Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis
J. Clin. Invest. Kazuhide Watanabe, et al. 114:898 doi:10.1172/JCI21152 [
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Figure 3KIAA1036 may act as a negative feedback regulator. (
A) Effect of KIAA1036 on the migration of HUVECs. Migration of HUVECs was analyzed as described in Methods. The indicated concentrations of growth factors and/or KIAA1036 protein were placed in the lower chamber of the Transwell insert. Values are expressed as mean ± SD of 4 samples. (
B) Effect of KIAA1036 on the migration of HASMCs or fibroblasts. Migration of HASMCs or fibroblasts was analyzed as described in Methods. The indicated combinations of PDGF, FGF-2, and KIAA1036 protein were placed in the lower chamber. Values are expressed as mean ± SD of 4 samples. (
C) Bell-shaped pattern of the VEGF-stimulated migration of HUVECs. The indicated concentrations of VEGF were placed in the lower chamber and HUVECs were plated in the upper chamber. Values are expressed as mean ± SD of 4 samples. (
D) Selective downregulation of KIAA1036 synthesis. HUVECs were incubated for 4 hours with 500 nM synthetic phosphorothioate ODNs or vehicle alone. Thereafter, HUVECs were stimulated with VEGF (1 nM) for 24 hours, and Western blotting for KIAA1036 was performed. AS, AS-ODN; S, S-ODN; Scr, Scr-ODN; v, vehicle. (
E) Modulation of the bell-shaped pattern of the VEGF effect by KIAA1036 AS-ODNs. HUVECs were incubated for 4 hours with 500 nM phosphorothioate ODNs. Thereafter, HUVECs were subjected to the migration assay described above. Values are expressed as mean ± SD of 4 samples. *
P < 0.05, **
P < 0.01.