INT179659

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Context Info
Confidence 0.52
First Reported 2004
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 13
Total Number 17
Disease Relevance 11.56
Pain Relevance 2.23

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

peptidase activity (Mmp12) extracellular region (Mmp12) proteinaceous extracellular matrix (Mmp12)
Anatomy Link Frequency
macrophage 6
lung 3
alveolar macrophages 2
Th1 cells 1
osteoclasts 1
Mmp12 (Mus musculus)
Pain Link Frequency Relevance Heat
metalloproteinase 426 99.56 Very High Very High Very High
Inflammatory response 31 93.48 High High
Inflammation 785 91.80 High High
antagonist 75 90.00 High High
substance P 55 87.36 High High
fibrosis 85 85.68 High High
Inflammatory mediators 100 78.64 Quite High
chemokine 28 55.36 Quite High
Neuropeptide 2 54.08 Quite High
cytokine 78 49.88 Quite Low
Disease Link Frequency Relevance Heat
Pulmonary Disease 1214 99.60 Very High Very High Very High
Emphysema 221 98.16 Very High Very High Very High
Disease 87 97.56 Very High Very High Very High
Lung Injury 62 96.16 Very High Very High Very High
Pulmonary Emphysema 87 95.04 Very High Very High Very High
INFLAMMATION 707 93.12 High High
Pneumonia 210 91.80 High High
Burns 9 91.68 High High
Nicotine Addiction 143 88.80 High High
Fibrosis 103 85.76 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Signaling through PAR-1 increases macrophage MMP-12 synthesis (Raza et al 2000; Churg et al 2007b).
Gene_expression (synthesis) of MMP-12 in macrophage
1) Confidence 0.52 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 0.58 Pain Relevance 0
Macrophages and DCs are the main sources of MMP-12, a matrix metalloproteinase that has been described as the key proteolytic enzyme in the development of CS-induced emphysema in mice [31].
Gene_expression (sources) of MMP-12 in Macrophages associated with emphysema and metalloproteinase
2) Confidence 0.49 Published 2009 Journal Respir Res Section Body Doc Link PMC2689186 Disease Relevance 0.42 Pain Relevance 0.22
Moreover, immunohistochemical staining showed impaired production of MMP-12 in alveolar macrophages of CS-exposed NK1-R-/- mice.
Gene_expression (production) of MMP-12 in alveolar macrophages
3) Confidence 0.49 Published 2009 Journal Respir Res Section Body Doc Link PMC2689186 Disease Relevance 0.52 Pain Relevance 0.15
Interestingly, the MMP-12 induction upon CS-exposure was significantly attenuated in NK1-R-/- mice, compared to WT mice (Figure 5).


Gene_expression (induction) of MMP-12
4) Confidence 0.48 Published 2009 Journal Respir Res Section Body Doc Link PMC2689186 Disease Relevance 0.37 Pain Relevance 0.15
However, plasmin also cleaves and activates latent growth factors, latent proMMPs, and protease-activated receptor-1 (PAR-1) on macrophages, which drives macrophage MMP-12 production (Saksela and Rifkin 1988; Taipale et al 1992; Raza et al 2000; Churg et al 2007b).
Gene_expression (production) of MMP-12 in macrophage
5) Confidence 0.45 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 0.27 Pain Relevance 0.09
Early studies failed to detect increased expression of MMP-12 in lung samples (Finlay et al 1997; Imai et al 2001), but more recent studies using other techniques have demonstrated increased levels of MMP-12 in human COPD (Grumelli et al 2004; Molet et al 2005; Woodruff et al 2005; Demedts et al 2006).
Gene_expression (expression) of MMP-12 in lung associated with pulmonary disease
6) Confidence 0.45 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 1.14 Pain Relevance 0.18
Chronic CS-exposure revealed significantly increased MMP-12 staining in macrophages of WT mice, compared to air-exposed controls (Figure 5).
Gene_expression (staining) of MMP-12 in macrophages
7) Confidence 0.42 Published 2009 Journal Respir Res Section Body Doc Link PMC2689186 Disease Relevance 0.37 Pain Relevance 0.13
This process may also contribute to COPD pathogenesis in human subjects, since lung tissue from human COPD patients contains increased numbers of Th1 cells associated with increased levels of IP-10 and MMP-12 (Grumelli et al 2004).
Gene_expression (levels) of MMP-12 in Th1 cells associated with pulmonary disease
8) Confidence 0.40 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 0.62 Pain Relevance 0.17
Early studies failed to detect increased expression of MMP-12 in lung samples (Finlay et al 1997; Imai et al 2001), but more recent studies using other techniques have demonstrated increased levels of MMP-12 in human COPD (Grumelli et al 2004; Molet et al 2005; Woodruff et al 2005; Demedts et al 2006).
Gene_expression (levels) of MMP-12 in lung associated with pulmonary disease
9) Confidence 0.39 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 0.95 Pain Relevance 0.11
1-PI inhibiting both PMN serine proteinase-mediated ECM destruction and thrombin- or plasmin-induced increases in macrophage MMP-12 production (Churg et al 2003b, 2007b).


Gene_expression (production) of MMP-12 in macrophage
10) Confidence 0.39 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 0.44 Pain Relevance 0.15
mice exposed chronically to cigarette smoke demonstrated interactions between these two classes of proteinases (Figure 3), with MMP-12 cleaving and inactivating ?
Gene_expression (cleaving) of MMP-12
11) Confidence 0.39 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 1.01 Pain Relevance 0.13
Genetic polymorphisms in matrix metalloproteinase genes MMP1, MMP9 and MMP12 may be important in the development of COPD.
Gene_expression (important) of MMP12 associated with pulmonary disease and metalloproteinase
12) Confidence 0.38 Published 2004 Journal Respir Res Section Body Doc Link PMC533858 Disease Relevance 1.62 Pain Relevance 0.14
Moreover, an impaired production of MMP-12 by alveolar macrophages upon CS-exposure was observed in these KO mice.
Gene_expression (production) of MMP-12 in alveolar macrophages
13) Confidence 0.38 Published 2009 Journal Respir Res Section Abstract Doc Link PMC2689186 Disease Relevance 0.89 Pain Relevance 0.25
Studies of mice genetically deficient in proteinases in these acute exposure models have identified critical roles for MMP-12 in regulating PMN influx and for thrombin and plasmin in regulating MMP-12 production (Figure 2).
Gene_expression (production) of MMP-12
14) Confidence 0.35 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 0.87 Pain Relevance 0.03
inducible protein 10 (IP-10), which induces production of MMP-12 and degradation of the lung ECM (Figures 1 and 3).
Gene_expression (production) of MMP-12 in lung
15) Confidence 0.35 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629972 Disease Relevance 0.63 Pain Relevance 0.15
6-null mice develop age-related emphysema through the loss of activation of latent TGF-beta which leads to an increase in macrophage MMP-12 expression [171].
Gene_expression (expression) of MMP-12 in macrophage associated with emphysema
16) Confidence 0.30 Published 2004 Journal Respir Res Section Body Doc Link PMC533858 Disease Relevance 0.57 Pain Relevance 0
Additionally, MMP-12 produced by osteoclasts or periosteoclastic cells contributes to bone matrix solubilization and osteoclast migration, thereby controlling the cell-matrix interactions that are required for cell attachment/detachment [36].
Gene_expression (produced) of MMP-12 in osteoclasts
17) Confidence 0.14 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2212555 Disease Relevance 0.27 Pain Relevance 0.18

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