Disease relevance of Mmp9

• In the present study we investigated the expression of 92-kDa gelatinase (MMP-9) in spinal cord from animals with adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE), using a semiquantitative competitive reverse transcriptase-polymerase chain reaction assay [1].
• Interleukin-1beta (IL-1beta), which is increased in the heart following myocardial infarction, increases expression and activity of MMP-2 (gelatinase A) and -9 (gelatinase B) in cardiac fibroblasts [2].
• Secondary vasogenic edema is maximal 1-2 days after a stroke, which is the time that gelatinase B was elevated [3].
• Our results are compatible with progressive induction of MMP-9 proform, likely in neurons, shortly after ischemia [4].
• The involvement of phosphatidylinositol 3 (PI 3)-kinase in the signalling pathways leading to MMP-9 expression in glioma cells remains unclear [5].

Psychiatry related information on Mmp9

• In organotypic hippocampal cultures, which lack blood cell-mediated inflammation and extrinsic connections, a broad-spectrum inhibitor of MMPs (MMPI), but also a selective MMP-9 inhibitor, protect hippocampal neurons against KA-induced excitotoxicity [6].

High impact information on Mmp9

• PMN depletion simultaneously reduced neutrophil infiltration and MMP-9 levels in lung tissue [7].
• CONCLUSIONS: MMP-9 secretion by PMN can be stimulated by trypsin and proinflammatory cytokines and increases in pancreatitis in proportion to its severity [7].
• Rat renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin-1 beta [8].
• The addition of recombinant glutathione transferase-HuR prevented the rapid decay of MMP-9 mRNA, whereas the addition of a neutralizing anti-HuR antibody caused an acceleration of MMP-9 mRNA degradation [8].
• We demonstrate that NO does strongly destabilize MMP-9 mRNA, since different luciferase reporter gene constructs containing the MMP-9 3' untranslated region (UTR) displayed significant reduced luciferase activity in response to the presence of NO [8].

Chemical compound and disease context of Mmp9

• Taken together, these results suggest that PI 3-kinase may act as a negative regulator of MMP-9 expression in C6 glioma cells [5].
• The purpose of these studies was to evaluate the role of the matrix metalloproteinases MMP-2 and MMP-9 in gastric injury during lipopolysaccharide induced endotoxemia [9].
• Blocking MMP-9 activity with GM6001 significantly attenuated brain extravasation and edema in rats with FHF [10].
• Omeprazole, an established antiulcer drug does not inhibit MMP-9 while protecting indomethacin-induced gastric ulcer [11].
• CONCLUSION: Minocycline inhibits enzymatic activity of gelatin proteases activated by ischemia after experimental stroke and is likely to be selective for MMP-9 at low doses [12].

Biological context of Mmp9

• Apparently the latter effect is based on a reduction in MMP-9 and up-regulation of its inhibitor TIMP-1 [13].
• Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine gene expression of MMP9 and the tissue inhibitors of metalloproteinases TIMP1 and TIMP2 [14].
• v-Ha-RaS oncogene upregulates the 92-kDa type IV collagenase (MMP-9) gene by increasing cellular superoxide production and activating NF-kappaB [15].
• The proto-oncogene, ets-1, is a transcription factor regulating the expression of various matrix proteinases, including MMP-1, MMP-3, and MMP-9 [16].
• Both NF-kappaB and AP-1 DNA were induced in HSC cultured in 3D collagen I gels and binding sites for these factors in the MMP-9 promoter were crucial for induction of transcription [17].

Anatomical context of Mmp9

• Gelatinase B mRNA and protein were localized in macrophages and bronchiolar and alveolar epithelial cells [18].
• Using adult rat cardiac fibroblasts, we show that inhibition of ERK1/2 and JNKs inhibits IL-1beta-stimulated increases in MMP-9, not MMP-2, expression and activity [2].
• Matrix metalloproteinase 9 (MMP-9) degrades basement membrane type IV collagen and is expressed during cellular migration and invasion [15].
• The five cytotoxic lectins decreased the activity of gelatinase B in microglia and of gelatinase A in astrocytes, in a dose-dependent manner [19].
• MMP-2 protein was located in the cell body of neurons, glia, and endothelium, whereas MMP-9 was associated to neurons and myelinated fibre tracts [4].

Associations of Mmp9 with chemical compounds

• To elucidate transcriptional mechanisms for increased gelatinase B expression after hyperoxia, nuclear transcription factor-kappabeta activation was explored [18].
• The Ras-induced increase in NF-kappaB DNA binding could be inhibited by treatment with the antioxidants N-acetyl-L-cysteine and glutathione monoester, suggesting that intracellular oxidant levels can mediate MMP-9 transcription [15].
• Earlier, we showed that lipopolysaccharide (LPS) disrupted the BBB through the action of gelatinase B (MMP-9) [20].
• Using zymography and semi-quantitative RT-PCR analysis, we showed that treatment of C6 cells with wortmannin, an inhibitor of PI 3-kinase activity, potentiated the expression of MMP-9 induced by both cytokines [5].
• Protein levels of tTG and MMP-9 were also analyzed by Western blotting.In situtransglutaminase activity was assayed by measurement of incorporated substrate and the immunofluorescence staining for the cross-linking product, epsilon-(gamma-glutamyl) lysine [21].
• As evidenced by MMP-9 promoter and electrophoretic mobility shift assays, ascofuranone specifically inhibited MMP-9 gene expression by blocking PMA-stimulated activation of activator protein-1 (AP-1) [22].

Physical interactions of Mmp9

• Thus multiple pathways leading to activation of NFkappaB, SP-1, Ets, AP-1, and retinoblastoma binding factors in tumor cells all may contribute to MMP-9 transcription and hence to metastasis [23].

Enzymatic interactions of Mmp9

• At 12 hours, tPA-treated rats showed significantly higher levels of pro-MMP-9 and cleaved MMP-9 than untreated controls [24].

Regulatory relationships of Mmp9

• Semi-quantitative RT-PCR indicated that TNF-alpha also upregulated MMP-9 mRNA levels [25].
• Selective inhibition of PKC-alpha/beta1 using Gö6976 inhibited JNKs activation and the expression and activity of MMP-9, not MMP-2 [2].
• BK-induced MMP-9 mRNA and protein expression was inhibited by MEK1/2 inhibitor PD98059, PI3-K inhibitor LY294002, and NF-kappaB inhibitor helenalin [26].
• ATP potentiates interleukin-1 beta-induced MMP-9 expression in mesangial cells via recruitment of the ELAV protein HuR [27].
• These data indicate a direct correlation between TGF-beta-induced MMP-9 activity and increased endothelial cell permeability [28].

Other interactions of Mmp9

• This effect was specific to MMP-2, because the closely related MMP-9 did not reproduce these changes [29].
• RESULTS: MMP-9, MMP-13, and MMP-14 were expressed in discrete perichondrial cells that gave way to sites of intrachondral canal formation [30].
• An important role of MMP-2, MMP-9, and TIMP-4 in hypertensive remodeling of the cortex and medulla in the SHR is demonstrated [31].
• Induction of myofibroblast MMP-9 transcription in three-dimensional collagen I gel cultures: regulation by NF-kappaB, AP-1 and Sp1 [17].
• Both MMP-9 and TIMP-3 were regulated by various cytokines [32].

Analytical, diagnostic and therapeutic context of Mmp9

• We found that the proteolytic activities of MMP-2 and MMP-9 increased by 2 days after ligation, reached maximal levels at day 10, and remained high through the study period, whereas the gelatinolytic activities in plasma were unchanged [33].
• Glomerular MMP-9 mRNA was reduced 4.6 +/- 0.6-fold (n = 3; p < 0.05), MMP-9 protein was not detectable by Western blotting and MMP-9 activity was considerably suppressed in gelatin zymograms [13].
• Gel mobility shift assays demonstrated that Ras overexpression enhanced NF-kappaB, but not AP-1 DNA binding to motifs in the MMP-9 gene promoter [15].
• Gelatin zymography and Northern blotting were used to confirm induction of MMP-9 protein and mRNA expression in primary rat HSC cultured in a three-dimensional collagen I gel lattice [17].
• Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures [34].

References