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Departments of 1 Anatomy and Cell Biology and 2 Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7400
Neuropilin-1, a
neuronal cell surface semaphorin III receptor protein important for
axonal guidance in developing peripheral nervous system efferents, has
also been identified as a vascular endothelial growth factor (VEGF)
receptor on endothelial cells. To evaluate its expression in kidney, we
carried out RT-PCR on newborn and adult total renal RNAs. A 403-bp
product, which was predicted to be that from neuropilin-1 mRNA, was
found in both samples. Nucleotide sequencing confirmed that these
products encoded neuropilin-1. Northern analysis of newborn and adult
kidney RNA showed specific hybridization to appropriately sized bands
of ~6 kb. In situ hybridization with a mouse-specific antisense
neuropilin-1 35S-cRNA probe showed distinct glomerular
localization on sections from both newborns and adults. Similar
patterns of hybridization were seen in sections treated with antisense
cRNA probes against another VEGF receptor, Flk1, and with VEGF probes.
However, the VEGF hybridization signal was markedly less in adult
glomeruli than those for neuropilin-1 and Flk1. Because neuropilin-1
specifically binds VEGF165 in humans, we carried out RT-PCR
on mouse kidney RNA with primers that amplified the three alternatively
spliced isoforms of VEGF mRNA. Our analysis showed that for both
newborn and adult kidneys, the relative abundance of VEGF mRNA was
VEGF164
VEGF120 > VEGF188. We conclude that the expression of neuropilin-1, in conjunction with Flk1 and VEGF164, jointly contributes
to the development and maintenance of glomerular capillaries.
kidney glomerular development; endothelium; angiogenesis
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