• 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.

• Journal of Veterinary Clinics
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• v.18 no.3
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• pp.304-310
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• 2001

The joint disease including osteoarthris (OA) and rheumatoid arthritis (RA) are common in the horse. Many studies have been performed to develop biochemical markers reflecting the abnormalities of cartilage and synovial membrane. However, no specific, sensitive and clinically well established assay systems have been yet available to characterize the severity of joint diseases. Indeed, radiography is still doctor's best choice of assessing joint damage in OA/RA. This review focuses on biochemical molecules such as proteoglycan, collagen, matrix metalloproteinases (MMPs), lectin and cytokine to assess their potential value for not only predicting stage of joint disease but also monitoring treatment efficacy.

• Environmental Analysis Health and Toxicology
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• v.24 no.1
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• pp.63-70
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• 2009

Naringenin, major one of the citrus flavonoids, have been identified that exert antioxidative, anticancer effects. The present study investigated the effects of naringenin on tumor invasion and matrix metalloproteinases(MMPs) activities. Naringenin inhibited cell invasion of HT-1080 fibrosarcoma cells in a dose-dependent manner. The activities of MMP-2 and MMP-9 were inhibited by naringenin as demonstrated by gelatin zymography assay. Furthermore, the amounts of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed in the cells. MMP-2, MMP-9, and MT1-MMP mRNA expression were suppressed by naringenin with time and dose-dependent. These results demonstrate that anti-metastatic activities of naringenin resulted from blocking of invasion of the HT-1080 cells. Taken together, the results of this studies provide evidence that naringenin possess an anti-metastatic activity.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.3
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• pp.201-206
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• 2004

Vascular endothelial growth factor (VEGF), plays a key role in angiogenesis. Many endogenous factors can affect angiogenesis in endothelial cells. VEGF is known to be a strong migration, sprouting, survival, and proliferation factor for endothelial cells during angiogenesis in endothelial cells. Searching for novel genes involved in VEGF signaling during angiogenesis, we carried out differential display polymerase chain reaction on RNA from VEGF-stimulated human umbilical vein endothelial cells (HUVECs). In this study, follistatin (FS) differentially expressed in VEGF-treated HUVECs, compared with controls. Addition of VEGF (10ng/L) produced an approximately 11.8-fold increase of FS mRNA. F5 or VEGF produced approximately 1.8- or 2.9-fold increases, respectively, in matrix metalloproteinase-2 (MMP-2) secretion for 12h, compared to the addition of a control buffer. We suggest that VEGF may affect the angiogenic effect of HUVECs, through a combination of the direct effects of VEGF itself, and the indirect effects mediated via induction of FS in vitro.

• The Plant Pathology Journal
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• v.26 no.4
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• pp.402-408
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• 2010

Plant matrix metalloproteases (MMPs) are a family of apoplastic metalloproteases closely related to human matrilysins. Up-regulation of Nicotiana benthamiana matrix metalloprotease 1 (NMMP1) expression by treatment with pathogens, ethephon and aging indicates that the gene is related to plant defense and the aging process through ethylene signaling. NMMP1 expression was higher than in normal growth leaves following infection with an incompatible pathogen Pseudomonas syringae pv. tomato T1 or a compatible pathogen P. syringae pv. tabaci and in aged leaves. Transient overexpression of NMMP1 in N. benthamiana leaves lowered the growth of P. syringae pv. tabaci. However, NMMP1-silenced leaves showed increased growth of P. syringae pv. tabaci. These data strongly suggest that NMMP1 in N. benthamiana is a defense related gene, which is positively regulated by ethylene.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.177-177
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• 2003

Tumor cell invasion and metastasis are a complex multistep process that involves the degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs). Tissue inhibitor of metalloproteinase-1 (TIMP-1) acts as a negative regulator of matrix metalloproteinase and thus prevents tumor cell invasion and metastasis by preserving extracellular matrix integrity.(omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.168.3-169
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• 2003

The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. Tissue inhibitor of metalloprotease (TIMP)-2, an endogenopus inhibitor of MMP-2, has been shown to inhibit invasion and metastasis. We have previously shown that MMP-2 is responsible for the H-ras-induced invasive and migrative phenotypes in MCF10A human breast epithelial cells. Here, we investigated the effect of TlMP-2 overexpression on invasion and migration in H-ras MCF10A cells. (omitted)

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.1
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• pp.62-66
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• 2022

To date, the development of anticancer drugs has been conducted using two-dimensional (2D) cell culture systems. However, since cancer cells in the body are generated and developed in three-dimensional (3D) microenvironments, the use of 2D anticancer drug screening can make it difficult to accurately evaluate the anticancer effects of drug candidates. Therefore, as a step towards developing a cancer cell-friendly 3D microenvironment based on a combination of vinylsulfone-functionalized polyethylene glycol (PEG-VS) with dicysteine-containing crosslinker peptides with an intervening matrix metalloproteinase (MMP)-specific cleavage site, the types of MMPs secreted from human hepatocarcinoma HepG2 cells, a representative cancer cell, were analyzed transcriptionally and translationally. MMP3 was confirmed to be the most highly expressed protease secreted by HepG2 cells. This knowledge will be important in the design of a crosslinker necessary for the construction of PEG-based hydrogels customized for the 3D culture of HepG2 cells.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.66-74
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• 2003

Purpose : The matrix metalloprotelnases (MMPs) are a family of enzymes whose main function is the degradation of the extracellular matrix. Several studies have revealed that MMPs and TIMPS are related to the wound heating process and in photoaging caused by ultraviolet Irradiation. However, the expressions of MMP and TIMP after irradiation have not, to the best of our knowledge, been studied. This study investigates the expressions of MMP-2 and TIMP-2 in rat Intestinal mucosa following irradiation. Materials and Methods : The entire abdomen of Sprague-Dawley rats was irradiated using a single dose method. The rats were sacrificed on day 1, 2, 3, 5, 7 and 14 following irradiation. Histopathological observations were made using hematoxilin & eosin staining. The expressions of MMP-2 and TIMP-2 were examined using immunohistochemistry, Irnrnunoblotting and ELISA. Results : Radiation induced damage associated with atrophic villi, and infiltration of inflammatory cell was observed from the first postirradiation day, and severe tissue damage was observed on the second and the third postirradiation days. An increase in mitosis and the number of regenerating crypts, as evidence of regeneration, were most noticeable on the fifth postirradiation day. From the immunohistochemlstry, the MMP-2 expression was observed from the first postirradiation day, but was most conspicuous on the third and the fifth postirradiation days. The TIMP-2 expression was most conspicuous on the fifth postirradiation day. From the irnrnunoblotting, the MMP-2 expression was strongly positive on the third postirradlatlon day, and that of TIMP-2 showed a strong positive response on the fifth postirradiation day. In ELISA tests, the expressions of MMP-2 and TIMP-2 were increased in the postirradiation groups compared to those of the normal controls, and showed a maximum increase on the fifth postirradiatlon day. These results were statistically significant. Conclusion : The expressions of MMP-2 and TIMP-2 were increased in the intestinal mucosa of the rats following irradiation, and these results correlated with the histopathological findings, such as tissue damage and regeneration. Therefore, this study suggests that MMP-2 and TIMP-2 play roles in the mechanisms of radiation-induced damage and regeneration of intestinal mucosa of rats.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.420-430
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• 2002

Background : Excessive extracellular matrix (ECM) deposition by airway inflammation is presumed to play an important role in the pathogenesis of worsening airflow obstruction (Ed- acceptable three-word noun) seen during acute exacerbations of chronic bronchitis. Although many proteases can cleave ECM molecules, matrix metalloproteinases (MMPs) and their inhibitors are likely to be the physiologically relevant mediators of ECM degradation. Objectives ; The purpose of this study was to demonstrate that antibiotic treatment can change airway MMPs and TIMP-1 concentrations/levels by controlling airway inflammation in acute exacerbation of chronic bronchitis. Methods : We studied 40 patients, all of whom had an acute exacerbation of chronic bronchitis. The patients were treated with two different antibiotics, moxifloxacin and clarithromycin, in a double-blind manner for 7 days. Sputum samples were induced and collected before and after antibiotic therapy. We measured the sputum concentration of MMP-1,-9, TIMP-1, IL-8 and secretory leukocyte proteinase inhibitor (SLPI) in sputum supernatants by ELISA method. Results : There was no difference after antibiotic treatment in the sputum concentrations of MMP-1,-9, TIMP-1, IL-8 and SLPI between the patients treated with moxifloxacin and those treated with clarithromycin. But the sputum concentrations of TIMP-1, and SLPI, and the TIMP-1/MMP-1 ratio were significantly reduced by the antibiotic therapy. There were significant positive correlations between sputum TIMP-1 levels and IL-8 levels (p<0.01, r=0.751), and between the sputum TIMP-1/MMP-1 ratio and IL-8 levels (p<0.01, r=0.752). The sputum SLPI levels were significantly elevated by antibiotic treatment and were negatively correlated with sputum TIMP-1 levels (p<0.01, r=-0.496) and TIMP-1/MMP-1 levels (p<0.01, r=-0.456). Conclusion : The study shows that the worsening of airway inflammation in acute exacerbation of chronic bronchitis is associated with an imbalance between the concentrations/levels of TIMP-1 and MMPs. Antibiotic treatment can prevent progression of airway narrowing in acute exacerbation of chronic bronchitis by modulation of the protease and anti-protease imbalance.