Disease relevance of Nrp1

• In this study we investigated the expression of NP-1 mRNA in adult dorsal root ganglion (DRG) neurons in intact and lesioned animals [1].
• Neuropilin-1 mRNA was significantly up-regulated as early as 2 hours and persisted at least 28 days after focal cerebral ischemia [2].
• Activated astrocytes also exhibited neuropilin-1 immunoreactivity during 7 to 28 days of ischemia [2].

High impact information on Nrp1

• Neuropilin is a semaphorin III receptor [3].
• Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165 [4].
• Collapsin-1 rapidly disrupted the formation of lamellipodia and induced depolymerization of F-actin in an NRP1-dependent manner [4].
• The larger tumors with induced NRP1 expression were characterized by markedly increased microvessel density, increased proliferating EC, dilated blood vessels, and notably less tumor cell apoptosis compared to noninduced controls [5].
• When rats injected with AT2.1/NRP1 tumor cells were fed Dox, NRP1 synthesis was induced in vivo and AT2.1 cell tumor size was increased 2.5- to 7-fold in a 3-4 wk period compared to controls [5].

Biological context of Nrp1

• The presence of sema III in scar tissue and the concomitant expression of its receptor neuropilin-1 on regenerating olfactory axons suggests that semaphorin-mediated chemorepulsive signal transduction may contribute to the regenerative failure of these axons after bulbectomy [6].
• We investigated the molecular guidance mechanisms of GE cell migration in the neocortex and found neuropilin-1 (Npn-1) or neuropilin-2 (Npn-2) on the GE cells [7].
• However, induction of NRP1 did not affect tumor cell proliferation [5].
• Glomerular upregulation of the VEGF(164) co-receptor neuropilin-1 mRNA in nephritic rats was reduced by L-NIL treatment only on day 7 [8].
• Here we show that most adult rat DRG neurons, regardless of cell diameter/afferent phenotype, express neuropilin-1 protein in vitro [9].

Anatomical context of Nrp1

• Neuropilin-1, a sema III receptor, was expressed in injured neurons with projections to the lesion site, in a subpopulation of scar-associated cells and in blood vessels around the scar [10].
• We have examined mRNA and protein distribution for the axon guidance molecules semaphorin3A, 3F, 4F and semaphorin receptors neuropilin-1 and 2, 1-21 days after intramedullary axotomy of rat lumbar spinal cord motoneurons [11].
• Our results show that Np1 RNA and protein are up-regulated in the spinal cord after all these lesions but remain unaltered in the adjacent dorsal root ganglia [12].
• Blockade of NG2 with antibody and blockade of neuropilin 2 but not neuropilin 1 both promoted axon growth from astrocytes to meningeal cells [13].
• The current studies examined rat uterus neuropilin expression and regulation [14].

Associations of Nrp1 with chemical compounds

• Concomitant with increased NRP1 expression in response to a tetracycline homologue, doxycycline (Dox), basal cell motility, and VEGF(165) binding were increased three- to fourfold in vitro [5].
• Heparin enhanced Sema3A's binding to neuropilin-1-expressing cells and potentiated its growth cone collapsing activity [15].
• Sequencing and database searches identified three genes, thrombospondin-1, heparin sulfate 6-sulfotransferase, and neuropilin-1, which play important roles in angiogenesis and axon growth during development [16].
• Among other genes found to be most changed in the hippocampus were protein kinase C beta I and II, protein tyrosine phosphatase 1beta, neuropilin I and II, adenosine receptor A1, and metabotropic glutamate receptor 2/3 [17].

Other interactions of Nrp1

• Microarray analysis detected maximal mRNA expression for a wide variety of angiogenic factors including angiopoietin 1 and 2, both Tie receptors, VEGF-A and -D, VEGFR2, and neuropilin 1 [18].
• Using immunohistochemical and in situ hybridization methods we have here demonstrated that VEGF and its receptors Flk-1, Flt-1 and Neuropilin-1 mRNAs and proteins are induced after incisions in the rat spinal cord [19].
• The semaphorin 3A, neuropilin-1, growth-associated protein and collapsin response mediator protein 1-5 genes were expressed significantly higher during the early development stages than in adulthood while the opposite is true for the olfactory marker protein [20].
• The level of neuropilin-1, an accessory receptor of VEGF to main receptor corresponds with that of VEGF and ang-1 [21].
• Using cell sorting, RT-PCR, in situ hybridization or immunocytochemistry, we have examined the segregation of expression to neuronal and glial progenitors, and identified several that appeared to be enriched in neuronal (e.g. CDK5, neuropilin, EphrinB2, FGF11) or glial (e.g. CXCR4, RhoC, CD44, tenascin C) precursors [22].

Analytical, diagnostic and therapeutic context of Nrp1

• Semaphorin and neuropilin expression in motoneurons after intraspinal motoneuron axotomy [11].
• After DCC and rhizotomy, Np1 is expressed de novo around the injury and in the deafferentated dorsal horn, respectively, mainly by OX42-positive microglial cells [12].
• Using RT-PCR, in situ hybridization, Western blotting, and immunofluorescence, we have analyzed the expression of neuropilin 1 (Np1) in two models of spinal cord injury (spinal cord hemisection and dorsal column crush) and following dorsal root rhizotomy in adult rats [12].
• The authors measured neuropilin-1 expression in the adult ischemic brain using Northern blot, in situ hybridization, and immunohistochemistry [2].
• Sema3A and neuropilin-1 were detected in these depots by Western blotting [23].

References