Fig 1.
A: Boxplot of sample normalization for the FGR dataset GSE147776; B: Volcano plot of differentially expressed genes for the FGR dataset GSE147776; C: Heatmap of differentially expressed gene clustering for the FGR dataset GSE147776; Da: GO enrichment bubble plot of DEGs; Db: GO enrichment bar plot of DEGs; Ea: KEGG enrichment bubble plot of DEGs; Eb: KEGG enrichment lollipop plot of DEGs; F: Scatter plot of BRD4 and KEAP1 correlation; G: Scatter plot of KEAP1 and Nrf2 correlation; H: Heatmap of molecular interactions among BRD4, NOX4, NOX2, Nrf2, SHP2, P53, VEGFR, PI3K, CREB, JNK, and P38; I: Lollipop plot of YAP and effector factor correlations (CREB, VEGF, VEGFR2, SOX9, OCT4, SOX2, Ki-67, Nrf2).
Fig 2.
SHP2 regulates the ROS/BRD4 and PI3K/YAP/PIGF pathways.
A: Western blot analysis of NOX4, nuclear BRD4, p-SHP2, p-PI3K, nuclear YAP, Nrf2, and PIGF protein expressions in EPCs in the following six groups: NC group, Model group, Model + JQ-1 group, Model + JQ-1 + PHPS1 group, Model + JQ-1 + PHPS1 + 740Y-P group, and Model + JQ-1 + PHPS1 + 740Y-P + Verteporfin group, GAPDH as the control protein; B: Statistical analysis of relative protein expression levels. N = 3; Data are expressed as mean ± standard deviation; Different lowercase letters on the same column indicate significant differences between groups at P < 0.05, while different uppercase letters indicate significant differences at P < 0.01.
Fig 3.
Effect of SHP2 on endothelial progenitor cell angiogenic capacity.
A: Western blot analysis of VEGF and HIF1α protein expressions in EPCs in the following six groups: NC group, Model group, Model + JQ-1 group, Model + JQ-1 + PHPS1 group, Model + JQ-1 + PHPS1 + 740Y-P group, and Model + JQ-1 + PHPS1 + 740Y-P + Verteporfin group, along with statistical analysis of relative protein expression levels. GAPDH as the control protein; B: Tube formation assay measuring vascular intersections, total vessel length, and vessel branch length, along with statistical analysis of number of neovessels visual field. N = 3; Data are expressed as mean ± standard deviation; Different lowercase letters on the same column indicate significant differences between groups at P < 0.05, while different uppercase letters indicate significant differences at P < 0.01.
Fig 4.
SHP2 induces endothelial progenitor cell activation to improve late-onset fetal growth restriction.
A: Western blot analysis of OCT4, SOX2, and C-Myc protein expressions in EPCs in the following six groups: NC group, Model group, Model + JQ-1 group, Model + JQ-1 + PHPS1 group, Model + JQ-1 + PHPS1 + 740Y-P group, and Model + JQ-1 + PHPS1 + 740Y-P + Verteporfin group, along with statistical analysis of relative protein expression levels. GAPDH as the control protein; B: Colony formation assay observing EPCs proliferation, along with statistical analysis of number of cloned cells; C: Flow cytometry analysis of the cell cycle, along with statistical analysis of cell cycle distribution; D: Flow cytometry analysis of cell apoptosis, along with statistical analysis of apoptosis rate. N = 3; Data are expressed as mean ± standard deviation; Different lowercase letters on the same column indicate significant differences between groups at P < 0.05, while different uppercase letters indicate significant differences at P < 0.01.
Fig 5.
SHP2 induces endothelial progenitor cell activation by regulating ROS/BRD4 and PI3K/YAP/PIGF, improving late-onset fetal growth restriction.