• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.21-30
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• 2005

Matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes and implicated in the remodeling and degradation of extracellular matrix under both physiological and pathological conditions. Connective tissue degradation in periodontal diseases is thought to be due to excessive MMP activities over their specific inhibitors. The effects of lipopolysaccharide (LPS) from Prevotella intermedia, one of the major putative pathogens of periodontitis, on the expression of mRNA for MMPs and tissue inhibitors of metalloproteinases (TIMPs) in human gingival and periodontal ligament fibroblasts were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of mRNAs encoding MMP-1, -2, -3, -10, and -14 was increased in human gingival fibroblasts treated with p. intermedia LPS, whereas MMP-11 and TIMP-2 mRNA expression was decreased in these cells stimulated with LPS. P. intermedia LPS increased the MMP-1, -2, -10, -11, and -14 mRNA expression and decreased TIMP-1 and -2 mRNA expression in human periodontal ligament fibroblasts. These findings imply that P. intermedia LPS may play an important role in the connective tissue degradation in periodontitis.

• Preventive Nutrition and Food Science
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• v.14 no.1
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• pp.14-20
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• 2009

Matrix metalloproteinases (MMPs) are a group of zinc proteases that serve the function of breaking down extracellular matrix (ECM). The present study evaluated the role of N-acetylcysteine (NAC) on the increased deposition of ECM in hepatic and glomerular fibrosis caused by carbon tetrachloride ($CCl_4$). The activity of MMPs increased and the levels of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) decreased in the liver and kidney of $CCl_4$-treated rats. Rats treated with $CCl_4$ and NAC showed increased activities of MMPs and decreased levels of TIMP-1 and TIMP-2 in the liver and kidney. Treatment with NAC resulted in the effective degradation of ECM due to an increase in the activities of MMPs and a decrease in the levels of TIMPs.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.133-143
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• 2012

Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are re-sponsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, com-partmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain devel-opment, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer's disease, multiple sclerosis, ischemia/reperfusion and Parkinson's disease. We further highlight accumu-lating evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflamma-tion, apoptosis and degradation of ${\alpha}$-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.

• Journal of Chest Surgery
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• v.44 no.6
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• pp.387-391
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• 2011

Background: The relationship between the degree of expression of matrix metalloproteinases or tissue inhibitor of metalloproteinases and venous reflux remains to be investigated. Materials and Methods: Primary varicose vein tissues were obtained from 23 patients, 18 females and 5 males, aged from 19 to 73. Cephalic or basilic veins were obtained for the control group from 10 patients who underwent vascular access for maintenance hemodialysis. Two operative techniques (high ligation with stripping or endovenous laser coagulation) were used. The expression of matrix metalloproteinase-2 and 13 and tissue inhibitor of metalloproteinase-4 in the varicose vein group and control group was assessed semi-quantitatively by immunohistochemical slides stained with primary antibodies. Results: Twenty (87%) of the varicose vein group patients had greater or lesser saphenous vein diseases with reflux. The focal weak (+) stain for matrix metalloproteinases-2, and 13, and tissue inhibitor of matrix metalloproteinase-4 was dominant in the varicose vein group; the focal or diffuse strong stain (++ or +++) was prevalent in the control group. The differences were statistically significant (p<0.01). The degree of reflux and the duration of symptoms were not significantly related to the expression of MMP-13 (p=0.317 and p=0.654, respectively). Conclusion: Further study should be performed to investigate the relationship between the clinical characteristics related to venous hypertension or reflux and expression of MMPs and TIMP in varicose veins.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3043-3051
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• 2016

Controlled remodeling of the extracellular matrix (ECM) is essential for cell growth, invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of secreted, zinc-dependent endopeptidases capable of degradation of ECM components. The expression and activity of MMPs in a variety of human cancers have been intensively studied. They play important roles at different steps of malignant tumor formation and have central significance in embryogenesis, tissue remodeling, inflammation, angiogenesis and metastasis. However, increasing evidence demonstrates that MMPs are involved earlier in tumorigenesis. Recent studies also suggest that MMPs play complex roles in tumor progression. MMPs and membrane type (MT)-MMPs are potentially significant therapeutic targets in many cancers, so that designing of specific MMP inhibitors would be helpful for clinical trials. Here, we review the pleiotropic roles of the MMP system in hematological malignancies in-vitro and in-vivo models.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3259-3264
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• 2012

Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and $40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

• BMB Reports
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• v.36 no.1
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• pp.128-137
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• 2003

Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, rheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involves a cascade of linked, sequential steps that involve multiple host-tumor interactions. Specifically, MMPs are involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot perform successful metastasis. The activities of MMPs are tightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review.

• Journal of Integrative Natural Science
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• v.4 no.4
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• pp.255-265
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• 2011

Marine ecosystems are often characterized by a high biological diversity, and it corresponds to a high chemical diversity. Up to present, more than 20,000 new bioactive substances have been isolated from marine organisms, where considerable numbers of these naturally occurring derivatives are developed as potential candidates for pharmaceutical application. In this process, screening of natural products from marine organisms that could potentially inhibit the expression of metalloproteinases has gained a huge popularity. Cancer is considered as one of the deadliest diseases in the medical field. Matrix metalloproteinase (MMPs) can degrade extracellular matrix (ECM) components and play important roles in a variety of biological and pathological processes. Matrix metalloproteinase inhibitors (MMPIs) have been identified as potential therapeutic candidates for metastasis, arthritis, chronic inflammation and wrinkle formation.

• Biomedical Science Letters
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• v.20 no.3
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• pp.103-110
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• 2014

Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They are multidomain proteins and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs). The uncontrolled regulation of MMPs is involved in various pathologic processes, such as tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Especially, matrix metalloproteinase-9 (MMP-9) is one of the metastasis-accelerating genes involved in metastasis of various types of human cancers. Here, we review the member of MMP family and discusses their domain structure and function, enzyme activation, the mechanism of inhibition by TIMPs. In particular, we focus the role of MMP-9 in relation to cancer metastasis.

• Proceedings of the Ginseng society Conference
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• 2007.05a
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• pp.25-25
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• 2007