Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A
J. Clin. Invest. Miho Nozaki, et al. 116:422 doi:10.1172/JCI26316 [
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Figure 6SPARC regulated VEGF-A effects on CNV. (
A) Constitutive (control) RPE/choroid expression of SPARC was decreased 1 day after laser injury and recovered 2 days after injury. Figure is representative of 3 experiments. (
B and
C) Immunoprecipitation of 3 independent samples revealed that VEGF-A interacted with SPARC (
B) but not IGF binding protein-3 (IGFBP-3) (
C) in vivo. (
D) CNV inhibition by VEGF-A injected 1 day after injury was abolished by recombinant human SPARC (rhSPARC) and restored by neutralizing anti-SPARC Ab (80 pmol). *
P < 0.05 compared with PBS. Recombinant SPARC injection alone (white bar) did not change CNV compared with PBS. (
E) Neutralizing anti-SPARC Ab (26.7 pmol) but not control mouse IgG abrogated CNV increase induced by VEGF-A 1 day before injury. *
P < 0.05 compared with PBS. (
F) VEGF-A injected 1 day before laser injury increased CNV in
SPARC+/+ mice but not in
SPARC–/– mice. VEGF-A injected 1 day after laser injury decreased CNV in
SPARC+/+ and
SPARC–/– mice. *
P < 0.05 compared with PBS injection on the same day. VEGF-A, 0.1 pmol.
n = 10–14 per data point (
D–
F).