• Title/Summary/Keyword: Matrix metalloproteinase-3

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Involvement of PI3K and MMP1 in PDGF-induced Migration of Human Adipose-derived Stem Cells

  • Lim, Yoonhwa;Lee, Minji;Jeong, Hyeju;Kim, Haekwon
    • Development and Reproduction
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    • v.21 no.2
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    • pp.167-180
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    • 2017
  • Human adult stem cells have widely been examined for their clinical application including their wound healing effect in vivo. To function as therapeutic cells, however, cells must represent the ability of directed migration in response to signals. This study aimed to investigate the mechanism of platelet-derived growth factor (PDGF)-induced migration of the human abdominal adipose-derived stem cells (hADSCs) in vitro. A general matrix metalloproteinase (MMP) inhibitor or a MMP2 inhibitor significantly inhibited the PDGF-induced migration. PDGF treatment exhibited greater mRNA level and denser protein level of MMP1. The conditioned medium of PDGF-treated cells showed a caseinolytic activity of MMP1. Transfection of cells with siRNA against MMP1 significantly inhibited MMP1 expression, its caseinolytic activity, and cell migration following PDGF treatment. Phosphatidylinositol 3-kinase (PI3K) inhibitor reduced the migration by about 50% without affecting ERK and MLC proteins. Rho-associated protein kinase inhibitor mostly abolished the migration and MLC proteins. The results suggest that PDGF might signal hADSCs through PI3K, and MMP1 activity could play an important role in this PDGF-induced migration in vitro.

Metalloproteinase Plays a Role in Mucin Secretion (Mucin 분비에 영향을 미치는 Metalloproteinase)

  • Oh, Yeon-Mok;Choi, Hee Jin;Shim, Tae Sun;Lee, Sang Do;Kim, Woo Sung;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.3
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    • pp.289-296
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    • 2004
  • Background : Mucus hypersecretion in the patients with airway diseases represents poor prognosis as well as discomfort. However, there is no known therapy for its effective control. One important component of mucus is mucin, a glycosylated protein, which endows mucus with viscosity. We studied whether a proteinase has a role in mucin secretion and if so, which. Methods : (1) Inhibition of mucin secretion Group-specific proteinase inhibitors were tested to evaluate whether a proteinase belonging to a group of proteinases plays a role in mucin secretion. Phenylmethylsulfonyl fluoride(PMSF, a serine proteinase inhibitor), E-64(a cysteine proteinase inhibitor), Pepstatin(an aspartic proteinase inhibitor) and 1, 10-Phenanthroline(a metalloproteinase inhibitor) were treated into the Calu-3 cell line for 24 hours. The enzyme linked immunoabsorbant assay(ELISA) for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with a control. (2) Stimulation of mucin secretion Matrix metalloproteinase-9(MMP-9), MMP-12 and TACE(TNF-alpha converting enzyme), which are known to be related with airway diseases, were used to be treated into Calu-3 for 24 hours. ELISA for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with the controls. Results : (1) PMSF($10^{-4}M$), E-64($10^{-4}M$), Pepstatin($10^{-6}M$) and 1, 10-Phenanthroline($10^{-4}M$) reduced the MUC5AC secretion by $1{\pm}4.9%$(mean${\pm}$standard deviation; P=1.0 compared with the control), $-6{\pm}3.9%$(P=0.34), $-13{\pm}9.7%$(P=0.34) and $41{\pm}8.2%$(P=0.03), respectively. (2) The amounts of MUC5AC secretion stimulated by MMP-9(250ng/ml), MMP-12(100ng/ml) and TACE(200ng/ml) were $103{\pm}6%$(P=0.39), $102{\pm}8%$(P=1.0) and $107{\pm}13%$(P=0.39), respectively, compared with the controls. Conclusion : Metalloproteinase(s) is (are) suggested to play a role in mucin secretion. It appears that metalloproteinases, other than MMP-9, MMP-12 or TACE, affect the mucin secretion in this in vitro model.

Effect of Asterina pectinifera on Activities of Breast Cancer Chemopreventive and Metastatic Enzymes (별불가사리 단백추출물이 유방암예방 및 전이억제 효소계에 미치는 영향)

  • Nam, Kyung-Soo;Kim, Mee-Kyung;Cho, Hyun-Jung;Shon, Yun-Hee
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.3
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    • pp.193-197
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    • 2006
  • The effect of protein extract from Asterina pectinifera on breast cancer chemopreventive (aromatase and cyclooxygenase-2) and metastatic (matrix metalloproteinase) enzymes was tested. Protein extract from A. pectinifera was capable of suppressing aromatase in a human placenta microsomal assay. Cyclooxygenase-2 (COX-2) activity was significantly inhibited by the protein extract from A. pectinifera at concentrations of 10, 20 and $40{\mu}g/m{\ell}$. The extract markedly reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated matrix metalloproteinase (MMP)-9 activity. These results suggest that A. pectinifera could be of therapeutic value in preventing human breast cancer.

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Effect of Treponema lecithinolyticum lipopolysaccharide on matrix metalloproteinase-9 expression (Treponema lecithinolyticum lipopolysaccharide에 의한 matrix metalloproteinase-9의 발현)

  • Nam, Jeong-Ah;Moon, Sun-Young;Lee, Jin-Wook;Cha, Jeong-Heon;Choi, Bong-Kyu;Yoo, Yun-Jung
    • Journal of Periodontal and Implant Science
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    • v.35 no.3
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    • pp.675-685
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    • 2005
  • Bone resorption involves sequential stages of osteoclast precursor migration and differentiation of osteoclast precursors into multinucleated osteoclasts. Stromal cell derived factor (SDF)-1 is a chemotactic factor for osteoclast precursor migration. Matrix metalloproteinase (MMP)-9 is involved in migration of osteoclast precursors and activation of $interleukin(IL)-1{\beta}$. Alveolar bone destruction is a characteristic feature of periodontal disease. Treponema lecithinolyticum is a oral spirochete isolated from the periodontal lesions. The effect of lipopolysaccharide(LPS) from T. lecithinolyticum on expression of SDF-1 and MMP-9 was examined in cocultures of bone marrow cells and osteblasts derived from mouse calvariae. T. lecithinolyticum LPS increased expression of MMP-9 in the coculture. Polymyxin B, an inhibitor of LPS, abolished the increase of MMP-9 mRNA expression by LPS. LPS did not increase the expression of SDF-1, $IL-1{\beta}$ and tumor necrosis $factor(TNF)-{\alpha}$ mRNA in cocultures. Prostaglandin $E_2(PGE_2)$ up-regulated the expression of MMP-9 and NS398, an inhibitor of $PGE_2$ synthesis, down-regulated the induction of MMP-9 expression by T. lecitbinolyticm LPS. These results suggest that T. lecitbinolyticm LPS increases MMP-9 expression in bone cells via $PGE_2$ and that the induction of MMP-9 expression by T. lecitbinolyticm LPS is involved in alveolar bone destruction of periodontitis patients by the increase of osteoclast precursor migration and the activation of bone resorption-inducing cytokine.

Inhibitory effect of 2-amino-3-ethoxycarbonyl-1-methyl pyrolo (3,2-b) naphtho-4,9-dione on tumor cell invasion in human fibrosarcoma cells by downregulating matrix metalloproteinase-2 and 9

  • Park, Hyen-Joo;Hwang, Hye-Jin;Lee, Hyun-Jung;Suh, Myung-Eun;Lee, Sang-Kook
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.243.1-243.1
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    • 2002
  • Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis by matrix degradation. To analyze the effect of 2-amino-3-ethoxycarbonyl-1-methyl pyrolo (3,2-b) naphtho-4,9-dione (compound 1) on the invasion or metastasis of cancer cells the expression of matrix metalloproteases (MMPs) was investigated in human fibrosarcoma HT 1080 cells by AT -PCR or gelatin zymographic methods. (omitted)

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Clinical Implication of Aortic Wall Biopsy in Aortic Valve Disease with Bicuspid Valve Pathology

  • Kim, Yong Han;Kim, Ji Seong;Choi, Jae-Woong;Chang, Hyoung Woo;Na, Kwon Joong;Kim, Jun Sung;Kim, Kyung-Hwan
    • Journal of Chest Surgery
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    • v.49 no.6
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    • pp.443-450
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    • 2016
  • Background: Although unique aortic pathology related to bicuspid aortic valve (BAV) has been previously reported, clinical implications of BAV to aortopathy risk have yet to be investigated. We looked for potential differences in matrix protein expressions in the aortic wall in BAV patients. Methods: Aorta specimens were obtained from 31 patients: BAV group (n=27), tricuspid aortic valve (TAV) group (n=4). The BAV group was categorized into three subgroups: left coronary sinus-right coronary sinus (R+L group; n=13, 42%), right coronary sinus-non-coronary sinus (R+N group; n=8, 26%), and anteroposterior (AP group; n=6, 19%). We analyzed the expression of endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2. Results: Based on the mean value of the control group, BAV group showed decreased expression of eNOS in 72.7% of patients, increased MMP-9 in 82.3%, and decreased TIMP in 79.2%. There was a higher tendency for aortopathy in the BAV group: eNOS $(BAV:TAV)=53%{\pm}7%:57%{\pm}11%$, MMP-9 $(BAV:TAV)=48%{\pm}10%:38%{\pm}1%$. The AP group showed lower expression of eNOS than the fusion (R+L, R+N) group did; $48%{\pm}5%$ vs. $55%{\pm}7%$ (p=0.081). Conclusion: Not all patients with BAV had expression of aortopathy; however, for patients who had a suspicious form of bicuspid valve, aortic wall biopsy could be valuable to signify the presence of aortopathy.

The expressions of inflammatory factors and tissue inhibitor of matrix metalloproteinase-2 in human chronic periodontitis with type 2 diabetes mellitus

  • Shin, Dong-Seok;Park, Jin-Woo;Suh, Jo-Young;Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • v.40 no.1
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    • pp.33-38
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    • 2010
  • Purpose: The purpose of this study was to observe and quantify the expression of interleukin-4 (IL-4), interferon-$\gamma$ (IFN-$\gamma$), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the gingival tissue of patients with type 2 diabetes mellitus (DM) and healthy adults with chronic periodontitis. Methods: Twelve patients with type 2 DM and chronic periodontitis (Group 3), twelve patients with chronic periodontitis (Group 2), and twelve healthy individuals (Group 1) were included in the study. Clinical criteria of gingival (sulcus bleeding index value, probing depths) and radiographic evidences of bone resorption were divided into three groups. The concentrations of cytokines were determined by a western blot analysis and compared using one-way ANOVA followed by Tukey's test. Results: The expression levels of IFN-$\gamma$ and TIMP-2 showed an increasing tendency in Groups 2 and 3 when compared to Group 1. On the other hand, the expression of IL-4 was highest in Group 1. Conclusions: The findings suggest that IFN-$\gamma$ and TIMP-2 may be involved in the periodontal inflammation associated with type 2 DM. IL-4 may be involved in the retrogression of the periodontal inflammation associated with type 2 DM.

Sulforaphane Inhibits Ultraviolet B-induced Matrix Metalloproteinase Expression in Human Dermal Fibroblasts

  • Lee, Sam Youn;Moon, Sun Rock
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.6
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    • pp.922-928
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    • 2012
  • Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is one of the most abundant isothiocyanates in some cruciferous vegetables, especially broccoli. Sulforaphaene has been shown to exhibit many pharmacological activities, including anti-oxidant, anti-inflammatory and anti-microbial activities. However, the anti-skin photoaging effects of sulforaphane have not yet been reported. In the present study, we investigated the inhibitory effects of sulforaphane on MMP-1 and -3 expressions of the human dermal fibroblasts via various in vitro experiments and elucidated the pathways of inhibition. Western blot analysis and real-time PCR revealed sulfiraphane inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, which was determined by NF-${\kappa}B$ DNA binding activity. UVB-induced NF-${\kappa}B$ activation and MMP expression were completely blocked by sulforphane. These findings suggest that sulforaphane could prevent UVB-induced MMPs expressions through inhibition of NF-${\kappa}B$ activation.

The effect of tumor necrosis factor (TNF)-α to induce matrix metalloproteinase (MMPs) from the human dental pulp, gingival, and periodontal ligament cells (사람의 치수, 치은, 치주인대 세포에 tumor necrosis factor (TNF)-α로 자극 시 matrix metalloproteinase (MMPs)의 분비에 관한 연구)

  • Rhim, Eun-Mi;Park, Sang-Hyuk;Kim, Duck-Su;Kim, Sun-Young;Choi, Kyoung-Kyu;Choi, Gi-Woon
    • Restorative Dentistry and Endodontics
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    • v.36 no.1
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    • pp.26-36
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    • 2011
  • Objectives: In the present study, three kinds of tissues cells (pulp, gingiva, and periodontal ligament) were investigated if those cells express MMP and TIMP when they were stimulated with neuropeptides (substance P, CGRP) or proinflammatory cytokine, TNF-$\alpha$. Materials and Methods: The cells cultured from human dental pulp (PF), gingiva (GF) and periodontal ligament were (PDLF) stimulated with Mock, SP, TNF-$\alpha$, and CGRP for 24 hrs and 48 hrs. for an RNase protection assay and Enzyme Linked Immunosorbent Assay. Cells (PF, GF and PDLF) seeded in 100 mm culture dish were stimulated with SP ($10^{-5}$, $10^{-8}\;M$) or only with medium (Mock stimulation) for 4hrs and for 24 hrs for RNase Protection Assay, and they were stimulated with CGRP ($10^{-5}\;M$) and TNF-$\alpha$(2 ng/mL) for 24 hrs and with various concentraion of TNF-$\alpha$(2, 10, and 100 ng/mL) for Rnase Protection Assay with a human MMP-1 probe set including MMP 1, 2, 8, 7, 8, 9, 12, and TIMP 2, 3. In addition, cells (PF, GF and PDLF) were stimulated with Mock and various concentraion of TNF-$\alpha$(2, 10, and 100 ng/mL) for 24 hrs and with TNF-$\alpha$(10 ng/mL) for 48 hrs, and the supernatents from the cells were collected for Enzyme Linked Immunosorbent Assay (ELISA) for MMP-1 and MMP-13. Results: The expression of MMPs in PF, GF, PDLF after stimulation with SP and CGRP were not changed compared with Mock stimulation for 4 hrs and 24 hrs. The expression of MMP-1, -12, -13 24 hrs after stimulation with TNF-$\alpha$ were upregulated, however the expression of TIMP-3 in PF, GF, PDLF after stimulation with TNF-$\alpha$ were downregulated. TNF-$\alpha$(2 ng/mL, 10 ng/mL, 100 ng/mL) increased MMP-1 and MMP-12 expression in PF dose dependently for 24 hrs. Conclusions: TNF-$\alpha$ in the area of inflammation may play an important role in regulating the remodeling of dentin, cementum, and alveolar bone.