• Title/Summary/Keyword: Matrix metalloproteinase 14

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Preoperative Levels of Matrix Metalloproteinase-7 and -9 and Tissue Inhibitor of Matrix Metalloproteinase-1 Relation to Pathologic Parameters in Bladder Carcinoma Patients

  • Gunes, Mustafa;Kemik, Ahu Serap;Pirincci, Necip;Gecit, Ilhan;Taken, Kerem;Yuksel, Mehmet Bilgehan;Kaba, Mehmet;Eryilmaz, Recep
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.873-876
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    • 2013
  • Our aim was to test the hypothesis that preoperative serum levels of matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) levels correlate with pathological features. Serum levels of MMP-7, and MMP-9 and TIMP-1 were determined in 90 bladder cancer patients and 40 healthy controls using an enzyme linked immunosorbent assay. Preoperative serum MMP-7 and MMP-9 levels were significantly higher in cancer patients than control groups (p<0.001). In contast, serum TIMP-1 levels were lower (p<0.001). Alteration in MMP-7, and MMP-9, and TIMP-1 production may contribute to tumor angiogenesis and be associated with clinic-pathological features.

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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    • v.4 no.2
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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.

HISTOLOGICAL CHANGES AND EXPRESSION OF MATRIX METALLOPROTEINASE-2 AND TISSUE INHIBITOR OF MATRIX METALLOPROTEINASE-2 IN THE CANINE MANDIBULAR CONDYLE AFTER DISTRACTION OSTEOGENESIS (성견에서 하악골 신장술 후 하악과두 연골의 조직학적 변화와 Matrix Metalloproteinase-2 (MMP-2)와 Tissue Inhibitor of Matrix Metalloproteinase-2 (TIMP-2)의 발현)

  • Byun, June-Ho;Park, Bong-Wook;Cho, Yeong-Cheol;Sung, Iel-Yong;Son, Jae-Hee;Kim, Jong-Ryoul
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.5
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    • pp.404-416
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    • 2006
  • Purpose : This study was to clarify the changes in mandibular condyle after unilateral mandibular distraction osteogenesis throughout histological changes and expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2). Materials & Methods : Intraoral distractors were placed via submandibular incision in 8 dogs. Two unoperated animals served as controls. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. Two animals were sacrificed on 7, 14, 28, and 56 days after completion of distraction, respectively. Ipsilateral condyles were harvested and processed for histological and immunohistochemical examinations. Results : The condyle cartilage is separated into four layers: fibrous layer, proliferative layer, hypertrophic layer, and calcified layer. At 7 days and 14 days after distraction, the condylar cartilage showed the decreased thickness of the articular cartilage and reduced cellularity. At 28 days after distraction, there was an increase in cellularity of fibrous, proliferative, and hypertrophic layer. However, it demonstrated reduced cellularity compared to the control. At 56 days of after distraction, the articular cartilage was an almost normal histologic structure. Positive Safranin-O staining, indicative of sulfated proteoglycans, was examined in the condylar cartilge of nonloaded control. At 7 days and 14 days after distraction, the sulfated proteoglycans is almost completely depleted from the noncalcified part of the condylar cartilage. At 28 days after distraction, there was an increase in Safranin-O staining intensity. However, the staining intensity of the experimental condyle was weaker than that of the control. At 56 days of after distraction, the condylar cartilage showed almost normal Safranin-O staining pattern. In control condyle, MMP-2 immunostaining was seen in fibrous, proliferative, and hypertrophic layer of condylar cartilage, however, it demonstrated lack of staining in fibrous and proliferative layer. At 7 days and 14 days after distraction, strong MMP-2 immunoreactivity was seen in the fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 28 days after distraction, MMP-2 immunostaining was seen in the fibrous and hypertrophic layer of condylar cartilage, however, their immunoactivity was reduced. At 56 days after distraction, MMP-2 immunoreactivity showed almost normal immunostaining pattern. In control condyle, TIMP-2 immunostaining was primarily seen in fibrous and hypertrophic layer of condylar cartilage, however, it demonstrated lack of staining in proliferative layer. At 7 days after distraction, very weak TIMP-2 immunoreactivity appeared in fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 14 days after distraction, weak TIMP-2 immunoreactivity was seen in the fibrous, proliferative and hypertrophic layer of the condylar cartilage. At 28 days after distraction, TIMP-2 immunoreactivity was increased in the fibrous and hypertrophic layer of condylar cartilage. At 56 days after completion of distraction, TIMP-2 immunoreactivity showed almost normal immunostaining pattern. Conclusions : The results show that short-term outcome of physiologic distraction osteogenesis may lead to degenerative changes in the condylar cartilage. These alterations in the condylar cartilage may be considered as a pressure-related degeneration of the cartilage tissue. However, the long-term results suggest that the condylar cartilage display repair activity after mandibular distraction osteogenesis.

Overexpression of Twist and Matrix Metalloproteinase-9 with Metastasis and Prognosis in Gastric Cancer

  • Gao, Xing-Hui;Yang, Xue-Qin;Wang, Bi-Cheng;Liu, Shao-Ping;Wang, Fu-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5055-5060
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    • 2013
  • Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. Methods:Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopatholgic features and to patients' outcome. Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.

Inhibitory Effect of Gallic Aicd on TNF-α-induced matrix metalloproteinase-1 (MMP-1) in HaCaT Cells (HaCaT세포에서 TNF-α에 의해 유도되는 MMP-1에 대한 Gallic Aicd의 저해 효과)

  • Kim, Pom-Ho
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.14 no.11
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    • pp.5778-5784
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    • 2013
  • In order to develop anti-wrinkle agent, we measured the anti-oxidative activity of gallic acid (GA) from Paeonia suffruticosa Andrews and investigated its cytotoxicity in HaCaT cells and then investigated its effect on tumor necrosis factor alpha (TNF-${\alpha}$)-induced matrix metalloproteinase-1 (MMP-1) mRNA, protein expressions and secretion in same cells. GA showed anti-oxidative activity with $IC_{50}$ of 30 ${\mu}g/mL$ and its activity was higher than that of butylated hydroxyanisol (BHA). GA showed weak cytotoxicity with high concentration (200 ${\mu}g/mL$) in HaCaT cells. MMP-1 mRNA, protein expression and secretion induced by tumor necrosis factor alpha (TNF-${\alpha}$) in HaCaT cells were significantly decreased by treatment of GA with dose-dependent manner(p<0.05). Therefore, our findings suggest that GA can be useful as an active ingredient for cosmeceuticals of anti-wrinkle effects.

12-Oxoeicosatetraenoic acid, a candidate signal for placenta separation, activates matrix metalloproteinase and induces apoptosis in bovine trophoblast cells

  • Hachiro Kamada
    • Animal Bioscience
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    • v.36 no.3
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    • pp.429-440
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    • 2023
  • Objective: 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-KETE), a metabolite of arachidonic acid, is a strong candidate signal for placenta separation following calf discharge at delivery. In the present study, the effects of 12-KETE on bovine trophoblast cells were investigated to determine its function in the placentome at delivery. Methods: Bovine trophoblast cells derived from blastocysts were used. They were cocultured with or without fibroblasts derived from bovine placentome and/or bovine uterine epithelial cells. 12-KETE was added to the culture medium. Results: Bovine trophoblast cells contained binucleate cells and strongly expressed caudal type homeobox 2 (CDX-2) genes. Addition of 12-KETE to the trophoblast cell colony without feeder cells or that on a fibroblast monolayer induced rapid exfoliation of the colony. After 12-KETE addition, trophoblast cells emitted strong fluorescence caused by the degradation of dye-quenched collagen, indicating that 12-KETE activated matrix metalloproteinase of the trophoblast cells. Exfoliated cell colonies were stained with YOPRO-1, but not propidium iodide (PI). Moreover, DNA fragmentation and Bcl-2 associated X protein (Bax) gene (apoptosis stimulator) upregulation were observed in exfoliated cells, indicating that 12- KETE induced trophoblast cell apoptosis. These results were consistent with previous in vivo observations; however, even a lower concentration of 12-KETE activated trophoblast protease. Meanwhile, fibroblasts derived from the bovine placentome converted arachidonic acid to 12-KETE. Conclusion: These observations indicate that 12-KETE may serve as a signal for placenta separation at delivery.

Overexpression of Matrix Metalloproteinase 11 in Thai Prostatic Adenocarcinoma is Associated with Poor Survival

  • Nonsrijun, Nongnuch;Mitchai, Jumphol;Brown, Kamoltip;Leksomboon, Ratana;Tuamsuk, Panya
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3331-3335
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    • 2013
  • Background: The incidence of prostate cancer, one of the most common cancers in elderly men, is increasing annually in Thailand. Matrix metalloproteinase 11 (MMP-11) is a member of the extracellular matrix metalloproteases which has been associated with human tumor progression and clinical outcome. Aim: To quantify MMP-11 expression in prostatic adenocarcinoma tissues and to determine whether its overexpression correlates with survival outcome, and to assess its potential as a new prognostic marker. Materials and Methods: Expression of MMP-11 was analyzed using immunohistochemistry in 103 Thai patients with prostatic adenocarcinoma. Overall survival was analyzed using Kaplan-Meier methods and Cox regression models. Results: Immunoreactivity of MMP-11 was seen in the stroma of prostatic adenocarcinoma tissue samples, high expression being significantly correlated with poor differentiation in Gleason grading, pathologic tumor stage 4 (pT4), and positive-bone metastasis (p<0.05), but not age and prostatic-specific antigen (PSA) level. Patients with high levels of MMP-11 expression demonstrated significantly shorter survival (p<0.001) when compared to those with low levels. Multivariate analysis showed that MMP-11 expression and pT stage were related with survival in prostatic adenocarcinoma [hazard ratio (HR)=0.448, 95% confidence interval (95%CI)=0.212-0.946, HR=0.333, 95%CI=0.15-0.74, respectively]. Conclusions: Expression of MMP-11 is significantly associated with survival in prostatic adenocarcinoma. High levels may potentially be used for prediction of a poor prognosis.

The influence of type 2 diabetes mellitus on the expression of inflammatory mediators and tissue inhibitor of metalloproteinases-2 in human chronic periodontitis

  • Kim, Jae-Bung;Jung, Mi-Hwa;Cho, Je-Yeol;Park, Jin-Woo;Suh, Jo-Young;Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • v.41 no.3
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    • pp.109-116
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    • 2011
  • Purpose: The purpose of this study was to compare and quantify the expression of C-reactive protein (CRP), matrix metalloproteinase (MMP)-14, and tissue inhibitor of metalioproteinases (TIMP)-2 in gingival tissues of patients with chronic periodontitis accompanied with inflammatory reaction related to alveolar bone resorption with or without type 2 diabetes mellitus (DM). 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. Gingival tissue biopsies were collected from each patient and from healthy individuals at the time of periodontal surgery (including surgical crown lengthening) or tooth extraction. The concentrations of cytokines were determined by a western blot analysis. Results: The expression levels of CRP and MMP-14 increased in group 2 and 3, and they were highest in group 3. The expressions of TIMP-2 also increased in group 2 and 3. Conclusions: This study demonstrated that the expression levels of CRP, MMP-14, and TIMP-2 might be inflammatory markers in periodontal inflamed tissue. It can be assumed that CRP, MMP-14, and TIMP-2 may be partly involved in the progression of periodontal inflammation associated to type 2 DM.

Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gingival and periodontal ligament fibroblasts treated with lipopolysaccharide from Prevotella intermedia (Prevotella intermedia의 세균내독소가 치은섬유아세포와 치주인대세포에서의 matrix metalloproteinase 및 tissue inhibitor of metalloproteinase의 발현에 미치는 영향)

  • Kim, Sung-Jo;Choi, Eun-Young;Choi, In-Soon;Lee, Ju-Youn;Choi, Jeom-Il;Kim, Chong-Kwan
    • Journal of Periodontal and Implant Science
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    • v.35 no.1
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    • pp.21-30
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    • 2005
  • Matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes and implicated in the remodeling and degradation of extracellular matrix under both physiological and pathological conditions. Connective tissue degradation in periodontal diseases is thought to be due to excessive MMP activities over their specific inhibitors. The effects of lipopolysaccharide (LPS) from Prevotella intermedia, one of the major putative pathogens of periodontitis, on the expression of mRNA for MMPs and tissue inhibitors of metalloproteinases (TIMPs) in human gingival and periodontal ligament fibroblasts were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of mRNAs encoding MMP-1, -2, -3, -10, and -14 was increased in human gingival fibroblasts treated with p. intermedia LPS, whereas MMP-11 and TIMP-2 mRNA expression was decreased in these cells stimulated with LPS. P. intermedia LPS increased the MMP-1, -2, -10, -11, and -14 mRNA expression and decreased TIMP-1 and -2 mRNA expression in human periodontal ligament fibroblasts. These findings imply that P. intermedia LPS may play an important role in the connective tissue degradation in periodontitis.

Expression of RECK and MMPs in Hepatoblastoma and Neuroblastoma and Comparative Analysis on the Tumor Metastasis

  • Xu, Meng;Wang, Hai-Feng;Zhang, Huan-Zhi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.4007-4011
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    • 2015
  • Objective: To explore the expression of RECK and relevant matrix metalloproteinases (MMPs) in hepatoblastoma (HB) and neuroblastoma (NB) and their clinical significance in the tumor metastasis. Materials and Methods: Forty-five wax-stone samples of HB and 43 wax-stone samples of NB removed by surgical resection and confirmed by pathology in Linyi Yishui Central Hospital were selected. According to presence and absence of metastasis, both NB and HB samples were divided into metastatic group and non-metastatic group, namely NB metastatic group (n=28), NB non-metastatic group (n=15), HB metastatic group (n=15) and HB non-metastatic group (n=30). The expression of RECK, membrane type-1 matrix metalloproteinase (MT1-MMP) in HB tissue and RECK, MMP-14 in NB tissue was detected using immunohistochemical method, and the correlation between RECK and MT1-MMP, MMP-14 was analyzed. Results: The metastatic rate of NB was dramatically higher than that of HB, with statistical significance (P=0.003). The positive rate of RECK expression in NB group (30.2%) was slightly lower than in HB group (40.0%), but no significant difference was presented (P=0.338). The positive rate of MMPs expression in NB metastatic group was evidently higher than in HB metastatic group (P=0.024). The results of Spearman correlation analysis revealed that the expression of RECK in HB and NB tissues had a significantly-negative correlation with MT1-MMP and MMP-14, respectively (r=-0.499, P=0.012; r=-0.636, P=0.000). Conclusions: In HB and NB tissues, RECK is expressed lowly, while relevant MMPs highly, and RECK inhibits the tumor invasion and metastasis through negative regulation of relevant MMPs.