• Title/Summary/Keyword: MMP-3

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Effect of Tetracycline Analogues on The Activity of Matrix Metalloproteinase-3 in Gingival Fibroblasts (테트라사이클린계 약물이 치은섬유아세포내 MMP-3의 활성도에 미치는 영향)

  • Cho, Jong-Hee;Kim, Sang-Mok;Kim, Byung-Ock;Han, Kyung-Yoon
    • Journal of Periodontal and Implant Science
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    • v.29 no.3
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    • pp.677-693
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    • 1999
  • Extracellular matrix component is degraded by enzymes of thematrix metalloproteinases(MMPs). MMPs are produced by both hemopoietic and structural cells. Increased activity of MMP-3 in periodontium is strongly associated with inflammatory periodontal disease. The purpose of the present study was to determine the effect of tetracycline analogues on the activity of MMP-3. Tetracycline-HCl, doxycycline-HCl, and minocycline-HCl were applied to huamn gingival fibroblasts at various concentrations of 10, 25, 50, 100, 200${\mu}g$/ml, and 1 hour later IL-$1{\beta}$ of 25ng/ml was added. After incubation for 24 hours the cells were reacted by enzyme-linked immunosorbent assay using proMMP-3 ELISA kit. The optical density was measured by microwell plate reader at 450nm. The relative activity of MMP-3 was calculated as the percentage of the optical density of each experimental group to that of the control. The difference of the optical density and the relative activity of MMP-3 between the experimental groups and the control wasstatistically analyzed by one way ANOVA. The results were as follows: 1. Tetracycline-HCl showed the tendency to inhibit the activity of MMP-3 at the concentration lower than 25${\mu}g$/ml, but increased significantly the activity of MMP-3 at the concentration of 200${\mu}g$/ml(p<0.05). 2. Doxycycline-HCl inhibited significantly the activity of MMP-3 at the concentration lower than 100${\mu}g$/ml, but increased significantly the activity of MMP-3 at the concentration of 200${\mu}g$/ml(p<0.05). 3. Minocycline-HCl inhibited the activity of MMP-3 at the concentration in the range of 10 to 200${\mu}g$/ml. Within the limit of the present study, the above results suggested that the low concentration of tetracycline analogues could inhibit the activity of MMP-3 induced by IL-$1{\beta}$ in human gingival fibroblasts.

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The Expression of Matrix Metalloproteinases Activated Differently on In-Vitro Maturation of oocytes Cytoplasm and Cumulus Cells in Bovine (소 난자의 체외성숙시 난구세포와 난세포질에서 다르게 발현되는 Matrix Metalloproteinases의 분석)

  • Kim, Sang-Hwan;Yoon, Jong-Taek
    • Journal of Embryo Transfer
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    • v.33 no.3
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    • pp.99-105
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    • 2018
  • To determine the differences in the in-vitro ovum maturation process of bovine, we compared the expression of MMPs in these oocytes and cumulus cell throughout oocytes maturated. In an attempt to investigate the effect of MMP activation and inhibitors in total protein of cumulus cell and, oocytes during oocytes maturation, we examined and monitored the localization and expression of MMPs (MMP-2 and MMP-9), TIMPs (TIMP-2 and TIMP-3), as well as their expression profiles (Real-time PCR, Gelatin Zymography and ELISA). Our results that the bovine oocytes MMP-2 and MMP-9 level was significantly associated with the rate of maturity of oocytes (P<0.05). In cumulus cell, MMP-2 was highly expressed in all stages of the oocyte's maturation. The final oocytes maturation exhibited strong gelatinase activity. There was no significant correlation between cumulus cell MMP-9 and the maturation rate of oocytes. However, for the oocyte cytoplasm MMP-9 expression was significant correlation to the maturation oocytes. There was no significant correlation between cumulonimbus cells MMP-9 and oocyte maturation rates; however, for oocyte cytoplasm, MMP-9 expression was significantly correlated with mature oocyte. However, the TIMP-1 and TIMP-2 protein expression patterns are not correlated with the maturation rate of the oocyte. Our results suggest that MMP different expression pattern may regulate the morphological remodeling of oocyte's in the cumulus cell. Further, the MMP-2 expression has a strong relation with a higher maturation rate of the oocyte.

Influence of Menstrual Cycle on Inflammatory Markers in Gingival Crevicular Fluid : Pilot Study (월경주기에 따른 치은열구액 내 염증지표의 변화: 예비 연구)

  • Park, Hoo-Seob;Hwang, Soo-Jeong;Cho, Min-Jeong;Kim, Do-Kyoung;Yang, Seon-Youn
    • Journal of dental hygiene science
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    • v.12 no.1
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    • pp.71-77
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    • 2012
  • Sex Hormones exert significant influence in body physiology throughout life. Some reports suggested increased sex hormone levels correlate with an increased prevalence of gingivitis. The objectives of this pilot study are to(1) address the link between menstrual cycle and MMP-9, MMP-8, IL-$1{\beta}$ of gingival crevicular fluid during 4 weeks and (2) discuss the major biomarker of periodontal status. 7 female and 3 male volunteer who didn't have smoking habit, medical and dental disease after informed consent, were seen twice a week for 4 weeks. GCF samples were collected and GCF levels of MMP-9, MMP-8, IL-$1{\beta}$ were measured by enzyme-linked immunosorbent assay. The GCF levels of MMP-9, MMP-8, IL-$1{\beta}$ had fluctuation according to menstrual cycle, but the changes of those were not significant by Friedman matched samples test. There is no difference between female and male subjects by Mann-Whitney U test. The correlation of MMP-8, MMP-9 and IL-$1{\beta}$ showed strong by Spearman correlation(0.644-0.945). This study confirms menstrual cycle doesn't influence the periodontium of healthy female subjects.

Effect of Green Tea Catechins on the Expression and Activity of MMPs and Type I Procollagen Synthesis in Human Dermal Fibroblasts (사람 섬유아세포에서 녹차 카테킨이 노화 인자인 MMP와 type 1 Procollagen 발현에 미치는 영향)

  • Shin, Hyun-Jung;Kim, Su-Nam;Kim, Jung-Ki;Lee, Byeong-Gon;Chang, Ih-Seoup
    • 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.

MAP Kinase Activation is Required for the MMP-9 Induction by TNF-Stimulation

  • Kim, Kyung-Chan;Lee, Chu-Hee
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1257-1262
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    • 2005
  • MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-$\alpha$ stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-$\alpha$ stimulation. To investigate the signaling pathway underlined in TNF-$\alpha$ induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-$\alpha$ treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-$\alpha$. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-$\alpha$ induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-$\alpha$. Taken together, we found that TNF-$\alpha$ stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.

Viscum album and its Constituents Downregulate MMP-13 Expression in Chondrocytes and Protect Cartilage Degradation

  • Lee, Ju Hee;Kwon, Yong Soo;Jung, Da Young;Kim, Na Young;Lim, Hyun;Kim, Hyun Pyo
    • Natural Product Sciences
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    • v.27 no.3
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    • pp.151-160
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    • 2021
  • Under some pathological conditions such as osteoarthritis, matrix metalloproteinases (MMPs) including MMP-13 have an important role in degrading cartilage materials. When the regulatory effects of some herbal extracts on MMP-13 expression were examined to evaluate the cartilage-protective potential, the ethanol extract of the radix of Viscum album was found to strongly downregulate MMP-13 induction in IL-1β-treated chondrocytes, SW1353 cells. Based on this finding, activity-guided separation was carried out, which yielded five constituents identified as 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (1), hesperetin-7-glucoside (2), syringin (3), homoflavoyadorinin B (4), and 4,4'-dihydroxy-3,6'-dimethoxychalcone-2'-glucoside (5). Of these, 1 and 5 significantly inhibited MMP-13 expression in SW1353 cells, with 5 being the most potent. Compound 5, a chalcone derivative, showed the downregulation of MMP-13 at 20 - 100 μM. The mechanism study revealed that 5 exerted MMP-13 down-regulatory action, at least in part, by interrupting the signal transducer and activator of transcription 1 (STAT1) activation pathway. Furthermore, this compound protected against cartilage degradation in an IL-1-treated rabbit cartilage explant culture. All these findings demonstrated for the first time that Viscum album and its constituents, especially chalcone derivative (5), possessed cartilage-protective activity. These natural products may have the potential for alleviating cartilage degradation.

Anti-Metastatic Activity of Juniperus chinensis Extract by Galectin-3 Inhibition (향나무 추출물의 Galectin-3 저해에 의한 암 전이 억제 효과)

  • Lee, Keyong Ho;Rhee, Ki-Hyeong
    • The Korean Journal of Food And Nutrition
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    • v.25 no.4
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    • pp.713-718
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    • 2012
  • The purpose of this study was to examine the anti-metastatic effect of Juniperus chinensis extract by inhibition of galectin-3 expression. For this study, we carried out the experiment of galectin-3 expression assay and in vivo metastasis mouse model bearing colon 26-M3.1 lung carcinoma, and also MMP-1, MMP-2 and MMP-9 inhibitory assays relating metastasis mechanism. J. chinensis extract significantly showed the inhibitory effect of basal expression and MNNG-induced expression of galectin-3 in colon 26-M3.1 lung carcinoma at the all tested doses (5, 50 and $500{\mu}g/m{\ell}$). In case of the inhibition of MMP-1, MMP-2 and MMP-9, the weak activity was showed at the doses of 50 and $500{\mu}g/m{\ell}$ and was not detected at the dose of $5{\mu}g/m{\ell}$. However, J. chinensis extract significantly showed the anti-metastatic activity on mouse mode bearing colon 26-M3.1 lung carcinoma. Therefore, this study strongly suggests that J. chinensis is a potent inhibitor of galectin-3 expression, and holds great promise for use in inhibiting metastasis induced by elevated expression of galectin-3.

Effect of ganglioside GD3 synthase gene expression on VSMC proliferation via ERK1/2 pathway, cell cycle progression and MMP-9 expression

  • Lee, Young-Choon;Kim, Cheorl-Ho
    • Proceedings of the Korean Society of Plant Biotechnology Conference
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    • 2004.10a
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    • pp.81-90
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    • 2004
  • Sialic acid containing glycosphingolipids (gangliosides) have been implicated in the regulation of various biological phenomena such as atherosclerosis. Recent report suggeststhat exogenously supplied disialoganglioside (GD3) serves a dual role in vascular smooth muscle cells (VSMC) proliferation and apoptosis. However, the role of the GD3 synthase gene in VSMC responses has not yet been elucidated. To determine whether a ganglioside is able to modulate VSMC growth. the effect of overexpression of the GD3 synthase gene on DNA synthesis was examined. The results show that the overexpression of this gene has a potent inhibitory effect on DNA synthesis and ERK phosphorylation in cultured VSMC in the presence of PDGF. The suppression of the GD3 synthase gene was correlated with the down-regulation of cyclinE/CDK2. the up-regulation of the CDK inhibitor p21 and blocking of the p27 inhibition,whereas up-regulation of p53 as the result of GD3 synthase gene expression was not observed. Consistently, blockade of GD3 function with anti-GD3 antibody reversed VSMC proliferation and cell cycle proteins. The expression of the CD3 synthase gene also led to the inhibition of TNF--induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, GD3 synthase gene expression strongly decreased MMP-9 promoteractivlty in response to TNF-. This inhibition was characterized by the down-regulation of MMP-9,which was Iranscriptionally regulated at NF-B and activation protein-1 (AP-1) sites in the MMP-9promoter Finally, the overexpression of MMP-9 in GD3 synthase transfectant cells rescued VSMC proliferation. However MMP-2 overexpression was not affected the cell proliferation. These findings suggest that the fl13 synthase gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis.

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Effects of quercetin on cell differentiation and adipogenesis in 3T3-L1 adipocytes

  • Hong, Seo Young;Ha, Ae Wha;Kim, Wookyoung
    • Nutrition Research and Practice
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    • v.15 no.4
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    • pp.444-455
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    • 2021
  • BACKGROUND/OBJECTIVES: Adipocytes undergo angiogenesis to receive nutrients and oxygen needed for adipocyte' growth and differentiation. No study relating quercetin with angiogenesis in adipocytes exists. Therefore, this study investigated the role of quercetin on adipogenesis in 3T3-L1 cells, acting through matrix metalloproteinases (MMPs). MATERIALS/METHODS: After proliferating preadipocytes into adipocytes, various quercetin concentrations were added to adipocytes, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to evaluate cell proliferation. Glycerol-3-phosphate dehydrogenase (GPDH) activity was investigated as an indicator of fat accumulation. The mRNA expressions of transcription factors related to adipocyte differentiation, CCAAT/enhancer-binding proteins (C/EBPs), peroxisomal proliferatoractivated receptors (PPAR)-γ, and adipocyte protein 2 (aP2), were investigated. The mRNA expressions of proteins related to angiogenesis, vascular endothelial growth factor (VEGF)-α, vascular endothelial growth factor receptor (VEGFR)-2, MMP-2, and MMP-9, were investigated. Enzyme activities and concentrations of MMP-2 and MMP-9 were also measured. RESULTS: Quercetin treatment suppressed fat accumulation and the expressions of adipocyte differentiation-related genes (C/EBPα, C/EBPβ, PPAR-γ, and aP2) in a concentration-dependent manner in 3T3-L1 cells. Quercetin treatments reduced the mRNA expressions of VEGF-α, VEGFR-2, MMP-2, and MMP-9 in 3T3-L1 cells. The activities and concentrations of MMP-2 and MMP-9 were also decreased significantly as the concentration of quercetin increased. CONCLUSIONS: The results confirm that quercetin inhibits adipose tissue differentiation and fat accumulation in 3T3-L1 cells, which could occur through inhibition of the angiogenesis process related to MMPs.

IMMUNOHISTOCHEMICAL STUDY ON EXPRESSION OF MMP-2 AND MMP-9 IN IRRITATION FIBROMA, ORAL LEUKOPLAKIA AND ORAL SQUAMOUS CELL CARCINOMA (자극성 섬유종, 구강백반증 및 구강편평세포암종에서 MMP-2 및 MMP-9 발현에 대한 면역조직화학적 연구)

  • Kim, Moon-Key;Lee, Eun-Ha;Kim, Jin;Lee, Eui-Woong;Cha, In-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.4
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    • pp.352-359
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    • 2006
  • MMP-2 and MMP-9, type IV collagenases which degrade basement membrane, have been known to play important roles in invasion and metastasis of tumor cells, In addition, they seem to be involved in cell differentiation, apoptosis, angiogenesis and immunity, etc. We immunohistochemically examined epithelial and stromal expressions of MMP-2 and MMP-9 in irritation fibroma, oral leukoplakia, and oral squamous cell carcinoma (OSCC) and have some results as follows: 1. Irritation fibromas, oral leukoplakias and OSCCs mostly showed increased expression of MMP-2 and MMP-9 in the epithelium and connective tissue compared with normal mucosa. 2. There was a significant difference in the epithelial expression of MMP-2 and MMP-9 between irritation fibroma and oral leukoplakia. 3. There was a significant difference in the epithelial and stromal expression of MMP-2 and MMP-9 between irritation fibroma and OSCC. 4. There was a significant difference in the stromal expression of MMP-9 between oral leukoplakia and OSCC. We concluded that rritation fibroma, oral leukoplakia and OSCC have somewhat different characteristics of MMP-2 and MMP-9 expressions, which perhaps result from different pathogenesis.