• Title/Summary/Keyword: Matrix Metalloproteinase(MMP)

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MMP-1 promoter polymorphism in Korean with generalized aggressive periodontitis

  • Oh, Hyong-Suk;Kim, Ok-Su;Kim, Young-Jun;Chung, Hyun-Ju
    • Journal of Periodontal and Implant Science
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    • v.39 no.sup2
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    • pp.269-278
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    • 2009
  • Purpose: The aim of this study was to investigate matrix metalloproteinase 1 (MMP-1) gene polymorphism (1G/2G at -1607 and A/G at -519) in Korean subject and to assess the association between polymorphism and periodontal status. Methods: Forty nine generalized aggressive periodontitis (GAP) patients and 57 periodontally healthy children were recruited and genomic DNA was extracted from buccal swab. The polymorphisms of MMP-1 promoter genes were determined by polymerase chain reaction and restriction fragment length product (PCR-RFLP) method. The distribution of genotype and allele frequency was compared between 2 groups by ${\chi}^2$ test. Results: There was a significant difference in the distribution of genotypes and frequency of alleles between the GAP and reference groups at the position - 519 of MMP-1 gene promoter (P<0.05). Allele G carrier rate was significantly lower in GAP group than that of the reference group (P< 0.001). At the position -1607 of MMP-1 gene promoter, genotype distribution and allele frequency showed no statistically significant difference between the groups. However, in the female group, a significant difference was observed between the groups for the genotype distribution, allele frequency and allele 1G carrier rate (P< 0.05). Conclusions: The DNA polymorphism at the MMP-1 gene promoter might be associated with GAP in Korean.

Effect of Deep Sea Water on Cytochrome P450 1A1, Aromatase and MMP-9. (해양심층수의 cytochrome P450 1A1, aromatase 및 MMP-9 활성 억제 효과)

  • Shon, Yun-Hee;Kim, Mee-Kyung;Nam, Kyung-Soo
    • Journal of Life Science
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    • v.18 no.4
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    • pp.503-508
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    • 2008
  • Deep sea water from the East sea was tested for breast cancer chemoprevention and metastasis by measuring the activities of cytochrome P450 1A1 and aromatase, invasiveness, and activity and expression of matrix metalloproteinase (MMP)-9 in breast MDA-MB-231 cancer cell. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P450 1A1 activity. Deep sea water showed 27.1, 45.4 and 51.9% inhibition of microsomal aromatase activity at the hardness of 600, 800 and 1,000, respectively. In addition deep sea water inhibited not only the invasiveness of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MDA-MB-231 cells through matrigel-coated membrane in a hardness-dependent manner but also the activity and expression of MMP-9 in MDA-MB-231 cell.

The Protective Effect of Spirulina-derived Phycocyanin on Dermal Fibroblasts Induced by UV Rays (자외선으로 손상을 유도한 피부섬유아세포에서 스피룰리나 유래 피코시아닌의 보호 효과)

  • Yang, Jae Chan
    • Journal of the Korean Applied Science and Technology
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    • v.38 no.5
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    • pp.1249-1254
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    • 2021
  • UV induce oxidative stress and increase matrix metalloproteinase (MMP) expression, resulting in skin aging. Thus, preventing skin damage from ultraviolet B (UVB)-induced skin damage can attenuate skin aging. Spirulina is comprised of prokaryotes a powerful antioxidant. This study aimed to investigate the photoprotective effects of spirulina-derived phycocyanin (PC) against UVB radiation using human skin fibroblast. As a results, PC showed no toxicity at concentrations of 5-40 ㎍/mL in terms of fibroblast viability. Survival rate of UVB-irradiated fibroblast incresased to 73.5% from 50.5% with PC treatment. UVB treatment increased MMP-1 and MMP-9 expression whereas PC treatment decreased it. The results indicate that PC might reduce or prevent skin aging by reducing UVB irradiation-induced skin wrinkles and free radicals.

Gilgyung-tang Inhibits the Migration and Invasion of Human Bladder Cancer 5637 Cells through the Tightening of Tight Junctions and Inhibition of Matrix Metalloproteinase Activity (길경탕의 치밀결합 강화 및 MMPs의 활성 억제를 통한 인체방광암세포의 이동성 및 침윤성의 억제)

  • Hong, Su-hyun;Choi, Yung-hyun
    • The Journal of Internal Korean Medicine
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    • v.37 no.1
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    • pp.16-25
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    • 2016
  • Objectives: Gilgyung-tang (GGT) has been used as one of the main multi-herb formulas to treat “Peo-ong” (lung abscess). In this study, we investigated the inhibitory effects of water extracts of GGT on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, in human bladder cancer 5637 cells.Methods: Effects on cell viability were quantified using an MTT assay. To analyze the anti-metastatic effects, we conducted a wound healing migration assay, an in vitro invasiveness assay, and a measurement of the transepithelial electrical resistance (TER). The expression of protein and mRNA were measured by Western blotting and real-time polymerase chain reaction (RT-PCR), respectively.Results: GGT markedly inhibited the cell motility and invasiveness of 5637 cells within the concentration range that was not cytotoxic. The inhibitory effects of GGT on cell invasiveness were associated with tightening of the tight junctions (TJs), which was demonstrated by an increase in the TER. The RT-PCR and Western blotting results indicated that GGT decreased the levels of claudin proteins. GGT also inhibited the activity and expression of matrix metalloproteinase (MMP)-2 and -9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase-1 and -2.Conclusions: Our findings suggest that GGT reduces both the migration and the invasion of 5637 cells by modulating the activity of TJs and MMPs.

Comparison of the Effects of Matrix Metalloproteinase Inhibitors on TNF-α Release from Activated Microglia and TNF-α Converting Enzyme Activity

  • Lee, Eun-Jung;Moon, Pyong-Gon;Baek, Moon-Chang;Kim, Hee-Sun
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.414-419
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    • 2014
  • Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate cell-matrix composition and are also involved in processing various bioactive molecules such as cell-surface receptors, chemokines, and cytokines. Our group recently reported that MMP-3, -8, and -9 are upregulated during microglial activation and play a role as proinflammatory mediators (Lee et al., 2010, 2014). In particular, we demonstrated that MMP-8 has tumor necrosis factor alpha (TNF-${\alpha}$)-converting enzyme (TACE) activity by cleaving the prodomain of TNF-${\alpha}$ and that inhibition of MMP-8 inhibits TACE activity. The present study was undertaken to compare the effect of MMP-8 inhibitor (M8I) with those of inhibitors of other MMPs, such as MMP-3 (NNGH) or MMP-9 (M9I), in their regulation of TNF-${\alpha}$ activity. We found that the MMP inhibitors suppressed TNF-${\alpha}$ secretion from lipopolysaccharide (LPS)-stimulated BV2 microglial cells in an order of efficacy: M8I>NNGH>M9I. In addition, MMP inhibitors suppressed the activity of recombinant TACE protein in the same efficacy order as that of TNF-${\alpha}$ inhibition (M8I>NNGH>M9I), proving a direct correlation between TACE activity and TNF-${\alpha}$ secretion. A subsequent pro-TNF-${\alpha}$ cleavage assay revealed that both MMP-3 and MMP-9 cleave a prodomain of TNF-${\alpha}$, suggesting that MMP-3 and MMP-9 also have TACE activity. However, the number and position of cleavage sites varied between MMP-3, -8, and -9. Collectively, the concurrent inhibition of MMP and TACE by NNGH, M8I, or M9I may contribute to their strong anti-inflammatory and neuroprotective effects.

Matrix Metalloproteinase-2 (-1306 C>T) Promoter Polymorphism and Risk of Colorectal Cancer in the Saudi Population

  • Saeed, Hesham Mahmoud;Alanazi, Mohammad Saud;Parine, Narasimha Reddy;Shaik, Jilani;Semlali, Abdelhabib;Alharbi, Othman;Azzam, Nahla;Aljebreen, Abdulrahman;Almadi, Majid;Shalaby, Manal Aly
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6025-6030
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    • 2013
  • Background: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with the T allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associated with susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC patients and 4 different cancer cell lines. Materials and Methods: TaqMan allele discrimination assays and DNA sequencing techniques were used to investigate the $C^{-1306}T$ SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 colon cancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumor margins. Results and Conclusions: The MMP-2 $C^{-1306}T$ SNP in the promoter region was associated with CRC in our Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients. The MMP-2 $C^{-1306}T$ SNP is significantly associated with CRC in the Saudi population and this finding suggested that MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of this gene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.

Protein Expression of Matrix Metalloproteinases of Mouse Reproductive Organs During Estrous Cycle (생식주기에 따른 자성 생쥐의 생식기관의 Matrix Metalloproteinase의 단백질 발현)

  • Kim, Moon-Young;Lee, Ki-Won;Kim, Hae-Kwon;Kim, Moon-Kyoo;Cho, Dong-Jae
    • Clinical and Experimental Reproductive Medicine
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    • v.25 no.2
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    • pp.161-170
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    • 1998
  • Protein expression patterns of matrix metalloproteinases (MMPs) were examined in mouse reproductive organs during estrous cycle. Estrous cycle was classified into diestrus, proestrus, estrus or metestus and MMP expression was analyzed by zymography using gelatin as a substrate. Uterine fluid (UF) obtained both at diestrus and proestrus exhibited 4 major MMPs including 106kDa, 64kDa, 62kDa and 59kDa gelatinases. However, in UF at estrus, the gelatinolytic activity of 64kDa MMP disappeared and that of 106kDa and 62kDa MMPs dramatically decreased. At metestrus, 64kDa MMP activity reappeared and 106kDa and 62kDa MMP exhibited increased activities such that the band intensity of 106kDa was comparable to that in UF at diestrus. Gelatinolytic activity of 59kDa MMP was not changed throughout the cycle. Both ovarian and oviductal tissue homogenate revealed 4 MMPs which corresponded to the 4 MMPs of UF. However, unlike UF MMPs, gelatinolytic activity of these MMPs did not show distinct changes throughout the cycle. Either an inhibitor of MMP, 1,10-phenanthroline, or a metal chelator, EDTA, abolished the appearance of the above MMP activities in gelatinated gel whereas a serine proteinase inhibitor, phcnylmethylsulfonyl fluoride, failed to inhibit the appearance of MMP activities, proving that gelatinolytic activity of the above reproductive tissues were due to the enzymatic activity of MMP. When gclatinolytic activity of mouse serum was examined, it revealed 5 MMPs (131kDa, 106kDa, 89kDa, 64kDa and 62kDa bands) and one gelatinase (84kDa) band. From these results, it is concluded that the protein expression of MMPs of mouse reproductive organs, particularly uterus, is temporally regulated during estrous cycle and uterine 106kDa, 64kDa and 62kDa MMPs are suggested to play an important role in cyclic tissue remodeling of mouse uterus.

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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 EFFECT OF THE GENISTEIN ON THE PROLIFERATION OF HT1080 AND EXPRESSION OF MEMBRANE TYPE 1-MATRIX METALLOPROTEINASE (MT1-MMP) mRNA (Genistein이 사람 섬유육종 세포주 증식 및 Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) mRNA 발현에 미치는 영향)

  • Kang, Jin-Han;Myoung, Hoon;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.4
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    • pp.314-320
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    • 2001
  • Matrix metalloproteinases have long been viewed as ideal candidates for proteinases that enables tumor cells to permeated basement membrane defenses and invade surrounding tissue. There is growing evidence that the MMPs have an expanded role, as they are important for the creation and maintenance of a microenvironment that facilitates growth and angiogenesis of tumors at primary and metastatic sites. MT-MMPs are not secreted but instead remaining attached to cell surfaces. Although not all of the MT-MMPs are fully characterized, MT-MMPs have important role in localizing and activating secreted MMPs. The MMP genes are transcriptionally responsive to a wide variety of oncogene, growth factors, cytokine, and hormones. Currently, a number of MMP inhibitors are being developed and some have reached clinical trials as anti-metastatic or anti-cancer therapies. MT1-MMP is involved in the activation of proMMP-2. MT1-MMP is significant not only as a tumor marker but as a new target for chemotherapy against cancer. The purpose of this study was to evaluate the effects of protein kinase C inhibitor(genistein) on the proliferation of HT1080 and expression of MT1-MMP mRNA. Human fibrosarcoma cell line HT1080 was cultured and divided 2 groups. The experimental group was treated with $100{\mu}M$ genistein and incubated 12h, 24h for $[3^H]-thymidine$ uptake assay and northern hybridization individually. And the control group was treated with same amount of PBS for the above procedures. $[3^H]-thymidine$ incorporation was measured with ${\beta}$ ray detector. And RT-PCR and northern blotting for MT1-MMP mRNA was performed. The results were as follows 1. $[3^H]-thymidine$ uptake was reduced in experimental group with statistical significance. 2. MT1-MMP mRNA expression was significantly reduced in experimental group. These results showed that protein kinase C inhibitor (genistein) inhibited proliferation of HT1080 and almost completely blocked transcription of MT1-MMP mRNA. So, it is possible to use the protein kinase inhibitor (genistein) as anti-metastatic and anti-proliferative agent.

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Anti-Aging Effect of Ligustrum japonicum Extract in the Human Fibroblast Cells (피부 섬유아세포에서 광나무 추출물의 항 노화 효과)

  • Kim, Yun-Jeong;Lee, Yu-Ri;Cheon, Jong-Woo;Lee, Hyun-Sang
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.36 no.4
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    • pp.295-301
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    • 2010
  • To develop wrinkle care cosmetic ingredients, various species of plant extracts were investigated. Accordingly, Ligustrum japonicum was selected as a candidate for developing cosmetic ingredient. By high performance liquid chromatography, 31.06 % of oleanolic acid and 8.92 % of ursolic acid which are well-known for anti-wrinkle effect were analyzed. The possibility of Ligustrum japonicum fruits extract (LJE) as a cosmetic ingredient was investigated using several biomarkers related to anti-aging, including anti-wrinkle, moisturizing and anti-inflammation. Procollagen type I and hyaluronan synthase-3 gene expression were increased by LJE in a concentration-dependent manner, whereas elastase activity and matrix metalloproteinase (MMP)-1, MMP-2 and cyclooxygenase-2 gene expression were inhibited. As the results LJE is applicable for a potential cosmetic ingredient focused on anti-aging effect.