INT149031

Context Info Confidence 0.75 First Reported 2007 Last Reported 2010 Negated 0 Speculated 3 Reported most in Body Documents 43 Total Number 48 Disease Relevance 19.10 Pain Relevance 2.06

Golgi apparatus (Tjp1) plasma membrane (Tjp1) nucleus (Tjp1) cytoplasm (Tjp1)

Anatomy Link Frequency epithelial cells 4 colon 3 ileum 1 retinas 1 CAR 1 Tjp1 (Mus musculus)

Pain Link Frequency Relevance Heat Nicotine 242 99.14 Spinal cord 41 98.96 Inflammation 382 98.92 agonist 5 91.08 Crohn's disease 104 88.16 anesthesia 46 83.84 noradrenaline 12 73.40 Inflammatory response 29 68.12 tolerance 6 62.88 Central nervous system 20 57.24

Disease Link Frequency Relevance Heat Coronary Artery Disease 6 100.00 Colitis 806 99.46 Injury 37 99.44 Brain Injury 44 99.04 INFLAMMATION 413 98.92 Infection 357 98.84 Lung Cancer 48 98.68 Cancer 288 98.16 Weight Loss 55 97.74 Sprains And Strains 84 97.52

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Whole ileum extracts were used to measure expression of tight junction proteins ZO-1 and occludin by Western blot.

Gene_expression (expression) of ZO-1 in ileum

1) Confidence 0.75 Published 2009 Journal J. Neurotrauma Section Abstract Doc Link 19344293 Disease Relevance 1.06 Pain Relevance 0.08

An increase in intestinal permeability corresponds with decreased expression of tight junction proteins ZO-1 and occludin following TBI.

Gene_expression (expression) of ZO-1 associated with brain injury

2) Confidence 0.75 Published 2009 Journal J. Neurotrauma Section Abstract Doc Link 19344293 Disease Relevance 0.73 Pain Relevance 0.06

We hypothesized that expression of tight junction protein ZO-1 and occludin, responsible for intestinal architectural and functional integrity, will decrease following TBI and increase intestinal permeability.

Gene_expression (expression) of ZO-1 associated with brain injury

3) Confidence 0.75 Published 2009 Journal J. Neurotrauma Section Abstract Doc Link 19344293 Disease Relevance 0.94 Pain Relevance 0.08

Expression of ZO-1 was decreased by 49% relative to sham animals (p < 0.02), whereas expression of occludin was decreased by 73% relative to sham animals (p < 0.001).

Gene_expression (Expression) of ZO-1

4) Confidence 0.75 Published 2009 Journal J. Neurotrauma Section Abstract Doc Link 19344293 Disease Relevance 0.89 Pain Relevance 0.07

Whilst we observed increased expression of Tjp1 at the transcriptional level in NS398 treated infected mice, Jcam expression was not affected.

Gene_expression (expression) of Tjp1

5) Confidence 0.69 Published 2009 Journal Mol Cancer Section Body Doc Link PMC2667483 Disease Relevance 0.32 Pain Relevance 0.09

To analyze whether the improved state of health after EcN treatment is accompanied with an increased ZO-1 expression, IECs were isolated from the colon of treated mice and analyzed for ZO-1 gene expression.

Spec (analyzed) Gene_expression (expression) of ZO-1 in colon

6) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.56 Pain Relevance 0.10

Elevated ZO-1 expression after EcN treatment in experimental colitis

Gene_expression (expression) of ZO-1 associated with colitis

7) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.48 Pain Relevance 0

It can be speculated that the rise of ZO-1 expression results in a reduced intestinal permeability by an enhanced junctional complex or a reinforced interaction of the junctional complex with actin.

Gene_expression (expression) of ZO-1

8) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.61 Pain Relevance 0.04

We demonstrate that EcN specifically up-regulates ZO-1 expression both at the mRNA and at the protein level in IECs of gnotobiotic mice.

Gene_expression (expression) of ZO-1

9) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.91 Pain Relevance 0.09

In addition, we observed an altered ZO-1 expression profile in IECs of mice with DSS-induced colitis.

Gene_expression (expression) of ZO-1 associated with colitis

10) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.75 Pain Relevance 0.08

Together with the influence of EcN on intestinal permeability and an enhanced ZO-1 expression under pathological conditions, it can be speculated that EcN augments mucosal barrier function.

Gene_expression (expression) of ZO-1

11) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.53 Pain Relevance 0

This indicates a considerable association between the severity of colitis, as evidenced by increased gut permeability, and altered ZO-1 mRNA expression levels.

Gene_expression (expression) of ZO-1 mRNA in gut associated with colitis

12) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.62 Pain Relevance 0.04

Therefore, we investigated whether EcN differentially regulates ZO-1 mRNA expression in vivo.

Gene_expression (expression) of ZO-1 mRNA

13) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0 Pain Relevance 0

IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2.

Spec (analyzed) Gene_expression (expression) of ZO-1 in IECs

14) Confidence 0.55 Published 2007 Journal PLoS ONE Section Abstract Doc Link PMC2110898 Disease Relevance 0.67 Pain Relevance 0.09

Using another murine colitis model, administration of n-3 polyunsaturated fatty acids resulted not only in reduced pathological scores but also an increase of ZO-1 protein expression [56].

Gene_expression (expression) of ZO-1 protein associated with colitis

15) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.47 Pain Relevance 0

This report is the first to demonstrate a direct influence of the therapeutic EcN on expression of the TJ associated molecule ZO-1 in vivo under healthy and inflammatory conditions.

Gene_expression (expression) of ZO-1 associated with inflammation

16) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.96 Pain Relevance 0.09

First, EcN is capable of producing a specific up-regulation of ZO-1 expression in IECs of healthy gnotobiotic mice.

Gene_expression (expression) of ZO-1

17) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.37 Pain Relevance 0

To analyze whether the improved state of health after EcN treatment is accompanied with an increased ZO-1 expression, IECs were isolated from the colon of treated mice and analyzed for ZO-1 gene expression.

Gene_expression (expression) of ZO-1 in colon

18) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.67 Pain Relevance 0.10

To further analyze the up-regulated ZO-1 expression at protein level, isolated IECs were investigated by Western blotting.

Spec (analyze) Gene_expression (expression) of ZO-1

19) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0 Pain Relevance 0

It is feasible that the reduction of DSS-mediated downregulation of ZO-1 expression by EcN treatment is one reason for the enhanced barrier stability.

Gene_expression (expression) of ZO-1

20) Confidence 0.55 Published 2007 Journal PLoS ONE Section Body Doc Link PMC2110898 Disease Relevance 0.54 Pain Relevance 0.04

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