Silencing Map3k7 attenuates BPD in premature infants by inhibiting caspase-1 mediated pyroptosis
Background: Bronchopulmonary dysplasia (BPD) is one of the most serious complications of premature infants. Pyroptosis is a substantial natural immune response, functioning in antagonizing infection. This study aims to explore the mechanism of Mitogen-activated protein 3 kinase 7 (Map3k7) affecting BPD by regulating caspase-1 mediated pyroptosis.Methods: The lung tissue and serum of pups were obtained by constructing BPD model rats. The morphology of lung tissue in the control group and the model group was observed by hematoxylin-eosin staining. RNA-seq and protein-protein interaction network (PPI) were performed to find the key genes. The regulation mechanism of key gene on pyroptosis was explored by cell experiments and gene silencing technology. The expressions of classical pyroptosis pathway related factors were detected by qRT-PCR and western blot.Results: Intraamniotic injection of lipopolysaccharide (LPS) simulating BPD can disrupt alveolar development in neonatal rats. Through RNA-seq and PPI analysis, it was determined that Map3k7, Prtn3, Itgax and Cd163 were related to pyroptosis, and Map3k7 was selected as the crucial gene. In this study, compared with LPS group, silencing Map3k7 promoted the proliferation of AEC-II, and reduced the expression level of inflammatory factors induced by LPS and inhibited oxidative stress, as well as pyroptosis related-protein expression.Conclusions: Silencing Map3k7 attenuates BPD by inhibiting pyroptosis, providing a direction for the treatment of BPD in premature infants.