INT48993

Context Info Confidence 0.57 First Reported 1995 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 17 Total Number 17 Disease Relevance 6.02 Pain Relevance 4.12

endosome (Cftr) transport (Cftr) ATPase activity (Cftr) enzyme binding (Cftr) protein complex (Cftr) transmembrane transport (Cftr)

Anatomy Link Frequency bile 3 ileum 1 glands 1 Cftr (Mus musculus)

Pain Link Frequency Relevance Heat fibrosis 405 100.00 Bile 212 100.00 substance P 18 99.98 qutenza 2 99.76 adenocard 1 99.76 Inflammation 89 93.08 sodium channel 28 87.76 COX-2 inhibitor 1 87.32 agonist 7 81.72 aspirin 30 78.04

Disease Link Frequency Relevance Heat Cystic Fibrosis 405 100.00 Targeted Disruption 51 100.00 Respiratory Sounds 3 95.24 Airway Obstruction 9 94.72 Pneumonia 22 93.08 Shock 3 92.40 Infection 34 92.12 Sprains And Strains 22 91.12 Cancer 2 90.20 INFLAMMATION 73 89.92

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We found a significant increase in bile acid transport in cftr (-/-) and cftr (+/-) mice.

Positive_regulation (increase) of cftr in bile associated with bile

1) Confidence 0.57 Published 2001 Journal BMC Gastroenterol Section Body Doc Link PMC59644 Disease Relevance 0.69 Pain Relevance 0.62

We found a significant increase in bile acid transport in cftr (-/-) and cftr (+/-) mice.

Positive_regulation (increase) of cftr in bile associated with bile

2) Confidence 0.57 Published 2001 Journal BMC Gastroenterol Section Body Doc Link PMC59644 Disease Relevance 0.69 Pain Relevance 0.63

The most striking observation, in response to CFTR knockdown, was the downregulation of LXR-?

Positive_regulation (response) of CFTR

3) Confidence 0.49 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2864762 Disease Relevance 0.15 Pain Relevance 0.07

The effects of PAR(1) but not PAR(2) depend on generation of prostaglandins and activation of CFTR.

Positive_regulation (activation) of CFTR

4) Confidence 0.48 Published 2007 Journal Am. J. Physiol. Gastrointest. Liver Physiol. Section Abstract Doc Link 17431214 Disease Relevance 0.13 Pain Relevance 0.16

These results indicate that SP mediates local responses to capsaicinoids through a mechanism involving coordinated activation of CFTR and K(+) channels.

Positive_regulation (activation) of CFTR associated with substance p

5) Confidence 0.47 Published 2008 Journal Pflugers Arch. Section Abstract Doc Link 18509672 Disease Relevance 0.20 Pain Relevance 0.42

Total amount of FA increased by 1.5-fold upon CFTR gene disruption (Figure 2).

Positive_regulation (increased) of CFTR gene

6) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2864762 Disease Relevance 0.08 Pain Relevance 0

Cystic fibrosis (CF) mice created by targeted disruption of the murine cystic fibrosis transmembrane conductance regulator gene lack adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretion and exhibit marked intestinal complications secondary to inadequate fluid secretion.

Positive_regulation (disruption) of cystic fibrosis transmembrane conductance regulator gene associated with targeted disruption, fibrosis, adenocard and cystic fibrosis

7) Confidence 0.46 Published 1995 Journal Am. J. Physiol. Section Abstract Doc Link 7534995 Disease Relevance 0.54 Pain Relevance 0.33

Substance P stimulates CFTR-dependent fluid secretion by mouse tracheal submucosal glands.

Positive_regulation (stimulates) of CFTR in glands associated with substance p

8) Confidence 0.44 Published 2008 Journal Pflugers Arch. Section Title Doc Link 18509672 Disease Relevance 0.24 Pain Relevance 0.44

Our studies showed that although LPS induces airway constriction in CFTR-/- and cPLA2?

Positive_regulation (constriction) of CFTR

9) Confidence 0.44 Published 2010 Journal Respir Res Section Body Doc Link PMC2873258 Disease Relevance 0.74 Pain Relevance 0.28

inhibitor, ATK, reduced LPS-induced airway constriction in CFTR -/- mice.

Positive_regulation (induced) of CFTR

10) Confidence 0.44 Published 2010 Journal Respir Res Section Body Doc Link PMC2873258 Disease Relevance 0.42 Pain Relevance 0.18

In this study, proteasome inhibitors- LLnL and doxorubicin enhanced the CFTR gene delivery and hence CFTR-mediated short-circuit currents.

Positive_regulation (enhanced) of CFTR gene

11) Confidence 0.43 Published 2010 Journal J Nanobiotechnology Section Body Doc Link PMC2954907 Disease Relevance 0.58 Pain Relevance 0.09

The results from this study indicate that the CFTR is not required for normal sialylation because the BPV cells and WT cells have equivalent sialylation of cytosolic components.

Neg (not) Positive_regulation (required) of CFTR

12) Confidence 0.42 Published 2009 Journal The Open Respiratory Medicine Journal Section Body Doc Link PMC2703207 Disease Relevance 0.16 Pain Relevance 0.04

This led us to explore the mediators involved in the induction of airway constriction in CFTR -/- mice.

Positive_regulation (induction) of CFTR

13) Confidence 0.41 Published 2010 Journal Respir Res Section Body Doc Link PMC2873258 Disease Relevance 0.61 Pain Relevance 0.28

The major difference was, however, noted in the total amount of secreted lipids, which exhibited a 1.8-fold increase in CFTR knockdown cells (Figure 7B).

Positive_regulation (increase) of CFTR

14) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2864762 Disease Relevance 0 Pain Relevance 0

With the cftr gene disruption, there was a 1,5 fold increase in the total FA amount, largely attributable to monounsaturated and saturated FA compared to controls.

Positive_regulation (increase) of cftr gene

15) Confidence 0.40 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2864762 Disease Relevance 0.21 Pain Relevance 0.04

In the ileum, IBAT protein densities and taurocholate uptake rates are elevated in cftr (-/-) mice > cftr (+/-) > wild-type mice.

Positive_regulation (elevated) of cftr in ileum

16) Confidence 0.38 Published 2001 Journal BMC Gastroenterol Section Abstract Doc Link PMC59644 Disease Relevance 0.23 Pain Relevance 0.26

In summary, in the widely studied cftr knockout mouse model (which clearly demonstrates intestinal pathology), the apical sodium dependent ileal bile acid transporter is expressed and functions at higher levels than in wild-type animals, with intermediate levels of IBAT expression and function in heterozygous cftr (+/-) mice.

Positive_regulation (function) of cftr in bile associated with targeted disruption and bile

17) Confidence 0.38 Published 2001 Journal BMC Gastroenterol Section Body Doc Link PMC59644 Disease Relevance 0.35 Pain Relevance 0.29

General Comments

This test has worked.