INT234930

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Context Info
Confidence 0.48
First Reported 2008
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 25
Total Number 26
Disease Relevance 20.73
Pain Relevance 0.44

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

cell adhesion (Dsg3) plasma membrane (Dsg3)
Anatomy Link Frequency
keratinocyte 5
epidermis 3
plaque 2
Th2 cells 1
Dsg3 (Mus musculus)
Pain Link Frequency Relevance Heat
imagery 24 86.24 High High
Kinase C 286 77.92 Quite High
addiction 44 68.68 Quite High
metalloproteinase 132 17.52 Low Low
agonist 110 5.00 Very Low Very Low Very Low
corticosteroid 46 5.00 Very Low Very Low Very Low
Pain 24 5.00 Very Low Very Low Very Low
Inflammatory mediators 22 5.00 Very Low Very Low Very Low
antagonist 22 5.00 Very Low Very Low Very Low
cINOD 2 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Bullous Skin Disease 6886 100.00 Very High Very High Very High
Adhesions 1176 100.00 Very High Very High Very High
Acantholysis 1450 99.12 Very High Very High Very High
Skin Diseases 116 98.68 Very High Very High Very High
Disease 446 95.76 Very High Very High Very High
Monilethrix 2 95.40 Very High Very High Very High
Blister 344 94.16 High High
Autoimmune Disease 98 92.32 High High
Streptococcus Infection 46 85.28 High High
Skin Infection 98 82.48 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Given that homophilic interactions between desmosomal cadherins might occur in vivo, it is also possible that DSG3-DSG3 interactions alone might be sufficient to maintain cell adhesion in the Dsc3 null mucosa.
DSG3-DSG3 Binding (interactions) of associated with adhesions
1) Confidence 0.48 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2879910 Disease Relevance 0.46 Pain Relevance 0
In the case of DSG3, it had originally been speculated that a DSG3-DSC3 complex might be essential to maintain keratinocyte adhesion in the deep layers of stratified epithelia (for an alternative view see [6]).
DSG3-DSC3 Binding (complex) of in keratinocyte associated with adhesions
2) Confidence 0.48 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2879910 Disease Relevance 0.63 Pain Relevance 0
These data indicate that PV-IgG and PF-IgG can reduce binding of Dsg 1 and Dsg 3, at least on the keratinocyte cell surface.
Dsg 3 Binding (binding) of in keratinocyte associated with bullous skin disease
3) Confidence 0.25 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.79 Pain Relevance 0
Similarly, homophilic binding of Dsg 3 was found (Amagai et al. 1994b).
Dsg 3 Binding (binding) of
4) Confidence 0.25 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0 Pain Relevance 0
Therefore, it is possible that direct inhibition as a second pathway to reduce Dsg 3 binding in PV may explain the more severe phenotype of PV.
Dsg 3 Binding (binding) of associated with bullous skin disease
5) Confidence 0.25 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 2.31 Pain Relevance 0.11
These autoantibodies induced keratinocyte dissociation and reduced binding of both Dsg 3- and Dsg 1-coated microbeads to the surface of cultured keratinocytes, as revealed by laser trapping (Heupel et al. 2007; Waschke et al. 2005).
Dsg 3 Binding (binding) of in keratinocyte
6) Confidence 0.25 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.82 Pain Relevance 0
Recently, it has been shown that PV- and PF-IgG-induced epidermal splitting, keratinocyte dissociation, as well as loss of Dsg 1 and Dsg 3 binding in vitro were accompanied by p38MAPK-dependent inactivation of Rho A and that specific activation of Rho A by the bacterial toxin cytotoxic necrotizing factor y (CNFy) abolished these effects (Spindler et al. 2007; Waschke et al. 2006).
Dsg 3 Binding (binding) of in keratinocyte associated with bullous skin disease
7) Confidence 0.25 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.75 Pain Relevance 0
This disorder is generally characterized by the production of pathogenic antibodies targeting different components of cell-cell adhesion, in particular, Dsg1 and Dsg3.
Dsg3 Binding (characterized) of associated with adhesions
8) Confidence 0.23 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902105 Disease Relevance 1.37 Pain Relevance 0
In pemphigus foliaceus (PF), patients develop pathogenic autoantibodies that target Dsg1 and promote cell-cell disadhesion in the superficial epidermis, where Dsg1 is highly expressed, but which lacks Dsg3 and Dsg2.
Dsg3 Binding (lacks) of in epidermis associated with bullous skin disease
9) Confidence 0.23 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902105 Disease Relevance 1.76 Pain Relevance 0
According to this concept, in healthy epidermis Dsg 3 binding results in inhibition of glycogen synthase kinase 3 (GSK3) via activation of phosphatidylinositol trisphosphate kinase (PI3K) and Akt.
Dsg 3 Binding (binding) of in epidermis
10) Confidence 0.22 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.29 Pain Relevance 0.03
In PV, when only Dsg 3 antibodies are present, no epidermal blistering would occur because Dsg 1 is considered to compensate for autoantibody-induced loss of Dsg 3 binding.
Dsg 3 Binding (binding) of associated with bullous skin disease
11) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.89 Pain Relevance 0
In PV, epidermal involvement would occur only when autoantibodies against both Dsg 1 and Dsg 3 are present because Dsg 1 is found in all epidermal layers and could compensate for loss of Dsg 3 binding when antibodies to Dsg 3 are solely presentFig. 10Immunostaining of Dsg 1 and Dsg 3 in PV lesional epidermis.
Dsg 3 Binding (binding) of in epidermis associated with bullous skin disease
12) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.00 Pain Relevance 0
Finally, it has to be noted that, if direct inhibition occurs, it is not possible to discriminate at present whether interference with Dsg 3 binding in PV was mediated by steric hindrance, i.e. by blocking trans-interaction of desmoglein molecules by the bound autoantibody, or rather by allosteric effects, i.e. autoantibody-induced conformational changes of the Dsg 3 ectodomain, which in turn interfere with Dsg 3 transinteraction.
Dsg 3 Binding (binding) of associated with bullous skin disease
13) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.52 Pain Relevance 0
Together with the recent finding that AK 23 similar to Dsg 3 antibodies from PV patients, which are known to be also primarily directed against the N-terminal part of EC 1 (Sekiguchi et al. 2001), is able to directly interfere with Dsg 3 binding (Heupel et al. 2007), these data demonstrate that interaction of EC 1 is crucial for Dsg 3 binding.
Dsg 3 Binding (binding) of associated with bullous skin disease
14) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.57 Pain Relevance 0.04
The fact that AK 18 and AK 9, which were directed to the middle and the carboxyterminal parts of the Dsg 3 ectodomain, were not pathogenic and did not directly interfere with Dsg 3 binding suggests that these specific antibodies were not capable of causing allosteric hindrance (Heupel et al. 2007; Tsunoda et al. 2003).
Dsg 3 Binding (binding) of
15) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.23 Pain Relevance 0
An active PV mouse model in which Dsg 3-deficient mice were immunized with Dsg 3 before splenocytes from these animals were transferred to lymphopenic Rag-2-deficient mice supported the notion that Dsg 3 antibodies alone can cause mucosal erosions (Amagai et al. 2000b).
Dsg 3 Binding (immunized) of associated with bullous skin disease
16) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.68 Pain Relevance 0
The fact that AK 18 and AK 9, which were directed to the middle and the carboxyterminal parts of the Dsg 3 ectodomain, were not pathogenic and did not directly interfere with Dsg 3 binding suggests that these specific antibodies were not capable of causing allosteric hindrance (Heupel et al. 2007; Tsunoda et al. 2003).
Dsg 3 Neg (not) Binding (interfere) of
17) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.23 Pain Relevance 0
Together with the recent finding that AK 23 similar to Dsg 3 antibodies from PV patients, which are known to be also primarily directed against the N-terminal part of EC 1 (Sekiguchi et al. 2001), is able to directly interfere with Dsg 3 binding (Heupel et al. 2007), these data demonstrate that interaction of EC 1 is crucial for Dsg 3 binding.
Dsg 3 Binding (binding) of associated with bullous skin disease
18) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.49 Pain Relevance 0.04
Interestingly, to trigger Dsg-induced signalling, autoantibody-mediated cross-linking of Dsg 3 and Dsg 1 seems not to be required because monovalent Fab fragments and single-chain variants of PV- and PF-IgG were effective to cause skin blistering in vivo and to disrupt the desmosomal plaque in vitro (de Bruin et al. 2007; Ishii et al. 2008; Payne et al. 2005; Rock et al. 1990).
Dsg 3 Binding (cross) of in plaque associated with bullous skin disease
19) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.69 Pain Relevance 0.07
Interestingly, endocytosis and depletion of Dsg3 are increasingly recognized to contribute to pemphigus acantholysis (Calkins et al. 2006; Yamamoto et al. 2007a).
Dsg3 Binding (recognized) of associated with acantholysis and bullous skin disease
20) Confidence 0.19 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.69 Pain Relevance 0

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