• Title/Summary/Keyword: MMPS

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The Expression of MMPs and TIMPs in IPF and NSIP (IPF와 NSIP에서 MMPs와 TIMPs의 발현)

  • Kim, Yu Jin;Kim, Jung Ho;Jeon, Hyo Keun;Kim, Mi Kyeong;Jo, Young Chan;Kyung, Sun Yong;An, Chang Hyeok;Lee, Sang Pyo;Park, Jung Woong;Ha, Seung Yeon;Jeong, Sung Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.5
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    • pp.447-455
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    • 2006
  • Background: MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects. Method: The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2, -9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay. Results: (1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue. Conclusions: These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be important factors in the irreversible fibrosis of the lung parenchyme.

Inhibition of the Interleukin-11-STAT3 Axis Attenuates Hypoxia-Induced Migration and Invasion in MDA-MB-231 Breast Cancer Cells

  • Lim, Ji-Hong
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.5
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    • pp.391-396
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    • 2014
  • Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

Cobalt Chloride-Induced Downregulation of Puromycin-Sensitive Aminopeptidase Suppresses the Migration and Invasion of PC-3 Cells

  • Lee, Suk-Hee;Kim, Hwan-Gyu
    • Journal of Microbiology and Biotechnology
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    • v.19 no.5
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    • pp.530-536
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    • 2009
  • Cobalt chloride ($CoCl_2$) treatment of cells in vitro has been shown to induce cellular changes that are similar to those seen following hypoxia. To identify genes that are differentially expressed in response to treatment with $CoCl_2$, we compared the mRNA expression profiles of PC-3 cells that were treated with $CoCl_2$ with those of untreated PC-3 cells, using specific arbitrary primers and two anchored oligo(dT) primers provided in the ACP-based GeneFishing kits. The results of this study demonstrated that the puromycin-sensitive aminopeptidase (PSA) gene was down regulated in PC-3 cells that were treated with $CoCl_2$. This downregulation of PSA expression, in turn, suppressed the proliferation, migration, and invasion of PC-3 cells, as well as the secretion and expression of matrix metalloproteinase-9 (MMP-9).

Metastasis-associated Factors Facilitating the Progression of Colorectal Cancer

  • Zhang, Yao-Yao;Chen, Bin;Ding, Yan-Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2437-2444
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    • 2012
  • Tumor metastasis remains the principal cause of treatment failure and poor prognosis in patients with colorectal cancer. It is a multistage process which includes proteolysis, motility and migration of cells, proliferation in a new site, and neoangiogenesis. A crucial step in the process of intra- and extra-vasation is the activation of proteolytic enzymes capable of degrading the extracellular matrix (ECM). In this stage, urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs) are necessary. Micrometastases need the presence of growth factor and vascular growth factor so that they can form macrometastasis. In addition, cell adhesion molecules (CAMs) and guanine nucleotide exchange factors (GEFs) play important roles in the progression of colorectal cancer and metastatic migration. Further elucidation of the mechanisms of how these molecules contribute will aid in the identification of diagnostic and prognostic markers as well as therapeutic targets for patients with colorectal metastasis.

Sildenafil Citrate Induces Migration of Mouse Aortic Endothelial Cells and Proteinase Secretion

  • Kim, Young-Il;Oh, In-Suk;Park, Seung-Moon;Kim, Hwan-Gyu
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.5
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    • pp.402-407
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    • 2006
  • Vascular endothelial cells release proteinases that degrade the extracellular matrix (ECM), thus enabling cell migration during angiogenesis and vasculogenesis. Sildenafil citrate stimulates the nitric oxide-cyclic guanosine monophosphate pathway through inhibition of phosphodiesterase type V (PDE5). In this report, we examined the mechanisms underlying sildenafil citrate-induced cell migration using cultured mouse aortic endothelial cells (MAECs). Sildenafil citrate induced migration and proteinase secretion by murine endothelial cells. Sildenafil citrate induced the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9, which is inhibited by $NF-{\kappa}B$ inhibitors. Sildenafil citrate also induced the secretion of plasmin, which is inhibited by PI 3'-kinase inhibitors. It is suggested that sildenafil citrate-induced migrating activity in endothelial cells may be accomplished by increased secretion of proteinases.

Plasmin Inhibitory Activity of Medicinal Plants (수종 식물의 Plasmin 저해 활성 검색)

  • Park, Mi-Hyoun;Jung, Hyun-Ju;Bae, Ki-Hwan;Kim, Young-Ho
    • Korean Journal of Pharmacognosy
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    • v.29 no.3
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    • pp.149-154
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    • 1998
  • Binding of urokinase-type plasminogen activator to its cellular receptor accelerate production of plasmin from plasminogen on the cell surface. Plasmin can digest extracellular matrix components and basement membranes through activating certain proMMPs, which is related to the invasiveness to the cells. Plasmin also acts the regulation of blood coagulation and relates closely to cardiovascular diseases such as stroke and coronary occlusion. Therefore, its inhibitors may be useful as antimetastatic agents and to the treatment of cardiovascular diseases. To search for plasmin inhibitors from plant resources, we screened plasmin inhibitory activities with 76 methanol extract of plant species. Among them, three plant samples showed strong inhibitory activities (>70%) and thirteen plant samples showed more than 50% inhibitory activities of plasmin. Their inhibitory activities were not directly related with uPA inhibitory activites and cell viability.

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Inhibitory Effect of Ligularia Stenocephala on the Cancer Metastasis

  • Lee, Dong-Keon;Kim, Jin-Kyu;Kim, Jong-Soo;Park, Kyoung-Jae;Cha, Dong-Seok;Jeon, Hoon
    • Natural Product Sciences
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    • v.18 no.2
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    • pp.89-96
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    • 2012
  • Ligularia stenocephala has been used as a traditional medicine for the treatment of asthma, arthritis, jaundice, and hyperpiesia. In this study, we investigated the anti-metastatic and hypnotic effects of the methanolic extract of L. stenocephala (MLS). Gelatin zymographic analysis revealed that MLS suppresses matrix metalloproteinase-2 (MMP-2) and MMP-9 activities in B16F10 cells. The gene expressions of MMPs were also down-regulated by MLS treatment in a dose-dependent manner. In addition, cancer cell invasion and migration were attenuated by MLS via suppression of NF-${\kappa}B$ activation. The in vivo lung metastasis of B16F10 melanoma cells was also inhibited by the treatment of MLS. These findings show that MLS has anti-metastatic properties, and, therefore, it might be applicable as a valuable anti-metastatic agent.

Effect of Initial Track Tension on the Tractive Performance of Tracked Vehicles (궤도의 초기 장력이 궤도 차량의 견인 성능에 미치는 영향)

  • 김채주;김경욱
    • Transactions of the Korean Society of Automotive Engineers
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    • v.5 no.2
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    • pp.1-12
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    • 1997
  • A computer program was developed to simulate effect of the initial track tension on the tractive performance of tracked vehicles. The performance was evaluated in terms of drawbar pull, motion resistance, tractive coefficient and tractive efficiency. Results of the simulation showed that increase in track tension decreases the sinkage and mean maximum pressure in clay, making the ground pressure distribution more uniform. This tendency became more evident when the number of roadwheels increased. However, such change in MMPs was negligible in firm soils. Motion resistance was also decreased with increase in track tension and the number of roadwheels. Under weak soil conditions, tractive coefficient and efficiency increased generally as the track tension increased for a slip range of 10∼30%. For slippage less than 3∼4%, however, the tractive coefficient decreased with increase in track tension. In general, it was known that increasing track tension improves tractive performance in weak soil conditions. However, high track tension can reduce efficiency due to the increment of internal motion resistance caused by increased track tension.

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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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