• 제목/요약/키워드: Matrix Metalloproteinase-2

검색결과 569건 처리시간 0.029초

Essential Role for c-jun N-terminal Kinase on tPA-induced Matrix Metalloproteinase-9 Regulation in Rat Astrocytes

  • Lee, Sun-Ryung
    • Animal cells and systems
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    • 제10권2호
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    • pp.79-83
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    • 2006
  • Tissue plasminogen activator (tPA) is used to lyse clots and reperfuse brain in ischemic stroke. However, sideeffects of intracerebral hemorrhage (ICH) and edema limit their clinical application. In part, these phenomena has been linked with elevations in matrix metalloproteinase-9 (MMP-9) in neurovascular unit. However little is known about their regulatory signaling pathways in brain cells. Here, I examine the role of MAP kinase pathways in tPA-induced MMP-9 regulation in rat cortical astrocytes. tPA $(1-10\;{\mu}g/ml)$ induced dose-dependent elevations in MMP-9 and MMP-2 in conditioned media. Although tPA increased phosphorylation in two MAP kinases (ERK, JNK), only inhibition of the JNK pathway by the JNK inhibitor SP600126 significantly reduced MMP-9 upregulation. Neither ERK inhibition with U0126 nor p38 inhibition with SB203580 had any significant effects. Taken together, these results suggest that c-jun N-terminal kinase (JNK) plays an essential role for tPA-induced MMP-9 upregulation.

B16-F10 Murine Melanoma 세포의 암전이 억제에 미치는 Diallyl Disulfide의 효과 (The Effects of Diallyl Disulfide on Antimetastatic Potential of B16-F10 Murine Melanoma Cells)

  • 강미경;전혜승;염영나;황명실;박미선;김옥희
    • Toxicological Research
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    • 제22권4호
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    • pp.349-356
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    • 2006
  • Diallyl disulfide (DADS), an oil-soluble organosulfur compound in garlic has been reported to suppress tumor growth and to induce apoptosis in cancer. In the present study, we investigated the effects of DADS on pulmonary metastasis of B16-F10 murine melanoma cells. DADS (i.p. 40 mg/kg) significantly (p<0.05) reduced the number of pulmonary metastatic nodules (48%) in experimental pulmonary metastasis assay. We also found that DADS inhibited adhesion, invasion and migration of B16-F10 melanoma cells in a dose-dependent manner. To study the antimetastatic potential of DADS, we performed the effects of DADS on matrix metalloproteinase activity. DADS significantly inhibited the expression of matrix metalloproteinase-2 activity in B16-F10 cells by gelatin zymography. These results suggest that DADS prevent metastasis in part through suppression of migration of B16-F10 melanoma cells by Inhibiting matrix metalloproteirase-2 responsible for degradation of extracellar matrix.

TIMP-2 Overexpression Suppresses Migraion, Invasiveness and Angiogenesis

  • Ahn, Seong-Min;Yeowon Sohn;Kim, Yun-Soo;Aree Moon
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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    • pp.139-139
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    • 2002
  • An imbalance between matrix metalloproteinase (MMP)-2 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP)-2 causes the degradation of the extracellular matrix associated with pathological events including invasion, metastasis and angiogenesis.(omitted)

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Baicalein Attenuates Oxidative Stress-Induced Expression of Matrix Metalloproteinase-1 by Regulating the ERK/JNK/AP-1 Pathway in Human Keratinocytes

  • Kim, Ki-Cheon;Kang, Sam-Sik;Lee, Jong-Sung;Park, Deok-Hoon;Hyun, Jin-Won
    • Biomolecules & Therapeutics
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    • 제20권1호
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    • pp.57-61
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    • 2012
  • The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [$H_2O_2$]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyfl avone) was investigated for its in vitro activity against $H_2O_2$-induced damage using a human skin keratinocyte model. Baicalein pretreatment signifi cantly inhibited $H_2O_2$-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway.

상아질 접착에 대한 matrix metalloproteinase (MMP)의 영향과 이를 극복하기 위한 전략 (Effects of matrix metallproteinases on dentin bonding and strategies to increase durability of dentin adhesion)

  • 이정현;장주혜;손호현
    • Restorative Dentistry and Endodontics
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    • 제37권1호
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    • pp.2-8
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    • 2012
  • The limited durability of resin-dentin bonds severely compromises the longevity of composite resin restorations. Resin-dentin bond degradation might occur via degradation of water-rich and resin sparse collagen matrices by host-derived matrix metalloproteinases (MMPs). This review article provides overview of current knowledge of the role of MMPs in dentin matrix degradation and four experimental strategies for extending the longevity of resin-dentin bonds. They include: (1) the use of broadspectrum inhibitors of MMPs, (2) the use of cross-linking agents for silencing the activities of MMPs, (3) ethanol wet-bonding with hydrophobic resin, (4) biomimetic remineralization of water-filled collagen matrix. A combination of these strategies will be able to overcome the limitations in resin-dentin adhesion.

CCD-986sk 세포 내 참깨 에탄올 추출물의 항주름 활성 연구 (A Study on the Anti-wrinkle Activities of Sesamum indicum L. Ethanol Extracts on CCD-986sk)

  • 주다혜;유단희;이진영
    • 대한화장품학회지
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    • 제42권4호
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    • pp.377-385
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    • 2016
  • 본 연구에서는 참깨 추출물의 주름개선 화장품 원료로의 가능성을 확인하기 위하여, 참깨의 70% 에탄올 추출물을 제조하여, 엘라스타제 저해능, 콜라게나제 저해능, matrixmetallopoteinases (MMPs)의 단백질, mRNA 발현 저해 효능을 측정하였다. Elastase와 collagenase 저해활성은 $1000{\mu}g/mL$ 농도에서 각각 37.8%와 45%의 효소 활성을 억제를 나타내었다. 섬유아세포에서 참깨 에탄올 추출물의 세포 생존율을 확인한 결과 $100{\mu}g/mL$ 농도에서 96%의 생존율을 보였다. 참깨 에탄올 추출물을 처리한 섬유아세포에서 matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3 (MMP-3)의 단백질 발현 및 mRNA 발현 억제 효과를 확인한 결과 단백질 발현은 $100{\mu}g/mL$ 농도에서 63%, 43%, 49%의 저해율을 나타내었고, mRNA 발현 억제는 최고농도인 $100{\mu}g/mL$에서 각각 82% 79%, 82%의 저해율을 나타내었다. 이러한 결과로 보아 참깨 70% 에탄올 추출물이 주름개선용 기능성 화장품 소재로서의 응용이 가능할 것으로 판단되었다.

LIGHT is Expressed in Foam Cells and Involved in Destabilization of Atherosclerotic Plaques through Induction of Matrix Metalloproteinase-9 and IL-8

  • Kim, Won-Jung;Lee, Won-Ha
    • IMMUNE NETWORK
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    • 제4권2호
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    • pp.116-122
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    • 2004
  • Background: LIGHT (TNFSF14) is a member of tumor necrosis factor superfamily and is the ligand for TR2 (TNFRSF14/HVEM). LIGHT is known to have proinflammatory roles in atherosclerosis. Methods: To find out the expression pattern of LIGHT in atherosclerotic plaques, immunohistochemical analysis was performed on human carotid atherosclerotic plaque specimens. LIGHT induced atherogenic events using human monocytic cell line THP-1 were also investigated. Results: Immunohistochemical analysis revealed expression of LIGHT and TR2 in foam cell rich regions in the atherosclerotic plaques. Double immunohistochemical analysis further confirmed the expression of LIGHT in foam cells. Stimulation of THP-1 cells, which express TR2, with either recombinant LIGHT or immobilized anti-TR2 monoclonal antibody induced interleukin-8 and matrix metalloproteinase(MMP)-9. Electrophoretic mobility shift assay demonstrated that LIGHT induces nuclear localization of transcription factor, nuclear factor $(NF)-{\kappa}B$. LIGHT induced activation of MMP-9 is mediated by $NF-{\kappa}B$, since treatment of THP-1 cells with the $NF-{\kappa}B$ inhibitor PDTC (pyrrolidine dithiocarbamate) completely blocked the activation of MMP-9. Conclusion: These data indicate that LIGHT is expressed in foam cells in atherosclerotic plaques and is involved in atherogenesis through activation of pro-atherogenic cytokine IL-8 and destabilization of plaque by inducing matrix degrading enzyme.

Caveolin-1 inhibits membrane-type 1 matrix metalloproteinase activity

  • Kim, Hye-Nan;Chung, Hye-Shin
    • BMB Reports
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    • 제41권12호
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    • pp.858-862
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    • 2008
  • Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent proteinase found in cholesterol-rich lipid rafts on the plasma membrane. MT1-MMP hydrolyzes extracellular matrix (ECM) proteins, activates pro-matrix metalloproteinase-2 (proMMP-2) and plays an important role in ECM remodeling, cancer cell migration and metastasis. The role of caveolin-1, an integral protein of caveolae, in the activation of MT1-MMP remains largely unknown. Here, we show that the expression of caveolin-1 attenuates the activation of proMMP-2, reduces proteolytic cleavage of ECM and inhibits cell migration. We utilized the cytoplasmic tail domain deletion (${\Delta}CT$) or the E240A mutant of MT1-MMP. Co-expression of caveolin-1 with the wild-type or the ${\Delta}CT$ MT1-MMP decreased the proMMP-2 activation and inhibited collagen degradation and cell migration. Caveolin-1 had no effect on the catalytically inert E240A MT1-MMP. Our findings suggest that caveolin-1 is essential in the down-regulation of MT1-MMP activity by promoting internalization from the cell surface.

Retrovirus-mediated Delivery of TIMP-2 Inhibits Migration. Invasion and Angiogenesis

  • Ahn, Seong-Min;Sohn, Yeo-Won;Kim, Yun-Soo;Moon , A-Ree
    • 대한약학회:학술대회논문집
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    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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    • pp.325.3-326
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    • 2002
  • An imbalance between matrix metalloproteinase (MMP)-2 and its endogenous inhibitor. tissue inhibitor of metalloproteinase (TIMP)-2 causes the degradation of the extracellular matrix associated with pathological events including invasion. metastasis and angiogenesis. Since TIMPs are secreted molecules. they have the potential to be used for gene therapy of certain tumors. (omitted)

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갑상선 유두상미세암종에서 갑상선외 침윤, 다원성 및 경부전이에 대한 Matrix Metalloproteinase 2 및 Tissue Inhibitor of Matrix Metalloproteinase 2 발현의 의의 : 부정적 결과 보고 (Expression of Matrix Metalloproteinase 2 and Tissue Inhibitor of Metalloproteinase 2 in Papillary Microcarcinoma of the Thyroid Gland are Not Related with Extrathyroid Invasion, Multifocality and Lymph Node Metastasis of the Tumor)

  • 최승호;남순열;조경자;김상윤
    • 대한두경부종양학회지
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    • 제21권2호
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    • pp.121-125
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    • 2005
  • Objectives: To investigate the role of MMP-2 and TIMP-2 in the invasion and metastasis of thyroid papillary microcarcinomas. Materials and Methods: We performed immunohistochemical study on MMP-2 and its tissue inhibitor (TIMP-2) using tissue microarrays containing 2 cores of 40 microPTC and 8 non-neoplastic thyroid tissue. The expression intensity was semiquantitatively scored as -, ${\pm}$, +1, +2, and +3. Results: Both MMP-2 and TIMP-2 expression was observed in all tumors(100%) and in 1 of 8 non-neoplastic tissue(12.5%), and the positive staining was restricted to the epithelial cells. In 17 and 23 tumors with or without extrathyroid invasion, respectively, 8(47%) and 10(43%) cases showed moderate to strong(+23) positivity for MMP-2. TIMP-2 expression was moderate to strong in 13 cases(76%) and 16 cases(70%) in each group. In multifocal and solitary tumors, 3 of 6(50%) and 11 of 21(52%) cases showed moderate to strong MMP-2 expression, and 5/6(83%) and 15/21(71%) showed moderate to strong TIMP-2 expression. Conclusion: There is no relationship between MMP-2 or TIMP-2 expression and extrathyroid invasion or tumor multifocality in papillary microcarcinoma of the thyroid gland.