Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases
J. Clin. Invest. Vera Eremina, et al. 111:707 doi:10.1172/JCI17423 [
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Figure 6Mice that overexpress the 164 isoform of VEGF-A in their podocytes develop collapsing glomerulopathy. (
a and
b) Whole-mount images of VEGF-overexpressing kidneys at 5 days. The kidneys demonstrate many surface hemorrhages. (
c) A glomerulus stained with H&E from a wild-type littermate. (
d) A glomerulus from a transgenic VEGF-overexpressing mouse demonstrates global collapse of the capillary tuft toward the vascular pole of the glomerulus. A single patent capillary loop that appears dilated is identified (Cap). In addition, Bowman’s space (BS) is enlarged. (
e) A 5-day-old wild-type glomerulus is stained with silver methenamine that recognizes basement membranes (black). Note the intricate pattern of GBM that lines the capillary loops between endothelial cells and podocytes. (
f) In contrast, a transgenic glomerulus demonstrates complete collapse of the capillary network. (
g) A high-power view of the capillary loops (Cap) in a wild-type glomerulus. (
h) In contrast, the few patent capillary loops identified at 5 days of age in the transgenic mice demonstrate increased diameter and multiple endothelial cell nuclei (arrowheads). (
i) A wild-type capillary loop at 5 days of age. Note the fenestrated endothelium (arrow). Although a portion of an endothelial cell body is identified (arrowhead), glomerular endothelial cell nuclei are difficult to find on EM sections. (
j) In a transgenic patent capillary loop at 5 days of age, three endothelial cell nuclei are easily identified (arrowheads). Magnification in
a and
b: ×60; in
c–
f: ×225; in
g and
h: ×1,000. In
i, bar = 2,000 nm; in
j, bar = 5,000 nm.