• KSBB Journal
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• v.24 no.5
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• pp.425-431
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• 2009

Hepatocyte growth factor (HGF) and its receptor play an important role in the formation and progression of glioma. In this study, I investigated the ability of HGF to recover of the PSA siRNA-suppressed cell proliferation, migration and invasion in U-251-MG cells. PSA siRNA-transfected U-251-MG cells showed the reduction of the proliferation, migration and invasion with compared to control. Treatment of HGF on the PSA siRNA-transfected U-251-MG cells recovered the ability of proliferation, migration and invasion. These data suggest that PSA and HGF may use unique and parallel signaling cascade leading to the proliferative, migrative and invasive phenotype of U-251-MG cells. I also showed that PSA cooperated with HGF to a migrative and invasive phenotype via the increased secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.6
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• pp.636-642
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• 2007

Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.873-876
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• 2013

Our aim was to test the hypothesis that preoperative serum levels of matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) levels correlate with pathological features. Serum levels of MMP-7, and MMP-9 and TIMP-1 were determined in 90 bladder cancer patients and 40 healthy controls using an enzyme linked immunosorbent assay. Preoperative serum MMP-7 and MMP-9 levels were significantly higher in cancer patients than control groups (p<0.001). In contast, serum TIMP-1 levels were lower (p<0.001). Alteration in MMP-7, and MMP-9, and TIMP-1 production may contribute to tumor angiogenesis and be associated with clinic-pathological features.

• Preventive Nutrition and Food Science
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• v.20 no.3
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• pp.153-161
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• 2015

Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that have important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Marine plants are on the rise for their potential to provide natural products that exhibit remarkable health benefits. In this context, brown algae species have been of much interest in the pharmaceutical field with reported instances of isolation of bioactive compounds against tumor growth and MMP activity. In this study, eight different brown algae species were harvested, and their extracts were compared in regard to their anti-MMP effects. According to gelatin zymography results, Ecklonia cava, Ecklonia bicyclis, and Ishige okamurae showed higher inhibitory effects than the other samples on MMP-2 and -9 activity at the concentrations of 10, 50, and $100{\mu}g/mL$. However, only I. okamurae was able to regulate the MMP activity through the expression of MMP and tissue inhibitor of MMP observed by mRNA levels. Overall, brown algae species showed to be good sources for anti-MMP agents, while I. okamurae needs to be further studied for its potential to yield pharmaceutical molecules that can regulate MMP-activity through cellular pathways as well as enzymatic inhibition.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.288-292
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• 2011

Objective : Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 have been known to play an important role in secondary inflammatory reaction after spinal cord injury (SCI). The aim of this study was to investigate the expression and activity of MMP-2 and MMP-9 and to determine their relationship with disruption of endothelial blood-barrier after photochemically induced SCI in rats. Methods : Female Sprague-Dawley rats, weighing between 250 and 300 g (aged 8 weeks) received focal spinal cord ischemia by photothrombosis using Rose Bengal. Expressions and activities of MMP-2 and MMP-9 were assessed by Western blot and gelatin zymography at various times from 6 h to 7 days. Endothelial blood-barrier integrity was assessed indirectly using spinal cord water content. Results : Zymography and Western blot analysis demonstrated rapid up-regulation of MMP-9 protein levels in spinal cord after ischemic onset. Expressions and activities of MMP-9 showed a significant increased at 6 h after the photothrombotic ischemic event, and reached a maximum level at 24 h after the insult. By contrast, activated MMP-2 was not detected at any time point in either the experimental or the control groups. When compared with the control group, a significant increase in spinal cord water content was detected in rats at 24 h after photothrombotic SCI. Conclusion : Early up-regulation of MMP-9 might be correlated with increased water content in the spinal cord at 24 h after SCI in rats. Results of this study suggest that MMP-9 is the key factor involved in disruption of the endothelial blood-barrier of the spinal cord and subsequent secondary damage after photothrombotic SCI in rats.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.4
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• pp.212-218
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• 2003

Matrix metalloproteinases (MMPs) play an important role in the normal morphogenesis, maintenance, and repair of matrix and also have important functions in pathologic conditions characterized by excessive degradation of extracellular matrix, such as rheumatoid arthritis, osteoarthritis, periodontitis and in tumor invasion and metastasis. In this study, expression of MMP-1 and -2 mRNA in retrodiscal tissue of the temporomandibular joint (TMJ) was examined and compared with magnetic resonance imaging (MRI) and surgical findings. MMP mRNAs in the retrodiscal tissue samples were detected by reverse transcription - polymerase chain reaction. TMJ internal derangement (ID) was categorized as normal disc position, disc displacement with reduction, early stage of disc displacement without reduction (DDsR) and late stage of DDsR. TMJ osteoarthrosis (OA) was classified with normal, mild and advanced OA. The amount of synovial fluid collection was divided into not detected, small, large and extremely large amount on MR T2-weighted imaging. Perforation and adhesion were examined during open surgery of the TMJ. Six out of 37 samples were excluded because of little amount of extracted total mRNA. MMP-2 mRNA was detected whole joints, and so the MMP-2 mRNA seems to be expressed normally in retrodiscal tissue. However, MMP-1 mRNA was expressed in 8 of 31 joints. Frequencies of MMP-1 mRNA expression according to the TMJ IDs, amount of synovial fluid and surgical findings made no significant difference. MMP-1 mRNA was detected more frequently in OA groups (7/16 joints, 43.8%) than in normal bony structure group (1/15 joints, 6.7%). Expression of MMP-1 mRNA in retrodiscal tissue might be related with OA of the TMJ.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.32 no.2 s.57
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• pp.117-121
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• 2006

Although many studies have been performed to elucidate the molecular consequence of factors that regulate skin aging, little is known about the effect of green tea catechins except EGCG. The matrix metalloproteinase (MMP), can degrade matrix proteins and results in a collagen deficiency in photodamaged skin, are known to play an important role in photoaging. This study, investigated the effects of green tea catechins on the UVA-induced MMP-1 expression, activity of MMP-2 and synthesis of type I procollagen in human dermal fibroblasts. We examined eight catechins that naturally exist in green tea leaves and compared their efficacies among them. Most of catechins inhibited the expression of MMP-1 in dose dependent manner, and the levels were reduced, especially, 57.4 and 68.2% by treatment with $1{\mu}M$ of epigallocatechin-3-gallate (EGCG) and gallocatechin-3-gallate (GCG), respectively. Also, catechins significantly suppressed the activities of MMP-2. Catechins also induced the expression of type I procollagen, however, they acted only at the concentration below $1{\mu}M$ interestingly. Furthermore, when EGCG:GCG:ECG had the ratio of 0.5:1.5:.1.3, they presented the most effective on procollagen synthesis. Therefore, we concluded that catechins significantly inhibited MMPs and induced collagen synthesis. Taken together, all these results suggested that green tea catechins might be good natural materials act as an anti-photoaging and a skin-aging improving agent.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1105-1110
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• 2014

Objective: Metastases and invasion are the main reasons for oncotherapy failure. Momordica cochinchinensis (Mu Bie Zi in Chinese) had been used for a variety of purposes, and shown anti-cancer action. In this article, we focused on effects on regulation of breast cancer cell ZR-75-30 metastases and invasion by extracts of Momordica cochinchinensis seeds (ESMCs). Methods: Effect of ESMCs on ZR-75-30 human breast cancer cells proliferation were evaluated by MTT assay and on invasion and migration by wound-healing and matrigel invasion chamber assays. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: ESMC revealed strong growth inhibitory effects on ZR-75-30 cells, and effectively inhibited ZR-75-30 cell invasion in a dose-dependent manner. Western blot and gelatin zymography analysis showed that ESMC significantly inhibited the expression and secretion of MMP-2 and MMP-9 in ZR-75-30 cells. Conclusions: ESMC has the potential to suppress the migration and invasion of ZR-75-30 cancer cells, and it might prove to of interest in the development of novel inhibitors for breast cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.3
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• pp.137-145
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• 2009

As an efficient controlled release system for rhBMP-2, a functional nanoparticle-hydrogel complex, incorporated with matrix metalloproteinase(MMP) sensitive peptide cross-linker, was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase(ALP) activity and mineral contents analysis, based on the rat calvarial critical size defect(8mm in diameter) model. Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded MMP sensitive hyaluronic acid(HA) based hydrogel-Nanoparticles(NP) complex, as compared to only MMP HA, the MMP HA-NP without rhBMP-2, or even with the rhBMP-2. These improvements included the formation pattern of bone and functional marrow, the degree of calcium quantification, and the ALP activity. These results indicate that the MMP sensitive HA with nano-particle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced rhBMP-2 scaffold.

• Journal of Life Science
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• v.17 no.7 s.87
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• pp.1019-1022
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• 2007

Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.