• Title, Summary, Keyword: matrix metalloproteinases-9

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Polymorphism, Genetic Effect and Association with Egg Production Traits of Chicken Matrix Metalloproteinases 9 Promoter

  • Zhu, Guiyu;Jiang, Yunliang
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.11
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    • pp.1526-1531
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    • 2014
  • Matrix metalloproteinases (MMP) are key enzymes involved in cell and tissue remodeling during ovarian follicle development and ovulation. The control of MMP9 transcription in ovarian follicles occurs through a core promoter region (-2,400 to -1,700 bp). The aim of this study was to screen genetic variations in the core promoter region and examine MMP9 transcription regulation and reproduction performance. A single cytosine deletion/insertion polymorphism was found at -1954 $C^+/C^-$. Genetic association analysis indicated significant correlation between the deletion genotype ($C^-$) with total egg numbers at 28 weeks (p = 0.031). Furthermore, luciferase-reporter assay showed the deletion genotype ($C^-$) had significantly lower promoter activity than the insertion genotype ($C^+$) in primary granulosa cells (p<0.01). Therefore, the identified polymorphism could be used for marker-assisted selection to improve chicken laying performance.

Roles of Matrix Metalloproteinase-9 in Cancer Metastasis

  • Kang, Hyereen;Jang, Sung-Wuk
    • 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.

Curcumin Effect on MMPs and TIMPs Genes in a Breast Cancer Cell Line

  • Hassan, Zeinab Korany;Daghestani, Maha Hassan
    • 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.

The Potential Roles of Cyclooxygenase-2 and Matrix Metalloproteinase-9 in Cytomegalovirus-Infected Atherosclerotic Aorta and Coronary Artery

  • Eom, Yong-Bin
    • Biomedical Science Letters
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    • v.9 no.3
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    • pp.123-131
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    • 2003
  • Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study hypothesized that a vascular infection with cytomegalovirus (CMV) may induce a chronic inflammatory reaction and activated inflammatory cells may express inflammatory mediators such as cyclooxygenase-2 (COX-2) and matrix metalloproteinases-9 (MMP-9). To confirm the hypothesis, the immunohistochemical stains for CMV late antigen, COX-2, MMP-9, macrophage, and T-lymphocyte were performed on CMV-infected atherosclerotic lesions. The immunoreactivity for COX-2 and MMP-9 was evident in all cases of atherosclerosis along with plaques, mainly in macrophages/foamy cells, intimal and medial smooth muscle cells, and endothelial cells of the intima. Within the intima, the increased immunoreactivity for COX-2 and MMP-9 was colocalized to the area stained with CMV late antigen. Sections from control specimens showed no immunoreactivity for CMV late antigen, COX-2 and MMP-9. These data seem to support the hypothesis that CMV may participate in a pathogenetic mechanism for atherogenesis or progression of atherosclerosis.

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Matrix Metalloproteinase: Inhibitory Effect of Marine Substances on MMP-2 and MMP-9

  • Nguyen, Van-Tinh;Qian, Zhong-Ji;Jung, Won-Kyo
    • Journal of the Chosun 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.

Platelet-Activating Factor Enhances Experimental Pulmonary Metastasis of Murine Sarcoma Cells by Up-regulation of Matrix Metalloproteinases-9 Through NF-$\kappa$B-Dependent Pathway

  • Ko, Hyun-Mi;Back, Hae-Kyong
    • Biomedical Science Letters
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    • v.10 no.2
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    • pp.143-151
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    • 2004
  • Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, a process that is necessary for angiogenesis, tumor invasion and metastasis. Platelet-activating factor (PAP) increases angiogenesis, tumor growth and metastasis through nuclear factor (NF)-$\kappa$B activation. Based on these facts, the involvement of MMPs in PAF-induced pulmonary metastasis was investigated in murine sarcoma cells, MMSV-BALB/3T3. Messenger RNA expression and enzymatic activity of MMP-9 were assessed by RT-PCR and zymography, and cell migration and metastasis were done for the detection of MMP-9 functional activity. PAP induced mRNA expression and enzymatic activity of MMP-9, and its effects were either inhibited by the PAP antagonist, WEB 2170 or by the NF-$\kappa$B inhibitor, parthenolide, or p65 antisense oligonucleotide in a dose-dependent manner. In addition, PAF induced promoter activity of MMP-9, which was inhibited by WEB 2170, phenanthroline, NAC, PDTC. These results indicate that PAF induces mRNA expression and enzymatic activity of MMP-9 in NF-$\kappa$B dependent manner. Cell migration assay showed that PAF induced MMSV-BALB/3T3 migration, and its effect was significantly inhibited by treatment with phenanthroline. PAF enhanced pulmonary metastasis of murine sarcoma cells, MMSV-BALB/3T3 was also reduced by phenanthroline. These results suggest that PAF-enhanced cell migration and pulmonary metastasis is mediated through the expression of MMP. In conclusion, It is suggested that PAF enhances pulmonary metastasis by inducing MMP-9 expression via the activation of NF-$\kappa$B.

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Genistein Suppresses TPA-Induced Matrix Metalloproteinases Activity and Cell Invasion in Human Breast Adenocarcinoma Cells (인체 유방암세포에서 TPA에 의해 유도된 matrix metalloproteinases 활성 및 침윤성 증대에 미치는 genistein의 영향)

  • Choi, Yung-Hyun;Kim, Sung-Ok
    • Journal of Life Science
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    • v.22 no.7
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    • pp.964-969
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    • 2012
  • Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

Activation of Matrix Metalloproteinases-9 after Photothrombotic Spinal Cord Injury Model in Rats

  • Jang, Jae-Won;Lee, Jung-Kil;Kim, Soo-Han
    • 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.

Abalone Haliotis discus hannai Intestine Digests with Different Molecule Weights Inhibit MMP-2 and MMP-9 Expression in Human Fibrosarcoma Cells

  • Nguyen, Van-Tinh;Qian, Zhong-Ji;Jung, Won-Kyo
    • Fisheries and aquatic sciences
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    • v.15 no.2
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    • pp.137-143
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    • 2012
  • The abalone Haliotis discus hannai, is one of the economically important species in the fisheries industry. Abalone intestines are one of the by-products of its processing. To investigate its bioactive potential, abalone intestine was digested using an in vitro gastrointestinal (GI) digestion system containing pepsin, trypsin, and ${\alpha}$-chymotrypsin. The abalone intestine G1 digests (AIGIDs) produced by the GI digestion system were fractionated into AIGID I (> 100 kDa), AIGID II (10-100 kDa), and AIGID III (1-10 kDa) using an ultrafiltration membrane system. Of the three digests, AIGID II and AIGID III exhibited inhibitory effects against matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) in HT1080 human fibrosarcoma cells. Both fractions potently inhibited gelatine digestion by MMP-2 and MMP-9 treated with phorbol 12-myristate 13-acetate (PMA) and migration of HT1080 cells in dose dependently. Furthermore, AIGID II and III attenuated expression of p65, a component of nuclear transcription factor kappa B. These results indicate that of the abalone intestine digests inhibit MMP-2 and MMP-9. Thus, the AIGIDs or their active components may have preventive and therapeutic potential for diseases associated with MMP-2 and MMP-9 activation in fibrosarcoma cells.

Identification of the active components inhibiting the expression of matrix metallopeptidase-9 by TNFα in ethyl acetate extract of Euphorbia humifusa Willd

  • Ahn, Seunghyun;Jung, Hyeryoung;Jung, Yearam;Lee, Junho;Shin, Soon Young;Lim, Yoongho;Lee, Young Han
    • Journal of Applied Biological Chemistry
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    • v.62 no.4
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    • pp.367-374
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    • 2019
  • Euphorbia humifusa Willd (EuH), called Ttang-Bin-Dae in Korea, is a traditional medicinal plant widely used for its anti-inflammatory and antiviral activity. Ethyl acetate (EA) extracts of EuH (EA/EuH) inhibit invasion and metastasis by inhibiting tumor necrosis factor TNFá-induced matrix metalloproteinases (MMP)-9 expression in human breast cancer cells. However, the bioactive components of EA/EuH mediating the inhibition of MMP-9 expression have not been identified. In the present study, three bioactive constituents of EA/EuH were isolated using high-performance liquid chromatography. Nuclear magnetic resonance spectroscopy revealed isoquercetin, avicularin, and astragalin as the bioactive compounds responsible for preventing TNFα-induced MMP-9 mRNA expression in breast cancer cells. These findings suggest that isoquercetin, avicularin, and astragalin could be used as valuable anti-metastatic agents against metastatic cancers.