INT240113

Context Info Confidence 0.30 First Reported 2008 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 11 Total Number 16 Disease Relevance 10.88 Pain Relevance 2.24

cell differentiation (Nrp1) cytosol (Nrp1) cell adhesion (Nrp1) plasma membrane (Nrp1)

Anatomy Link Frequency sensory neurons 3 F11 2 spinal nerve 1 macrophages 1 neuronal 1 Nrp1 (Mus musculus)

Pain Link Frequency Relevance Heat Nerve growth factor 294 99.48 rheumatoid arthritis 114 99.20 Inflammation 132 99.04 c fibre 18 88.08 Spinal cord 42 87.08 Antihistamine 12 79.60 substance P 48 57.96 Antinociceptive 6 56.64 antagonist 16 51.40 Arthritis 16 50.00

Disease Link Frequency Relevance Heat Targeted Disruption 46 99.88 Eczema 648 99.22 Rheumatoid Arthritis 116 99.20 INFLAMMATION 127 99.04 Injury 21 98.80 Acanthosis 12 97.88 Shock 6 96.88 Neuroblastoma 7 96.68 Disease 44 94.48 Pruritus 144 92.80

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Event

Anatomy

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However, the combination therapy of Sema3A with anti-NGF antibody may not be justified for AD, because NGF is known to increase the expression levels of NRP-157 and to augment the effect of Sema3A to induce axon repulsion (or growth cone collapse) of dorsal root ganglia neurons.58 Further studies should be required to elucidate the mechanism of action of Sema3A on AD.

Gene_expression (expression) of NRP-157 in growth cone associated with nerve growth factor, shock and eczema

1) Confidence 0.30 Published 2010 Journal Allergy, Asthma & Immunology Research Section Body Doc Link PMC2946701 Disease Relevance 0.92 Pain Relevance 0.22

Semaphorin 3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons by exerting the plexin-A1-4 and neuropilin-1 (NRP-1) of its receptors.32,33 Fig. 10 shows semaphorin family and its receptors.

Gene_expression (shows) of NRP-1 in sensory neurons

2) Confidence 0.30 Published 2010 Journal Allergy, Asthma & Immunology Research Section Body Doc Link PMC2946701 Disease Relevance 1.84 Pain Relevance 0.40

Semaphorin 3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons by exerting the plexin-A1-4 and neuropilin-1 (NRP-1) of its receptors.32,33 Fig. 10 shows semaphorin family and its receptors.

Gene_expression (exerting) of NRP-1 in sensory neurons

3) Confidence 0.30 Published 2010 Journal Allergy, Asthma & Immunology Research Section Body Doc Link PMC2946701 Disease Relevance 1.84 Pain Relevance 0.43

Semaphorin 3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons by exerting the plexin-A1-4 and neuropilin-1 (NRP-1) of its receptors.32,33 Fig. 10 shows semaphorin family and its receptors.

Gene_expression (exerting) of neuropilin-1 in sensory neurons

4) Confidence 0.30 Published 2010 Journal Allergy, Asthma & Immunology Research Section Body Doc Link PMC2946701 Disease Relevance 1.83 Pain Relevance 0.43

In addition, Sema3A and NRP-1 of its receptors expressed in human keratinocytes52 may be relevant to the above-mentioned suppressive effect of Sema3A on acanthosis observed in our present experiment.

Gene_expression (expressed) of NRP-1 associated with acanthosis

5) Confidence 0.27 Published 2010 Journal Allergy, Asthma & Immunology Research Section Body Doc Link PMC2946701 Disease Relevance 0.49 Pain Relevance 0.06

Also Sema3A and NRP-1 of its receptors expressed in dendritic cells and T cells53,54 may be relevant to the immunological effect of Sema3A such as suppression of CD4+ T cells infiltration and IL-4 production observed in the AD-like lesions in NC/Nga mice treated with Sema3A, as above-mentioned.

Gene_expression (expressed) of NRP-1 in T cells associated with eczema

6) Confidence 0.27 Published 2010 Journal Allergy, Asthma & Immunology Research Section Body Doc Link PMC2946701 Disease Relevance 0.40 Pain Relevance 0.07

NP-1 was found to be highly expressed in the lining layer, and on infiltrating leukocytes and endothelial cells of the rheumatoid synovium.

Gene_expression (expressed) of NP-1 in endothelial cells

7) Confidence 0.23 Published 2008 Journal Mediators of Inflammation Section Body Doc Link PMC2638142 Disease Relevance 0.61 Pain Relevance 0.22

Npn-1 and Npn-2 expression levels were determined by quantitative PCR on an Applied Biosystems 7300 real-time PCR system using SYBR green master mix (Applied Biosystems) and 0.3 mM oligonucleotide (Eurogentec) (table 2).

Gene_expression (expression) of Npn-1

8) Confidence 0.13 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2841193 Disease Relevance 0.34 Pain Relevance 0

Rubrospinal neurons express Npn-2 but not Npn-1.

Neg (not) Gene_expression (express) of Npn-1 in neurons

9) Confidence 0.13 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2841193 Disease Relevance 0.25 Pain Relevance 0.08

We initially developed two shRNAs for Npn-1 and seven for Npn-2 and evaluated their capacity to silence Npn-1 or Npn-2 expression in F11 cells.

Gene_expression (expression) of Npn-1 in F11

10) Confidence 0.13 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2841193 Disease Relevance 0.05 Pain Relevance 0

As a primary screening method to assess knockdown efficiency of endogenous Npn-1 and Npn-2 expression levels, F11 cells, a fusion cell line derived from of rat embryonal DRG and mouse neuroblastoma cells [25], were transduced with lentiviral vectors encoding green fluorescent protein (GFP) and an shRNAs directed against Npn-1 or Npn-2 (Figure 1a).

Gene_expression (expression) of Npn-1 in F11 associated with neuroblastoma

11) Confidence 0.10 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2841193 Disease Relevance 0.10 Pain Relevance 0

Our data shows that we were able to generate shRNA sequences that efficiently knock down Npn-1 and Npn-2 expression in a neuronal cell line using a lentiviral vector delivery system.

Gene_expression (expression) of Npn-1 in neuronal associated with targeted disruption

12) Confidence 0.10 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2841193 Disease Relevance 0.47 Pain Relevance 0

The aim of the present study was to develop an RNAi based strategy to knock down the expression of the class-3 Semaphorin receptors Npn-1 and Npn-2 in neurons of spinal nerve tracts and to employ this methodology to investigate the proposed involvement of these receptors in the failure of CNS-axons to regenerate.

Gene_expression (expression) of Npn-1 in spinal nerve associated with targeted disruption

13) Confidence 0.10 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2841193 Disease Relevance 0.27 Pain Relevance 0

QPCR analysis revealed that Npn-1 expression after transduction with two shRNA sequences was significantly reduced to 31.4 ± 1.8% and 17.5 ± 3.4% respectively (Figure 2a).

Gene_expression (expression) of Npn-1

14) Confidence 0.10 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2841193 Disease Relevance 0.09 Pain Relevance 0

NP-1 was found to be highly expressed in the lining layer, and on infiltrating leukocytes and endothelial cells of the rheumatoid synovium.

Gene_expression (expressed) of NP-1 in leukocytes

15) Confidence 0.08 Published 2008 Journal Mediators of Inflammation Section Body Doc Link PMC2638142 Disease Relevance 0.61 Pain Relevance 0.22

PUMA-g is a G-protein-coupled transmembrane receptor that was initially identified in a microarray screen of macrophages activated with TNF-?

Gene_expression (coupled) of transmembrane receptor in macrophages

16) Confidence 0.05 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2483455 Disease Relevance 0.76 Pain Relevance 0.13

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