INT139205

From wiki-pain
Jump to: navigation, search
Context Info
Confidence 0.45
First Reported 2006
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 27
Total Number 30
Disease Relevance 4.34
Pain Relevance 0.71

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cell differentiation (NRP1) cytosol (NRP1) signal transduction (NRP1)
extracellular region (NRP1) cell adhesion (NRP1) plasma membrane (NRP1)
Anatomy Link Frequency
endothelial cell 2
extensor digitorum longus 2
blood 1
muscle tissues 1
NRP1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Inflammation 47 95.48 Very High Very High Very High
Inflammatory mediators 4 94.56 High High
interstitial cystitis 4 92.72 High High
cytokine 21 72.44 Quite High
addiction 51 43.88 Quite Low
antagonist 51 37.36 Quite Low
Bioavailability 4 25.88 Quite Low
ischemia 35 6.56 Low Low
metalloproteinase 51 5.00 Very Low Very Low Very Low
Pain 23 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Bladder Cancer 2 96.36 Very High Very High Very High
Gastrointestinal Stromal Tumor 31 96.00 Very High Very High Very High
INFLAMMATION 52 95.48 Very High Very High Very High
Disease 164 94.00 High High
Cancer 168 93.96 High High
Interstitial Cystitis 4 92.72 High High
Adhesions 5 87.84 High High
Fracture Healing 32 87.64 High High
Adult Respiratory Distress Syndrome 112 87.56 High High
Familial Adenomatous Polyposis 48 85.72 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
VEGF165 is well recognized as an endothelial cell mitogen.
VEGF165 Binding (recognized) of in endothelial cell
1) Confidence 0.45 Published 2010 Journal American Journal of Physiology - Lung Cellular and Molecular Physiology Section Body Doc Link PMC2886605 Disease Relevance 0.23 Pain Relevance 0
Our simulations also predicted inconsequential effects from incorporating the newly purported binding interaction between NRP1 and VEGF121.
NRP1 Binding (interaction) of
2) Confidence 0.40 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Furthermore, when keeping VEGF165-NRP1 affinity at control (320 pM) and introducing VEGF121-NRP1 binding at an affinity 1.83× higher than that (in accordance with the ratio reported by Pan et al.), all system distributions were almost identical to those at control – because even then, the steady-state population of VEGF121-NRP1 only represented an insignificant 0.7% of total VEGF121 in muscle tissues.
NRP1 Binding (binding) of in muscle tissues
3) Confidence 0.40 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
We have previously developed several computational models of the in vivo biochemical interactions between VEGF121, VEGF165, VEGFR1, VEGFR2, NRP1, and the interstitial matrix in skeletal muscle, including: a spatially-averaged single-tissue model of the human vastus lateralis muscle at rest [54]; and several 3D models for predicting spatial molecular gradients and intra-muscular pro-angiogenic treatment outcomes in resting and exercising rat extensor digitorum longus muscle [55]–[58].
NRP1 Binding (interactions) of in extensor digitorum longus
4) Confidence 0.40 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0.31 Pain Relevance 0
The VEGF165 cDNA was cut with EcoRI and XhoI (Promega) followed by ligation using the T4 DNA Ligase System (Promega) purified from agarose gel with MiniElute Gel Extraction Kit (Qiagen) and introduced into pCMV-Script liniarised vector using the T4 DNA Ligase System (Promega).
VEGF165 Binding (ligation) of
5) Confidence 0.36 Published 2007 Journal Genomic Med Section Body Doc Link PMC2276892 Disease Relevance 0 Pain Relevance 0
Interestingly, VEGF165b binds the generic VEGF receptors (VEGF-R1 and VEGF-R2) but not neuropilin-1 (NRP-1), the binding to which now appears to be exon 8a dependant (6).
neuropilin-1 Binding (binding) of
6) Confidence 0.35 Published 2010 Journal American Journal of Physiology - Lung Cellular and Molecular Physiology Section Body Doc Link PMC2886605 Disease Relevance 0.05 Pain Relevance 0
Interestingly, VEGF165b binds the generic VEGF receptors (VEGF-R1 and VEGF-R2) but not neuropilin-1 (NRP-1), the binding to which now appears to be exon 8a dependant (6).
NRP-1 Binding (binding) of
7) Confidence 0.35 Published 2010 Journal American Journal of Physiology - Lung Cellular and Molecular Physiology Section Body Doc Link PMC2886605 Disease Relevance 0.05 Pain Relevance 0
VEGF165b binds to VEGF-R2 with equal affinity to VEGF165, but it also phosphorylates VEGF-R2 but in a qualitatively unique way (15).
VEGF165 Binding (affinity) of
8) Confidence 0.35 Published 2010 Journal American Journal of Physiology - Lung Cellular and Molecular Physiology Section Body Doc Link PMC2886605 Disease Relevance 0.12 Pain Relevance 0
This suggests that sem3A may be secreted by a healthy disc cell and then bind to a NRP-1 molecule on the same cell or a neighbouring cell.
NRP-1 molecule Binding (bind) of
9) Confidence 0.31 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875625 Disease Relevance 0.16 Pain Relevance 0
We thus tested both scenarios: adding a new interaction between VEGF121 and NRP1 at a dissociation constant 1.83 times higher than our control Kd for VEGF165 and NRP1 (to match the Kd ratio measured by Pan et al.); and setting NRP1 affinities for both VEGF isoforms to the exact values as Pan et al. reported.
NRP1 Binding (affinities) of
10) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Among the major endothelial cell surface receptor targets for these VEGF isoforms are: the tyrosine kinases VEGFR1 (Flt-1; UniProt accession P17948-1) and VEGFR2 (mouse Flk-1; human KDR; UniProt accession P35968); as well as the co-receptor neuropilin-1 (NRP1; UniProt accession O14786), which couples directly with VEGFR1, and indirectly with VEGFR2 through non-overlapping binding sites on VEGF165 [7].


neuropilin-1 Binding (tyrosine) of in endothelial cell
11) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0.42 Pain Relevance 0.03
We thus tested both scenarios: adding a new interaction between VEGF121 and NRP1 at a dissociation constant 1.83 times higher than our control Kd for VEGF165 and NRP1 (to match the Kd ratio measured by Pan et al.); and setting NRP1 affinities for both VEGF isoforms to the exact values as Pan et al. reported.
NRP1 Binding (interaction) of
12) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
On the other hand, the overall rise in “pro-angiogenic potential”, as represented by ligated VEGFR2 complexes, can be explained by NRP1's role as a co-receptor in presenting NRP1-bound VEGF165 to VEGFR2, as well as in stabilizing VEGF165-VEGFR2 through their triplet configuration.
VEGF165 Binding (stabilizing) of
13) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
We have previously developed several computational models of the in vivo biochemical interactions between VEGF121, VEGF165, VEGFR1, VEGFR2, NRP1, and the interstitial matrix in skeletal muscle, including: a spatially-averaged single-tissue model of the human vastus lateralis muscle at rest [54]; and several 3D models for predicting spatial molecular gradients and intra-muscular pro-angiogenic treatment outcomes in resting and exercising rat extensor digitorum longus muscle [55]–[58].
VEGF165 Binding (interactions) of in extensor digitorum longus
14) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0.30 Pain Relevance 0
VEGFRs' affinities for VEGF affected free sVEGFR1 concentrations via NRP1 availability; NRP1's affinity for VEGF121 was inconsequential
NRP1 Binding (availability) of
15) Confidence 0.31 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Specifically, when modeling both VEGF121- and VEGF165-affinities of NRP1 at the low affinities cited by Pan et al. (220 nM and 120 nM respectively [105]), there were no remarkable changes in signaling profiles (Fig. 6D) nor concentrations of free soluble species (Fig. 6E) compared to simulation results with no VEGF121-NRP1 binding but weak VEGF165-NRP1 binding.
NRP1 Binding (binding) of
16) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Curly brackets contain the terms referring to the direct binding interaction between VEGF121 and NRP1, which were turned off (kon?
NRP1 Binding (interaction) of
17) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
In the blood, both VEGF121 and VEGF165 were 23% free and 77% bound to sVEGFR1 (Fig.
VEGF165 Binding (bound) of in blood
18) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
The directional change in free sVEGFR1 thus followed that of VEGFR2-VEGF165-NRP1 complexes (Fig. 6A) – i.e., the more VEGFR2-VEGF165-NRP1 complexes formed, the less unbound NRP1 available for binding and internalization of free sVEGFR1 (Fig. 6C).

4.2.

NRP1 Binding (binding) of
19) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0
Specifically, when modeling both VEGF121- and VEGF165-affinities of NRP1 at the low affinities cited by Pan et al. (220 nM and 120 nM respectively [105]), there were no remarkable changes in signaling profiles (Fig. 6D) nor concentrations of free soluble species (Fig. 6E) compared to simulation results with no VEGF121-NRP1 binding but weak VEGF165-NRP1 binding.
NRP1 Binding (binding) of
20) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2663039 Disease Relevance 0 Pain Relevance 0

General Comments

This test has worked.

Personal tools
Namespaces

Variants
Actions
Navigation
Toolbox