Fig 1: Targeting BMP signaling suppresses onset of AD in mice. (A) Monocle analysis showing the ordering of FB2 in pseudotime. Each dot is a cell. Each color indicates a cell state. (B) Heatmap to display different blocks of top 1,000 differentially expressed genes (DEGs) along the pseudotime trajectory (A). (C) Schematic of in vivo intervention experiment showing the administration time point of inhibitors or activators of pathways selected in Figure S8. (D) Representative images showing the effects of different compounds on aortas in mouse AD model. (E) Maximal ascending aortic diameter in indicated groups. *p < 0.05 compared to Saline group (One-way ANOVA). (F) Systolic blood pressure at different time points following treatment. **p < 0.01, ***p < 0.001 compared to Saline group (One-way ANOVA). For D-F, saline, n = 9; PDTC, n = 9; LDN-193189, n = 9; GW7647, n = 9; Oroxin B, n = 9. (G) Incidence of aortic dissection following treatment. (H) Co-staining of dFB2 marker PDPN, dFB2-specific ligand ADAM12 and corresponding SMC receptor ITGB1in mice aorta sections. White arrows indicate PDPNhigh cells, red arrows indicate interaction between ADAM12 and ITGB1. Scale bars, 50 µm (left image); 25 µm (magnification). FL, false lumen. Images are representative of 3 independent experiments (3 samples each time point).
Fig 2: FB2 affects SMC behaviors via ligand-receptor interaction. (A) Bubble chart to show putative ligand-receptor pairs between differentially expressed ligands in Non-AD state (n-) or AD state (d-) of each cell cluster and corresponding receptors expressed in SMCs. (B) Quantification of ligand-receptor pairs (A) in each cell type. (C) Co-staining of dFB2-specific marker PDPN, dFB2-specific ligand ADAM12 and corresponding SMC receptor ITGB1 in human aorta sections. White arrows indicate interaction between ligand and receptor. Scale bars, 100 µm (leftmost column); 50 µm (magnifications). M, media; FL, false lumen; A, adventitia. Representative images are from 3 independent experiments (3 samples each time point). (D, E) Quantification of ADAM12 (D) and ITGB1 (E) in (C). n = 3. ***p < 0.001 (Wilcoxon rank-sum test). (F) Schematic to show culture of human aortic SMCs (HAVSMCs) with conditioned medium from dFB2. (G) Volcano plot to show DEGs in HAVSMCs cultured with conditioned medium. Red and blue colors respectively represent up- and down-regulated genes in treated HAVSMCs cultured in dFB2-conditioned medium. (H) Gene Set Enrichment Analysis (GSEA) showing that genes up-regulated in HAVSMCs cultured in conditioned medium were enriched for genes that were highly expressed in AD state.
Supplier Page from Proteintech Group Inc for Human ADAM12 ELISA Kit