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. 2023 Jan 12;120(3):e2213317120. doi: 10.1073/pnas.2213317120

Fig. 3.

Fig. 3.

Competitive SMAD signaling pathways regulate Robo4 expression both positively and negatively. (A) Robo4 expression levels in HUVECs treated with siRNA for SMAD2 and SMAD3 (n = 4, **P < 0.01 by the unpaired t test). (B) Robo4 expression level in TGF-β1/2-treated HUVECs under normal (n = 4) or Matrigel conditions (n = 5, *P < 0.05, **P < 0.01 by Dunnett’s test). (C) Robo4 expression levels in HUVECs treated with BMP9 (n = 4, **P < 0.01 by the unpaired t test). (D) Robo4 expression levels in HUVECs treated with BMP9 and siRNA for SMAD1 and SMAD5 (n = 4, **P < 0.01; N.S., not significant by Tukey’s test). (E) Robo4 expression levels in HUVECs treated with K02288 and BMP9 (n = 4, **P < 0.01 by Tukey’s test). (F) Robo4 expression levels in HUVECs cultured in Matrigel containing K02288 (n = 4, **P < 0.01; N.S., not significant by the unpaired t test). (G) Schematic illustration of positive and negative Robo4 regulation by TGF-β-ALK5-SMAD2/3 and BMP9-ALK1-SMAD1/5 signaling pathways. Data are expressed as the mean ± SEM.