminary mechanistic studies revealed that SV interacts with KIF5B and enhances its binding to mitochondria. In conclusion, SV improves BPD by repairing mitochondrial damage and inhibiting apoptosis via KIF5B interaction. This study identified new potential targets and therapeutic strategies for BPD management.