Silencing Map3k7 suppresses pyroptosis to alleviate bronchopulmonary dysplasia through inhibiting the TGF-β1/Smad3 pathway.

Bronchopulmonary dysplasia (BPD) is a serious complication in premature infants. This study aimed to investigate the mechanism of mitogen-activated protein 3 kinase 7 (Map3k7) affecting BPD by regulating caspase-1 mediated pyroptosis. The morphology of the lung tissue was observed using hematoxylin-eosin staining. TUNEL staining was performed to detect tissue apoptosis. RNA-seq and protein-protein interaction (PPI) network were performed to identify hub genes. Cell viability and apoptosis was analyzed using the CCK-8 assay and flow cytometry, respectively. Pyroptosis-related factors, inflammatory factors, oxidative stress indicators, and pathway-related proteins were detected using ELISA, qRT-PCR, and Western blotting. Hyperoxia-induced neonatal rats showed alveolar simplification with increased alveolar lumen, and decreased density of secondary alveolar cristae, demonstrating the successful BPD model. Map3k7 was identified as the crucial gene that was upregulated in BPD. Silencing Map3k7 promoted cell proliferation and suppressed apoptosis, inflammation, oxidative stress, and pyroptosis in hyperoxia-induced AEC-II, and alleviated BPD progression in hyperoxia-induced rats. Furthermore, silencing Map3k7 inhibited the TGF-β1/Smad3 pathway, and SRI-011381, the TGF-β pathway activator, weakened the inhibitory effects of silencing Map3k7 on hyperoxia-induced AEC-II. Silencing Map3k7 suppressed pyroptosis to alleviate BPD through inhibiting the TGF-β1/Smad3 pathway, providing a direction for the treatment of BPD in premature infants.