INT89282

Context Info Confidence 0.60 First Reported 2000 Last Reported 2010 Negated 6 Speculated 3 Reported most in Body Documents 39 Total Number 42 Disease Relevance 25.45 Pain Relevance 10.34

peptidase activity (MMP9) extracellular space (MMP9) extracellular region (MMP9) proteinaceous extracellular matrix (MMP9) extracellular matrix organization (MMP9) protein complex (MMP9)

Anatomy Link Frequency cerebrospinal fluid 2 extracellular matrix 2 lung 2 urine 1 joint 1 MMP9 (Homo sapiens)

Pain Link Frequency Relevance Heat metalloproteinase 886 100.00 cytokine 312 100.00 agonist 27 99.82 Angina 43 99.68 corticosteroid 4 99.64 COX-2 inhibitor 70 99.44 Arthritis 129 99.18 Inflammation 402 98.82 Pain 21 98.48 rheumatoid arthritis 96 97.12

Disease Link Frequency Relevance Heat Urological Neuroanatomy 34 99.90 Angina 34 99.68 Herpes Simplex Virus 714 99.64 Fibrosarcoma 20 99.60 Arthritis 130 99.18 INFLAMMATION 456 98.82 Rupture 30 98.68 Arthralgia 5 98.48 Death 46 98.44 Necrosis 36 98.40

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Key:

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Mutation

Event

Anatomy

Negation

Speculation

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Disease term

MMP-9 activity is controlled at different levels: transcriptional activation of the gene by cytokines and other factors, activation of the pro-enzyme by various enzymes like serine proteases and regulation by specific tissue inhibitors of the matrix metalloproteinases (TIMPs).

Regulation (controlled) of MMP-9 associated with metalloproteinase and cytokine

1) Confidence 0.60 Published 2009 Journal Lipids Health Dis Section Body Doc Link PMC2667508 Disease Relevance 0.85 Pain Relevance 0.49

Hence, our data may imply that post-transcriptional regulation of MMP9 prevails over the transcriptional changes as the major control mechanism.

Regulation (regulation) of MMP9

2) Confidence 0.58 Published 2005 Journal BMC Cancer Section Body Doc Link PMC1182358 Disease Relevance 0.30 Pain Relevance 0

Activated MMP1, MMP3 and latent forms of MMP2 and MMP9 are regulated and inhibited by endogenous proteins known as tissue inhibitors of metalloproteinase TIMP1 and TIMP2 [17].

Regulation (regulated) of MMP9 associated with metalloproteinase

3) Confidence 0.55 Published 2006 Journal BMC Urol Section Body Doc Link PMC1560390 Disease Relevance 0.82 Pain Relevance 0.23

PDE4 inhibition reduced cyclooxygenase-2 protein expression and PGE(2) production and also modulated MMP-9, a key mediator of the membrane rupture process, by inhibiting pro-MMP-9 mRNA expression and pro-MMP-9 activity.

Regulation (modulated) of MMP-9 associated with rupture

4) Confidence 0.53 Published 2005 Journal J. Immunol. Section Abstract Doc Link 15944316 Disease Relevance 0.73 Pain Relevance 0.46

Topical corticosteroids might affect the change in MMP-9 activity and CS concentrations and thereby impact corneal wound healing.

Spec (might) Regulation (change) of MMP-9 associated with corticosteroid and wound healing

5) Confidence 0.53 Published 2010 Journal Clinical Ophthalmology (Auckland, N.Z.) Section Body Doc Link PMC2915870 Disease Relevance 0.95 Pain Relevance 0.14

In the present study, sulfated glucosamine (SGlc) that has been reported to relieve joint pain and inflammation in many arthritis patients was studied for its inhibitory effects on MMP-2 and MMP-9 in human fibrosarcoma cells.

Regulation (effects) of MMP-9 in joint associated with pain, fibrosarcoma, arthralgia, inflammation and arthritis

6) Confidence 0.52 Published 2007 Journal Bioorg. Med. Chem. Section Abstract Doc Link 17498959 Disease Relevance 0.47 Pain Relevance 0.20

Given that fibrinogen is a substrate of MMP9 [39–41], it is possible that up regulation of MMP9 and TIMP1 in circulation may be directly associated to the generation of FGA peptide biomarkers that ultimately are enriched in urine during active SJIA.

Regulation (regulation) of MMP9 in urine

7) Confidence 0.49 Published 2010 Journal Clin Proteomics Section Body Doc Link PMC2970804 Disease Relevance 0.63 Pain Relevance 0.21

To determine the effects of OPN levels on MMP-9 activity, conditioned media was collected from four independent clones that express high level of full length OPN (B, lanes 3–6), mutant OPN (B; lanes 7–10) and five independent SiRNA clones (C; lanes 3–7).

Spec (determine) Regulation (effects) of MMP-9

8) Confidence 0.46 Published 2007 Journal Mol Cancer Section Body Doc Link PMC1828067 Disease Relevance 0.43 Pain Relevance 0.03

The lack of a persistent effect on cerebrospinal fluid leucocyte recruitment and MMP-9 activity, despite changes in IgG synthesis, T-cell activation, and cytokine production, suggests that modulation of the function of inflammatory cells may contribute to the clinical efficacy of oral high-dose methylprednisolone treatment in optic neuritis and multiple sclerosis.

Regulation (effect) of MMP-9 in cerebrospinal fluid associated with multiple sclerosis, inflammation, optic neuritis, neuritis and cytokine

9) Confidence 0.41 Published 2000 Journal Eur. J. Neurol. Section Abstract Doc Link 10886311 Disease Relevance 0.78 Pain Relevance 0.65

We further confirmed the expression levels of three up-regulated proteins (MMP-9, DJ-1 and A1BG) in pancreatic juice, tissue and serum samples using Western blot, IHC or ELISA.

Regulation (regulated) of MMP-9

10) Confidence 0.41 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2528014 Disease Relevance 1.26 Pain Relevance 0.16

There are no changes in the surface levels of MMP-9 in PC3 cell lines, and only a single band of MMP-9 protein (85–90 kDa) was detected in all cells (Figure 2C).

Neg (no) Regulation (changes) of MMP-9 in band

11) Confidence 0.40 Published 2007 Journal Mol Cancer Section Body Doc Link PMC1828067 Disease Relevance 0.06 Pain Relevance 0

While MMP-2 activity remains the same, changes in MMP-9 activity was observed in PC3 cell lines.

Regulation (changes) of MMP-9

12) Confidence 0.40 Published 2007 Journal Mol Cancer Section Body Doc Link PMC1828067 Disease Relevance 0.41 Pain Relevance 0.04

Moreover, down-regulation of NF-kappaB resulted in production of low levels of both NF-kappaB p50 and p65 proteins and directly affected activation process of MMP-2 and MMP-9 expressions.

Regulation (affected) of MMP-9

13) Confidence 0.38 Published 2007 Journal Bioorg. Med. Chem. Section Abstract Doc Link 17498959 Disease Relevance 0.44 Pain Relevance 0.22

have been shown to up-regulate matrix metalloproteinase-9 (MMP-9) [7], [8].

Regulation (regulate) of matrix metalloproteinase-9 associated with metalloproteinase

14) Confidence 0.27 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2258002 Disease Relevance 1.05 Pain Relevance 0.31

have been shown to up-regulate matrix metalloproteinase-9 (MMP-9) [7], [8].

Regulation (regulate) of MMP-9 associated with metalloproteinase

15) Confidence 0.27 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2258002 Disease Relevance 1.06 Pain Relevance 0.31

These results were not surprising since the levels of MMP-9 in SF have been shown to vary according to several factors, such as the disease state, the local concentration of inflammatory cytokines, and the number of infiltrating leukocyte subpopulations [24,25].

Regulation (vary) of MMP-9 in leukocyte associated with inflammation, metalloproteinase, disease and cytokine

16) Confidence 0.25 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779417 Disease Relevance 1.26 Pain Relevance 1.01

No effect was seen on the cerebrospinal fluid leucocyte count or the cerebrospinal fluid activity of matrix metalloproteinase-9 (MMP-9).

Neg (No) Regulation (effect) of MMP-9 in cerebrospinal fluid associated with metalloproteinase

17) Confidence 0.25 Published 2000 Journal Eur. J. Neurol. Section Abstract Doc Link 10886311 Disease Relevance 0.62 Pain Relevance 0.63

In this study the concentrations of MMP1, MMP2, MMP3, MMP9, their inhibitors TIMP1, TIMP2, and the MMP1/TIMP1-complex (MTC1) were quantified in blood plasma with the sandwich enzyme-linked immunosorbent assay (ELISA).

Regulation (concentrations) of MMP9 in blood

18) Confidence 0.24 Published 2006 Journal BMC Urol Section Abstract Doc Link PMC1560390 Disease Relevance 0.44 Pain Relevance 0.13

Niranjan et al. studied for SG inhibitory effects on MMP-2 and MMP-9 in human fibrosarcoma cells.

Regulation (effects) of MMP-9 associated with fibrosarcoma

19) Confidence 0.24 Published 2009 Journal Marine Drugs Section Body Doc Link PMC2707034 Disease Relevance 0.56 Pain Relevance 0.24

Plausible pathways of potential interest for MMP-9 regulation such as antioxidant/oxidant imbalance [32], [33] and/or influences of different hormones (stress [34] and sex [35], [36]) should be further investigated.

Regulation (regulation) of MMP-9 associated with stress

20) Confidence 0.23 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2258002 Disease Relevance 0.24 Pain Relevance 0.04

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