• Title/Summary/Keyword: TIMPs

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

  • Ahn, Seong-Min;Sohn, Yeo-Won;Kim, Yun-Soo;Moon , A-Ree
    • Proceedings of the PSK Conference
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    • 2002.10a
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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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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.

Effect of Hepatocyte Growth Factor on the Migration of Human Umbilical Vein Endothelial Cells (혈관내피세포의 이동에 미치는 Hepatocyte Growth Factor의 영향)

  • 오인숙;소상섭;김환규
    • KSBB Journal
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    • v.18 no.6
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    • pp.485-489
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    • 2003
  • Hepatocyte growth factor (HGF) is a mesenchymal-derived cytokine. It exerts a motogenic effect on various target cells, which is displayed either by cell scattering, locomotion, and migration during the wound repair process of cultured cells, or invasiveness through the extracellular matrix, in vitro. Although it is known that HGF influences the motogenic effect of endothelial cells, the precise effects of HGF during migration are still poorly understood. To elucidate the role of HGF in endothelial cell migration, the effect of HGF on endothelial cell migration and MMPs and plasmin production were studied. We found that HGF induces the migration of cultured endothelial cells through increased MMPs and plasmin secretion.

Matrix metalloproteinases and Tissue inhibitors of matrix metalloproteinases in gingival crevicular fluids of periodontitis patients (치주염 환자의 치은열구액에서 MMPs와 TIMPs의 양의 변화)

  • Lee, Sun-Yun;Jung, Yeoun-Ho;Kim, Kyoung-Hwa;Yang, Byung-Keun;Han, Soo-Boo;Chung, Chong-Pyoung;Kim, Tae-Il;Ku, Young;Lee, Yong-Moo;Ko, Jae-Seung;Rhyu, In-Chul
    • Journal of Periodontal and Implant Science
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    • v.34 no.1
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    • pp.139-148
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    • 2004
  • MMPs(Matrix metalloproteinases)는 치주질환에서 주된 조직파괴단백분해효소인 것은 알려져 있고 TIMPs(Tissue inhibitor of Matrix metalloproteinase)는 MMPs의 작용을 억제한다라고 알려져 있다. 이 둘간의 불균형으로 인해서 조직파괴가 더 가속화될 수 있다. 이 두 연구의 목적은 ELISA kit를 사용하여 특정 MMPs(1,2,3,8,9,13)과 TIMPs(1,2)의 양이 건강한 환자와 비교하여서 치주염 환자에서 달라지는지 알아보고 MMPs(1,2,3,8,9,13), TIMPs(1,2)와 치은열구깊이와 GI score와의 관계를 알아보기로 한다. 8명의 만성 치주염 환자와 4명의 급속진행형 치주염 환자가 실험군으로 참여하였고 5명의 건강한 치주조직을 환자가 대조군으로 참여하였다. 임상적인 측정은 GI score와 치주낭측정을 통하여 이루어졌다. 8명의 만성 치주염을 가진 환자와 4명의 급속진행형 치주염을 가진 환자에서 각각 치주낭 깊이가 3mm이하인 부위에서 6개의 치은열구액 표본과 치주낭 깊이가 6mm 이상인 곳에서 6개의 치은열구액 표본을 채취하였다. 건강한 치주조직을 가진 5명의 환자는 단지 치주낭깊이가 3mm 이하인 건강한 부위에서만 치은열구액 표본을 제공하였다. MMPs(1,2,3,8,9,13)과 MIMPs(1,2)의 측정은 Human Biotrack ELISA kit를 사용하여서 측정하였다. 통계처리는 MMPs, MIMPs의 실험군과 대조군의 차이는 Kruskal-Wallis test를 사용하였고 MMPs, TIMPs와 치주낭 깊이와 GI score의 관계정도는 Pearson's correlation coefficient를 사용하였다. 실험결과 대조군과 비교하여 만성 치주염 환자에서 치주낭 깊이가 6mm 이상인 부위에서 MMP9의 수치가 통계적으로 유의할만하게 높았으며(p=0.04) MIMP2의 수치가 대조군과 비교하여 치주낭 깊이가 3mm 이하인 부위를 가진 만성치주염 환자에서 통계적으로 유의할만하게 높았다(=0.049). MMPs(1,2,3,8,9,13), MIMPs(1,2)의 활동성과 치주낭 깊이의 관계에서 둘간의 통계적으로 유의할만한 관계는 존재하지 않았으나 MMP1(r=0.35)과 MMP2(r=0.31)가 상대적으로 높은 관계를 보였다. 또한 MMPs(1,2,3,8,9,13), MIMPs(1,2)의 활동성과 GI score의 관계에서도 둘간의 통계학적으로 유의할만한 관계는 존재하지 않으나 MMP1(r=0.4), MMP2(r=0.29), MMP9(r=0.26)가 상대적으로 높은 관계를 보였다. 이 실험의 결과로 볼 때 MMP9가 만성치주염 환자의 질환이 있는 부위에서만 염증의 지표가 될 수 있으며 MIMP2가 만성치주염 환자의 염증이 없는 부위에서 높은 농도로 존재하는 것으로 보아서 MIMP2가 MMPs에 대한 억제작용을 하여서 염증의 진행을 방해하는 역할을 한다라고 볼 수 있다.

알로에 성분 Ny932의 혈관생성 촉진작용과 그 작용기전

  • 김규원
    • Proceedings of the Korean Society of Toxicology Conference
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    • 1997.05a
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    • pp.57-60
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    • 1997
  • Aloe의 추출 시료들 중 혈관생성을 촉진하는 물질이 G1M1D1M1 분획에 있음을 chorioallantoic-membrane(CAM) assay, in vitro angiogenesis assay, u-PA, PAI, u-PAR, 및 matrix metalloprotease(MMP)의 유전자 발현조사, gelatin zymogram assay, modified CAM assay를 하여 확인 하였다. 그런 다음 G1M1D1M1 분획을 다시 분리하여 단일 성분인 NY932와 3종의 분획들을(U>3,000, 3,000>U>1,000, U<1,000) 얻었다. 이들 각각에 대한 혈관 생성 촉진 작용을 CAM assay 방법으로 조사한 결과 순수단일 성분인NY932가 혈관 생성 촉진 활성을 가장 높게 나타났다. 즉 NY932의 농도를 100ng, 2, 10, 35, 60 $\mu$g으로 투여하였을 때, 각각 2/18($11\%$), 4/10($49\%$), 16/22($73\%$), 15/17($88\%$), 9/9($100\%$)의 혈관생성 촉진 효과를 보였다. 따라서 순수 단일 성분인 NY932의 혈관 생성 촉진 작용기전을 규명하기 위하여 혈관 생성에 관련된 효소들[matrix metalloprotease(MMP)s, urokinase-plasminogen activator(uPA) 등]과 그 저해제들(TIMPs, PAI)의 유전자 발현을 조사하였으며, wounding migration assay등을 수행하였다.

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RETROVIRUS-MEDIATED DELIVERY OF TIMP-2 SUPPRESSES MMP-2 SECRETION AND INVASION: A GENE THERAPY APPROACH

  • Ahn, Seong-Min;Yeowon Sohn;Kim, Yun-Soo;Aree Moon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.200-200
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    • 2001
  • The matrix metalloproteases (MMPs) play important roles in metastasis and invasion in various cell types. An endogenous inhibitor of MMP, tissue inhibitor of metalloprotease-2 (TIMP-2), has high specificity for MMP-2. An imbalance between MMP-2 and TIMP-2 causes the degradation of the extracellular matrix associated with pathological events including invasion and metastasis. Since TIMPs are secreted molecules, they have the potential to be used for gene therapy of certain tumors. (omitted)

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Effects of MMP-2 activation and FSH or LH Hormone Supplementation on Embryo Development in In Vitro Fertilization of Porcine

  • Kim, Sang Hwan;Yoon, Jong Taek
    • Journal of Embryo Transfer
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    • v.33 no.4
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    • pp.313-319
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    • 2018
  • The purpose of this study was to analyze whether FSH and LH hormone treatment directly or indirectly affect embryo development in embryonic development. To determine this, we compared the development of embryonic cells through the expression pattern of MMPs. As a result, 33.8% of blastocysts were formed in FSH added group, 20.8% in LH added group and 10% in FSH + LH added group. In addition, the activity of MMP-9 was highly detected in the FSH-added group, and the expression of Casp-3 was much lower than that of the other groups. These results suggest that the addition of FSH seems to increase the activity of MMP-9 in embryonic cells, and that LH, on the contrary, may activate MMP-2 activity. In addition, the expression level of MMP-2 in the FSH-added group was high in the Trophoblast cell group and in the LH-added group, the hormone ideal secretion might affect the development of the embryonic cell.

Expressions of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-2 with Changes of Interleukin-6 and Interleukin-18 in Atherosclerotic Lesions of Hypercholesterolemic Rabbits (고콜레스테롤혈증 가토의 죽상경화성 병변에서 Interleukin-6와 Interleukin-18의 변화 및 Matrix Metalloproteinase-9과 Tissue Inhibitor of Metalloproteinase-2의 발현)

  • 권영무;김성숙;장봉현
    • Journal of Chest Surgery
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    • v.35 no.6
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    • pp.407-419
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    • 2002
  • Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method: We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result: Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group: 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion: The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

β3GnT8 Regulates Laryngeal Carcinoma Cell Proliferation Via Targeting MMPs/TIMPs and TGF-β1

  • Hua, Dong;Qin, Fang;Shen, Li;Jiang, Zhi;Zou, Shi-Tao;Xu, Lan;Cheng, Zhi-Hong;Wu, Shi-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2087-2093
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    • 2012
  • Previous evidence showed ${\beta}1$, 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of ${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in ${\beta}3GnT8$. Here we showed that cell proliferation was increased in ${\beta}3GnT8$ overexpressed cells but decreased in ${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in ${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of ${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$), whereas ${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of ${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the ${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma.

Effect of N-Acetylcysteine on the Matrix Metalloproteinases and Their Inhibitors in Carbon Tetrachloride-Induced Hepatotoxicity

  • N, Kamalakkannan;Al-Numair, Khalid S.;Al-Assaf, Abdullah H.;Al-Shatwi, Ali A.;Vp, Menon
    • Preventive Nutrition and Food Science
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    • v.14 no.1
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    • pp.14-20
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    • 2009
  • Matrix metalloproteinases (MMPs) are a group of zinc proteases that serve the function of breaking down extracellular matrix (ECM). The present study evaluated the role of N-acetylcysteine (NAC) on the increased deposition of ECM in hepatic and glomerular fibrosis caused by carbon tetrachloride ($CCl_4$). The activity of MMPs increased and the levels of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) decreased in the liver and kidney of $CCl_4$-treated rats. Rats treated with $CCl_4$ and NAC showed increased activities of MMPs and decreased levels of TIMP-1 and TIMP-2 in the liver and kidney. Treatment with NAC resulted in the effective degradation of ECM due to an increase in the activities of MMPs and a decrease in the levels of TIMPs.