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 [
Go to this article.]
Figure 4VEGF-A decreased CNV through VEGFR-1–induced negative transduction of VEGFR-2 via SHP-1. (
A) Representative figure shows VEGFR-1 phosphorylation levels in RPE/choroid of eyes before injury (control) and 30 minutes after intravitreous injection of PBS or VEGF-A, 1 day after injury.
n = 5. WB, Western blot. (
B) Representative figure shows that VEGF-A, injected 1 day after laser injury, increased interaction of SHP-1 with VEGFR-2 and reduced VEGFR-2 phosphorylation at 30 minutes after injection, 1 day after injury, and before injury (control), without affecting VEGFR-2 expression. Densitometric ratios of SHP-1 to total VEGFR-2 and of phosphorylated (P) to total (T) VEGFR-1 or VEGFR-2 are shown before (control) and after injury. Ratios were normalized to control values.
n = 5. (
C) VEGF-A–induced CNV suppression was abrogated by BMOV (0.16 μmol) and sodium stibogluconate (SSG) (0.56 nmol) in wild-type mice.
n = 12 per data point. (
D) VEGF-A did not significantly suppress CNV in
Shp1–/– mice (
n = 12 per data point;
P = 0.44). *
P < 0.05 compared with PBS. VEGF-A, 0.1 pmol.
