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

Area of Science:

• Neonatal Medicine
• Molecular Biology
• Pathology

Background:

• Bronchopulmonary dysplasia (BPD) is a significant respiratory complication in premature infants.
• The underlying molecular mechanisms of BPD pathogenesis require further elucidation.
• Mitogen-activated protein 3 kinase 7 (Map3k7) has emerged as a potential regulator in inflammatory lung diseases.

Purpose of the Study:

• To investigate the role of Map3k7 in BPD development.
• To explore the mechanism by which Map3k7 regulates caspase-1 mediated pyroptosis in BPD.
• To identify Map3k7 as a potential therapeutic target for BPD.

Main Methods:

• Establishment of a hyperoxia-induced neonatal rat model of BPD.
• Hematoxylin-eosin and TUNEL staining for lung tissue morphology and apoptosis.
• RNA-sequencing and protein-protein interaction network analysis to identify key genes.
• Cell viability, apoptosis, pyroptosis, inflammation, oxidative stress, and pathway-related protein analysis using CCK-8, flow cytometry, ELISA, qRT-PCR, and Western blotting.

Main Results:

• Hyperoxia exposure successfully induced BPD in rats, characterized by alveolar simplification.
• Map3k7 was significantly upregulated in BPD models and identified as a crucial gene.
• Silencing Map3k7 suppressed apoptosis, inflammation, oxidative stress, and pyroptosis in hyperoxia-induced alveolar epithelial cells type II (AEC-II) and alleviated BPD.
• Map3k7 inhibition suppressed the TGF-β1/Smad3 pathway, and TGF-β pathway activation reversed the protective effects of Map3k7 silencing.

Conclusions:

• Map3k7 plays a critical role in the pathogenesis of BPD by promoting pyroptosis via the TGF-β1/Smad3 pathway.
• Inhibition of Map3k7 demonstrates therapeutic potential for alleviating BPD in premature infants.
• Targeting Map3k7 offers a promising new direction for BPD treatment strategies.