• Title, Summary, Keyword: MMP-7

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Role of MAP kinase on MMP-13 expression in rat periodontal ligament cells (백서 치주인대세포에서의 MMP-13 mRNA에 대한 MAP kinase의 역할)

  • Chung, Chan-Gil;Cui, De-Zhe;Chung, Hyun-Ju;Kim, Young-Joon
    • Journal of Periodontal and Implant Science
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    • v.36 no.1
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    • pp.85-96
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    • 2006
  • Matrix metalloproteinases (MMPs)는 치주조직내에 존재하는 세포외기질의 유지와 분해에 중요한 역할을 담당하고 있으며 이중 MMP-13은 치주질환의 진행과 깊은 관계가 있다고 알려져 있다. 이번 연구는 치주질환의 진행에 있어서 MMP-13의 활성에 대한 mitogen activated protein(MAP) Kinase의 역할을 구명하기 위해 시행되었다. 백서 치주인대세포에서의 MMP-13 mRNA의 발현은 RT-PCR에 의하여, 그리고 MAP Kinase의 발현은 Western blot에 의하여 측정하였다. $Interleukin-1{\beta}$(IL $-1{\beta}$), Tumor necrosis $factora(TNF-{\alpha})$와 parathyroid hormon(PTH)는 MMP- 13 mRNA 발현을 각각 320%, 180%, 380% 증가시켰으나 bone morphogenetic protein-7(BMP-7)은 MMP-13 mRNA의 발현을 증가시키지 않았다. p38 MAP Kinase 억제제인 SB203580은 IL $-1{\beta}$ 유도 MMP-13의 발현을 약 40% 정도 억제시켰으나, PTH-유도 MMP-13 mRNA의 발현은 억제하지 못했다. IL $-1{\beta}$는 MMP- 13 mRNA의 반감기를 약 2시간 정도로 증가시켰으나, p38 MAP Kinase 억제제로 전처치한 경우에는 반감기가 60분으로 줄어들었다. $IL-1{\beta}$는 p38 MAP kinase와 JNK의 인산화 활성을 증가시켰으나 PTH, $TNF-{\alpha}$와 BMP-7은 p38, JNK, ERK의 활성을 증가시키지 못했다. 이상의 연구결과는 p38 MAP Kinase가 백서 치주인대세포에서의 MMP-13 mRNA 발현을 조절하는데 중요한 역할을 담당함을 시사하였다.

MiR-886-5p Inhibition Inhibits Growth and Induces Apoptosis of MCF7 Cells

  • Zhang, Lei-Lei;Wu, Jiang;Liu, Qiang;Zhang, Yan;Sun, Zhu-Lei;Jing, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1511-1515
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    • 2014
  • Background and Aims: To explore the molecular mechanisms of miR-886-5p in breast cancer., we examined roles in inhibiting growth and migration of MCF-7 cells. Methods: MiR-886-5p mimics and inhibitors were used to express or inhibit MiR-886-5p, respectively, and MTT and clone formation assays were used to determine the survival and proliferation. Hoechst 33342/ PI double staining was applied to detect apoptosis. The expression of caspase-3, caspase-8, caspase-9, MT1-MMP, VEGF-C and VEGF-D was detected by Western blotting, and the levels of MMP2 and MMP9 secreted from MCF-7 cells were assessed by ELISA. MCF-7 cell migration was determined by wound healing and Transwell assays. Results: We found that the growth of MCF-7 cells was inhibited upon decreasing miR-886-5p levels. Inhibiting miR-866-5p also significantly induced apoptosis and decreased the migratory capacity of these cells. The expression of VEGF-C, VEGF-D, MT1-MMP, MMP2, and MMP9 was also found to be decreased as compared to controls. Conclusions: Our data show that downregulation of miR-886-5p expression in MCF-7 cells could significantly inhibit cell growth and migration. This might imply that inhibiting miR-886-5p could be a therapeutic strategy in breast cancer.

Tetrabromobisphenol A Induces MMP-9 Expression via NADPH Oxidase and the activation of ROS, MAPK, and Akt Pathways in Human Breast Cancer MCF-7 Cells

  • Lee, Gi Ho;Jin, Sun Woo;Kim, Se Jong;Pham, Thi Hoa;Choi, Jae Ho;Jeong, Hye Gwang
    • Toxicological Research
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    • v.35 no.1
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    • pp.93-101
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    • 2019
  • Tetrabromobisphenol A (TBBPA), the most common industrial brominated flame retardant, acts as a cytotoxic, neurotoxic, and immunotoxicant, causing inflammation and tumors. However, the mechanism of TBBPA-induced matrix metalloproteinase-9 (MMP-9) expression in human breast cancer cells is not clear. In human breast cancer MCF-7 cells, treatment with TBBPA significantly induced the expression and promoter activity of MMP-9. Transient transfection with MMP-9 mutation promoter constructs verified that $NF-{\kappa}B$ and AP-1 response elements are responsible for the effects of TBBPA. Furthermore, TBBPA-induced MMP-9 expression was mediated by $NF-{\kappa}B$ and AP-1 transcription activation as a result of the phosphorylation of the Akt and MAPK signaling pathways. Moreover, TBBPA-induced activation of Akt/MAPK pathways and MMP-9 expression were attenuated by a specific NADPH oxidase inhibitor, and the ROS scavenger. These results suggest that TBBPA can induce cancer cell metastasis by releasing MMP-9 via ROS-dependent MAPK, and Akt pathways in MCF-7 cells.

Effect of Anti-oxidant, Anti-inflammatory and Anti-invasive of PMA-induced Matrix Metalloproteinase (MMP-2) and MMP-9 Activities of Water Extract and Solvent Fractions of Saururus Chinensis (삼백초 물 추출물과 유기용매 분획물의 항산화, 항염증 및 PMA에 의해 유도된 MMP-2 및 MMP-9활성 침윤 억제 효과)

  • Kim, Jun-Ho;Kim, Eun-Jung
    • Journal of Life Science
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    • v.26 no.5
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    • pp.584-591
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    • 2016
  • Saururus chinensis is a perennial plants, its flavonoid compound is known to exhibit anti-oxidative activity. This study was aimed to investigate the effect of Water Extract and Solvent Fractions of Saururus chinensis on antioxidant, anti-inflammatory and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities. Plant samples were fractionated into hexane, CHCl3, ethyl acetate, butanol, and water fractions, and each of these was assayed individually. The water fraction showed the highest extraction yield at 9.25%(w/w). Anti-oxidative activity was analyzed by DPPH assay. Cell viability was detected by the MTS assay. Anti-inflammatory activity was assayed by the nitric oxide (NO) production in mouse macrophage Raw 264.7 cells. The activity and mRNA expression of MMP-2 and MMP-9 in human oral squamous carcinoma YD-10B cells were examined by zymography and RT-PCR. As results, MMP-2/-9 activation was increased in PMA induced YD-10B cells. In PMA-treated YD-10B cells, the increased mRNA expression and protein activation of MMP-2/-9 were significantly inhibited in the ethyl acetate fraction. The ethyl acetate fraction showed the highest anti-oxidative activity at 73.38%. The ethyl acetate fraction at non-cytotoxic concentrations significantly exhibited the anti-inflammatory activity of Raw 264.7 cells in dose-dependent manner. In conclusion, these findings demonstrate that the ethyl acetate fraction obtained from a chinensis water extract potentiates a promising therapeutic anti-invasive agent and, therefore, as an anti-cancer drug for cancer prevention and therapy in oral cancer.

Comparison of Effects between Alteplase and Pamiteplase on MMPs Regulation (Alteplase와 pamiteplase에 의한 MMPs 조절 효과 비교)

  • Jung, Jae-Chang;Lee, Sun-Ryung
    • Journal of Life Science
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    • v.17 no.7
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    • pp.1019-1022
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    • 2007
  • Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.

The MMP-2 -735 C Allele is a Risk Factor for Susceptibility to Breast Cancer

  • Yari, Kheirollah;Rahimi, Ziba;Moradi, Mohamad Taher;Rahimi, Zohreh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6199-6203
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    • 2014
  • Background: The expression of MMP genes has been demonstrated to be associated with tumor invasion, metastasis and survival rate for a variety of cancers. The functional promoter polymorphism MMP-2 C-735T is associated with decreased expression of the MMP-2 gene. The aim of present study was to detect any association between MMP-2 C-735T and susceptibility to breast cancer. Materials and Methods: The MMP-2 C-735T polymorphism was studied in 233 women (98 with breast cancer and 135 healthy controls). All studied women were from Kermanshah and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MMP-2 CC, CT and TT genotypes in healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed (p=0.077). In patients the frequency of the MMP-2 C allele was significantly higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI 1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in patients ${\leq}40$ years (88.9%) than those aged ${\geq}41$ years (67.5%, p=0.07). In addition, the frequency of MMP-2 C allele tended to be higher in patients with a family history of cancer in first-degree relatives (76.6%) compared to that without a family history of cancer (67.3%, p=0.31). Conclusions: Our findings indicate that the C allele of MMP-2 C-735T polymorphism is associated with increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk of young onset breast cancer in our population.

NF-κB-dependent Regulation of Matrix Metalloproteinase-9 Gene Expression by Lipopolysaccharide in a Macrophage Cell Line RAW 264.7

  • Rhee, Jae-Won;Lee, Keun-Wook;Kim, Dong-Bum;Lee, Young-Hee;Jeon, Ok-Hee;Kwon, Hyung-Joo;Kim, Doo-Sik
    • BMB Reports
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    • v.40 no.1
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    • pp.88-94
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    • 2007
  • Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in the turnover of extracellular matrix (ECM) and in the migration of normal and tumor cells in response to normal physiologic and numerous pathologic conditions. Here, we show that the transcription of the MMP-9 gene is induced by lipopolysaccharide (LPS) stimulation in cells of a macrophage lineage (RAW 264.7 cells). We provide evidence that the NF-$\kappa$B binding site of the MMP-9 gene contributes to its expression in the LPS-signaling pathway, since mutation of NF-$\kappa$B binding site of MMP-9 promoter leads to a dramatic reduction in MMP-9 promoter activation. In addition, the degradation of l$\kappa$B$\alpha$;, and the presences of myeloid differentiation protein (MyD88) and tumor necrosis factor receptor-associated kinase 6 (TRAF6) were found to be required for LPS-activated MMP-9 expression. Chromatin immunoprecipitation (ChIP) assays showed that functional interaction between NF-$\kappa$B and the MMP-9 promoter element is necessary for LPS-activated MMP-9 induction in RAW 264.7 cells. In conclusion, our observations demonstrate that NF-$\kappa$B contributes to LPS-induced MMP-9 gene expression in a mouse macrophage cell line.

Influence of Smoking on Matrix Metalloproteinase-9 in the Gingival Crevicular Fluid (흡연이 치은열구액 내 Matrix Metalloproteinase-9에 미치는 영향)

  • Hwang, Soo-Jeong;Kim, Young-Kwon;Yang, Seong-Ju;Cho, Hyun-Jeong
    • Journal of dental hygiene science
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    • v.11 no.4
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    • pp.339-344
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    • 2011
  • Matrix metalloproteinase(MMP)-9 is considered important in tissue destruction in periodontitis. The aim of this study was to investigate the influence of smoking on MMP-9 in the gingival crevicular fluid(GCF). GCF samples in upper incisors area from 332 male subjects were collected after the informed consent. The dental examination included the assessment of oral hygiene, gingival inflammation and probing pocket depth. A quantitative assessment of MMP-9 levels in GCF was performed utilizing and immunological procedure. The mean MMP-9 concentrations found in GCF of smokers(30.86 ng/ml) and quit-smokers(29.82 ng/ml) differed from non-smokers(11.33 ng/ml), adjusted by age, gingival index and Community periodontal index(p<0.001). Smoking seems to influence MMP-9 in GCF regardless of gingival inflammation and age. It means smoking can destruct the periodontal tissue for itself.

The Effects of Paeonia Lactiflora Pallas on Inhibition of Oxygen Free Radical, Anti-inflammation and MMP-1 Inhibitory Activity (적작약 꽃 추출물의 활성산소 억제와 항염증 및 MMP-1 발현 억제능 효과에 관한 연구)

  • Leea, Jae-Nam;Kim, Young-Sam
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.3
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    • pp.797-806
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    • 2018
  • This study attempted to investigate the effects of Paeonia Lactiflora Pallas (P. lactiflora) on the inhibition of oxygen free radical, anti-inflammation and MMP-1 inhibitory activity and examine its possibility as a functional cosmetic material. For test methods, the inhibition of oxygen free radical after measuring reactive oxygen species (ROS) in the cell, cytotoxicity assessment and anti-inflammation were measured, and MMP-1 inhibitory effects in the HDF cell were measured. According to the test, the inhibition of ROS was confirmed in RAW 264.7 and HDF cells. In terms of cytotoxicity assessment, 90% or higher cell viability was detected at $5/10{\mu}g/mL$ Paeonia Lactiflora Pallas extract while it was 80% or higher at other concentration levels in both RAW 264.7 and HDF cells. In addition, NO production was inhibited in the RAW 264.7 cell while MMP-1 was significantly inhibited in the HDF cell. The above results reveal a possibility of Paeonia Lactiflora Pallas extract as a functional cosmetic material after confirming the inhibition of ROS synthesis in the cell, antioxidant and anti-inflammatory effects by inhibiting NO synthesis, low toxicity on skin cells and anti-aging effect through MMP-1 inhibition.

Up-regulation of Matrix Metalloproteinase-9 in Smooth Muscle Cell Undergoing Death (사멸세포에서의 metalloproteinase-9의 작용)

  • Lee, Kyeong-Ah;Kim, Sun-Mi;Kim, Koan-Hoi
    • Journal of Life Science
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    • v.16 no.7
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    • pp.1229-1234
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    • 2006
  • This study investigated whether matrix metalloproteinases (MMPs) can be modified in apoptotic smooth muscle cell (SMC) using the SMC that undergoes apoptotic death by expressing Fas-associated death domain containing protein (FADD) when they are grown without tetracycline in culture medium. In the absence of tetracycline, FADD-SMC lost adherence and showed the fragmentation of the nuclei. In proportion to duration of tetracycline removal, phosphorylated form of p38 MAPK and of ERK increased, whereas phosphorylation of protein kinase B (PKB) was not changed very much in response to tetracycline The levels of cyclin A and cyclin D were also decreased in a time dependent manner. Up-regulation of MMP-9 expression and activity was observed when the SMC were grown without tetracycline. Immunoreactivity of MMP-9 was detected from both attached and floating FADD-SMCs grown without tetracycline. An inhibitor of MAPK kinase, PD098059, and an inhibitor of p38 MAPK, SB203580, inhibited the up-regulation of MMP-9. Treatment of the SMC with a synthetic MMP inhibitor, BB94, attenuated death occurring in the absence of tetracycline. These results indicate that SMC undergoing death is able to up-regulate MMP-9 and that the enzyme can affect cell viability.