INT242569

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Context Info
Confidence 0.55
First Reported 2008
Last Reported 2010
Negated 3
Speculated 0
Reported most in Body
Documents 17
Total Number 17
Disease Relevance 3.61
Pain Relevance 3.54

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

signal transduction (Ret) kinase activity (Ret)
Anatomy Link Frequency
neurons 4
nociceptors 3
sensory neurons 1
sympathetic ganglion 1
IB4 1
Ret (Mus musculus)
Pain Link Frequency Relevance Heat
nociceptor 248 100.00 Very High Very High Very High
Calcitonin gene-related peptide 267 99.34 Very High Very High Very High
Neuropeptide 89 98.70 Very High Very High Very High
Nerve growth factor 358 94.40 High High
dorsal root ganglion 158 90.00 High High
Spinal cord 83 89.80 High High
trigeminal ganglion 14 84.44 Quite High
unmyelinated 48 83.04 Quite High
TRP channel 84 81.44 Quite High
cytokine 12 80.08 Quite High
Disease Link Frequency Relevance Heat
Repression 7 99.74 Very High Very High Very High
Ganglion Cysts 956 98.96 Very High Very High Very High
Nociception 56 97.92 Very High Very High Very High
Targeted Disruption 223 92.76 High High
Sprains And Strains 77 88.88 High High
Hematological Disease 4 78.80 Quite High
Death 90 76.08 Quite High
Apoptosis 100 74.72 Quite High
Embryonic Lethality 2 74.52 Quite High
Neuropathic Pain 19 66.56 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
During late embryonic and early postnatal periods, trkA-expressing neurons differentiate into two subpopulations of nociceptive neurons; trkA-retaining peptidergic neurons, and non-peptidergic neurons that repress trkA and instead activate Ret, a receptor for glial-derived neurotrophic factor (GDNF; Figure 1b).
Positive_regulation (activate) of Ret in peptidergic neurons associated with nociception
1) Confidence 0.55 Published 2008 Journal Neural Develop Section Body Doc Link PMC2531103 Disease Relevance 1.00 Pain Relevance 0.28
On the other hand, Runx1 is essential for the late repression of trkA and induction of Ret when TrkA+ and Ret+ neurons segregate (Figure 1b) [34].
Positive_regulation (induction) of Ret in neurons associated with repression
2) Confidence 0.55 Published 2008 Journal Neural Develop Section Body Doc Link PMC2531103 Disease Relevance 0.65 Pain Relevance 0.28
The restriction of cholinergic properties to a small subpopulation of neurons that occurs until birth requires ret.



Positive_regulation (requires) of ret in neurons
3) Confidence 0.48 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0 Pain Relevance 0
This, in conjunction with the strong upregulation of RET would suggest that both types of nonpeptidergic genes are controlled by the Runx1 overexpression.
Positive_regulation (upregulation) of RET
4) Confidence 0.42 Published 2009 Journal Stem Cells (Dayton, Ohio) Section Body Doc Link PMC2733376 Disease Relevance 0 Pain Relevance 0.14
Mutational inactivation of ret leads to an almost complete loss of cholinergic markers in newborn sympathetic ganglia
Positive_regulation (inactivation) of ret in sympathetic
5) Confidence 0.40 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0.12 Pain Relevance 0.04
The data show that ret is required for the development of cholinergic sympathetic neurons at advanced developmental stages but not for the induction of ChAT and VAChT expression early during embryonic development.
Neg (not) Positive_regulation (required) of ret in neurons
6) Confidence 0.40 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0.25 Pain Relevance 0
Mutational inactivation of the ret gene affects sympathetic ganglion cell number in a complex manner by altering precursor migration, proliferation and cell survival
Positive_regulation (inactivation) of ret in sympathetic ganglion associated with ganglion cysts
7) Confidence 0.40 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0.68 Pain Relevance 0
Surprisingly, ret transcript levels are unchanged, whereas trkA mRNA levels increase by 37%.
Positive_regulation (increase) of ret transcript
8) Confidence 0.37 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0.30 Pain Relevance 0.16
The large majority (>70%) of the GFRalpha3-positive cells express trkA, CGRP and TRPV1 defining a peptidergic ret-positive nociceptor population in contrast to the larger proportion of non-peptidergic ret-positive nociceptors.
Positive_regulation (population) of ret-positive in nociceptors associated with nociceptor and calcitonin gene-related peptide
9) Confidence 0.35 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0.16 Pain Relevance 0.36
Postnatal loss of trkA in a subset of DRG neurons results in the presence of a large population of small ret-positive, IB4-positive and trkA-negative nociceptors in mature DRG.
Positive_regulation (population) of ret-positive in IB4 associated with nociceptor
10) Confidence 0.35 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0.13 Pain Relevance 0.40
This shows that a Runx transcription factor is part of the signalling pathways for regulating ret expression and in turn prompts the question regarding the intracellular transduction pathways mediating ret and GFL signalling.



Positive_regulation (mediating) of ret
11) Confidence 0.35 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0 Pain Relevance 0.13
The postnatal downregulation of trkA in these cells to form ret-positive trkA-negative non-peptidergic nociceptors in turn requires ret.
Positive_regulation (requires) of ret in nociceptors associated with nociceptor
12) Confidence 0.35 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0 Pain Relevance 0.38
The observation suggests that ret signalling is not required for the generation of a TRPV1-positive nociceptor subclass but for the expression of an additional differentiation marker, TRPA1.
Neg (not) Positive_regulation (required) of ret in nociceptor associated with nociceptor
13) Confidence 0.35 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0 Pain Relevance 0.45
No cell loss is detected after counting the cells of dissociated ganglia, leading the authors to conclude that ret is not required for cell viability.
Neg (not) Positive_regulation (required) of ret in ganglia
14) Confidence 0.35 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0.07 Pain Relevance 0.21
Specifically, we could observe upregulation of P2X3 in the transplants arguing that RET-independent markers are induced via the Runx1 pathway.
Positive_regulation (induced) of RET-independent
15) Confidence 0.30 Published 2009 Journal Stem Cells (Dayton, Ohio) Section Body Doc Link PMC2733376 Disease Relevance 0 Pain Relevance 0.20
Thus Runx3 acts to diversify an Ngn1-independent neuronal cohort by promoting the differentiation of proprioceptive sensory neurons, whereas Runx1 controls neuronal diversification within Ngn1-dependent TrkA+ neurons by repression of the neuropeptide Calcitonin gene-related peptide (CGRP)-expressing phenotype and induction of a Ret-expressing phenotype (1–3).
Positive_regulation (induction) of Ret in sensory neurons associated with repression, neuropeptide and calcitonin gene-related peptide
16) Confidence 0.18 Published 2010 Journal Upsala Journal of Medical Sciences Section Body Doc Link PMC2853355 Disease Relevance 0.23 Pain Relevance 0.20
GFRalpha3-positive DRG neurons constitute a population of trkA and ret-positive peptidergic afferents.
Positive_regulation (population) of ret-positive in neurons
17) Confidence 0.18 Published 2008 Journal Cell Tissue Res Section Body Doc Link PMC2516536 Disease Relevance 0 Pain Relevance 0.32

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