Disease relevance of MMP9

• A full-length canine MMP-9 cDNA was cloned from the adenocarcinoma tissue by reverse transcription-PCR and 5'- and 3'-RACE [1].
• The 92 kDa type VI collagenase (matrix metalloproteinase-9 (MMP-9)) activities on zymography assay were found to be 1-6 times higher in benign tumor breast tissues of 12 canines and 4-26 times higher in adenocarcinoma breast tissues of nine canines than that of control tissues, respectively [1].
• Increased expression of MMP-2, MMP-9 (type IV collagenases/gelatinases), and MT1-MMP in canine X-linked Alport syndrome (XLAS) [2].
• METHODS AND RESULTS: We measured hemodynamics, LV function, MMP-2 and MMP-9, and TIMP-3 and TIMP-4 in the ischemic zone (IZ) and nonischemic zone (NIZ) after in vivo IR (90 minutes anterior ischemia; 120 minutes reperfusion) in 28 dogs that were randomized to sham, IR controls, and IR plus the ARB valsartan [3].
• In controls, IR induced LV dysfunction, infarction, and IZ remodeling; increased MMP-9 and decreased TIMP-3 in the IZ compared with the NIZ (low TIMP-3/MMP-9 ratio); and did not change MMP-2 or TIMP-4 [3].

High impact information on MMP9

• Upregulation of MMP-9 in MDCK epithelial cell line in response to expression of the Snail transcription factor [4].
• Myocardial MMP-9 and MMP-13 levels by immunoblot increased with chronic pacing relative to controls (130 +/- 10% and 118 +/- 6%, P < 0.05) and was normalized by TNF block [5].
• A DNA fragment of 1894 bp was isolated and on analysis demonstrated regions of sequence homology with the MMP-9 promoter sequences already determined for other species [6].
• The 5' untranslated region was obtained by genome walking upstream of the canine MMP-9 translation start site using canine genomic DNA as template [6].
• CONCLUSION: Valsartan-induced cardioprotection after IR is associated with enhanced TIMP-3 expression and improved TIMP-3/MMP-9 balance in the in vivo dog model [3].

Biological context of MMP9

• Clinicopathologic features of the disease were characterized, and kidneys from normal and Alport dogs were analyzed by gelatin zymography, Western blotting, in situ zymography, immunohistology, and by reverse transcription polymerase chain reaction (RT-PCR) for expression of MMP-2, MMP-9, and membrane type 1-MMP (MT1-MMP) [2].
• Inhibition of ERK-1/2 activation blocked arterialization-induced upregulation of MMP-2, MMP-9, and MT1-MMP [7].
• METHODS AND RESULTS: Cardiac lymph and tissue were assayed for atent and active MMP-2 and MMP-9 by zymography and immunochemistry [8].
• MMP-2 and MMP-9 in BALF were analysed by zymography, Western immunoblotting and immunocytochemistry.In the PE dogs, BALF, cell count, number and percentage of eosinophils, and numbers of macrophages, lymphocytes, neutrophils, mast cells and epithelial cells were all significantly elevated [9].
• Consistent with their osteoblastic lineage and malignant phenotype, all cell lines were immunoreactive to vimentin, osteopontin, PCNA, p53, MMP-2 and MMP-9, while they were negative for cytokeratin, desmin, SMA, Factor VIII, NSE, GFAP, Rb and p21 protein [10].

Anatomical context of MMP9

• CONCLUSIONS AND CLINICAL RELEVANCE: Data were consistent with results of experimental rodent spinal cord injury studies that indicate that MMP-9 is expressed early during secondary injury [11].
• Additionally, moderate dilation of the rough endoplasmic reticulum and intercalated disk discontinuity were seen after 8 weeks of pacing, and MMP-9 was increased and TIMP-1 was decreased after the same time period [12].
• The neoplastic luminal epithelial cells in 12 malignant tumours reacted strongly for MMP-9 [13].
• The hypothesis tested is that one inflammation-based effector of tissue repair is the secretion and activation of MMP-9 by infiltrating neutrophils [8].
• In contrast, MMP-9 in the myocardium was in both latent and active forms [8].

Associations of MMP9 with chemical compounds

• In the remaining three benign tumours (mixed or complex) MMP-9 expression was observed in the neoplastic luminal epithelial cells and myoepithelial cells in some areas [13].

Other interactions of MMP9

• Gelatin zymography revealed increases in 92-kDa MMP-9 activity and 86-kDa MMP-9 activity at the LV pacing site relative to the remote site, whereas MMP-2 activity was unaffected [14].
• The induction of these MMPs likely contributes to tissue destruction associated with the fibrogenic process, while augmenting the activation of MMP-2 and MMP-9 by MMP-3 and MMP-7 in XLAS [15].
• We characterized the role of inflammatory mediators and extracellular signal-regulated kinases (ERKs) in the control of arterialized vein graft expression of MMP-9, MMP-2, and membrane-type 1-MMP (MT1-MMP) and of the tissue inhibitor of metalloproteinases-2 (TIMP-2) [7].
• Recently, we demonstrated that the expression of MMP-2, MMP-9 and MMP-14 was upregulated in the renal cortex of dogs with a spontaneous form of XLAS [15].
• Similar to MMP-9, expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin S was only found in stifle tissues from dogs with ruptured CCL; in contrast, expression of cathepsin K was found in all ruptured and intact CCL [16].

Analytical, diagnostic and therapeutic context of MMP9

• No significant difference in hospitalization time was detected in dogs with IVDD between those with and without activity of MMP-9 in the CSF [11].
• Compared with the control group, MMP-9 was significantly higher (0.217 +/- 2.16 E-02 vs. 0.314 +/- 5.263 E-02; p < 0.001), while TIMP-1 was decreased (0.230 +/- 8.944 E-02 vs. 0.120 +/- 9.258 E-03; p < 0.001) [12].
• The results indicated that MMP-9 plays an important role in the progression of a canine mammary tumor and that assay of serum MMP-9 is helpful for early diagnosis as progress of adenocarcinoma [1].
• We used electron microscopy and immunoconfocal (IF) labeling for bFGF, matrix metalloproteinase (MMP)-2, MMP-9, tissue-type plasminogen activator (tPA), its inhibitor (PAI-1), fibronectin (FN), and Ki-67 [17].
• Zymography and densitometry showed that expression of MMP-9 was higher in the benign mammary tumours than in normal canine mammary tissues, but highest in the malignant mammary tumours [13].

References