Figure 5
From: GSDMD deficiency ameliorates hyperoxia-induced BPD and ROP in neonatal mice
GSDMD-KO reduces hyperoxia modulation of inflammatory, tissue remodeling, and developmental pathways in the neonatal lung. (A) Principal component analysis (PCA) plot showing separation of WT and GSDMD-KO mice by PC1 and RA and O2 animals by PC2. (B) Heatmap of differentially expressed genes in WT-O2 vs WT-RA and KO-O2 vs KO RA. (C) UpSet plot showing overlap of genes differentially regulated by hyperoxia in WT and GSDMD-KO lungs. Hyperoxia modulated the expression of 3926 genes in WT and 3567 genes in GSDMD-KO lungs. (D) Overrepresentation analysis using Toppcluster to identify similarities and dissimilarities of Gene Ontology terms and pathways modulated by hyperoxia in WT and GSDMD-KO lungs. Bars represent the log P-value, and the number of genes associated with each term is displayed at the end of the bar. In GSDMD-KO lungs, genes induced by hyperoxia were more strongly associated with TNF superfamily cytokine production, cellular extravasation, and cellular response to IFN-γ, while suppressed genes in GSDMD-KO were uniquely associated with lobar bronchus epithelium development and cell receptor signaling pathways. n = 3 animals/group. qRT-PCR validation of differentially expressed genes between hyperoxia-exposed WT and hyperoxia-exposed GSDMD-KO lungs included Alas2 (E), Scl4a1 (F), Edn1 (G), Mif (H), Pik3cg (I), and Trem 2 (J). n = 4/group. *P < 0.05, **P < 0.01, ***P < 0.001, WT-O2 vs WT-RA. #P < 0.05, ##P < 0.01, WT-O2 vs KO-O2.
