• Title/Summary/Keyword: MMP-8

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ROLE OF NF${\kappa}B$ IN TOLL-LIKE RECEPTOR 9-MEDIATED MATRIX METALLOPROTEINASE-9 EXPRESSION (Toll-like receptor 9-매개에 의한 matrix metalloproteinase-9 발현에서 NF${\kappa}B$의 역할)

  • Lee, Sang-Hoon;Chin, Byung-Rho;Baek, Suk-Hwan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.6
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    • pp.636-642
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    • 2007
  • Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.

3,9-Diferuloyl-6-oxopterocarpen (Tensolin-F$^\circledR$): a Novel Anti-wrinkle Agent for Cosmeceuticals (새로운 주름개선 소재: 3,9-diferuloyl-6-oxopterocarpen (Tensolin-F$^\circledR$)의 개발과 화장품 응용)

  • 이범천;이정재;박성민;김철배;심관섭;김진화;이근수;이천일;표형배
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.1
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    • pp.7-13
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    • 2004
  • As a novel anti-wrinkle agent, 3,9-diferuloyl-6-oxopterocarpen (Tensolin-F$^{(R)}$) has been synthesized and its anti-aging effects have been investigated. In the present study, to investigate the relationship between aging and Tensolin-F$^{(R)}$, we examined its effect on scavenging activities of radicals and reactive oxygen species (ROS), in vitro inhibition activity of matrix-metalloproteinase (MMP) and expression of UVA-induced MMPs in human dermal fibroblasts (HDF). Tensolin-F$^{(R)}$ was found to show activities of scavenging radicals and ROS with the $IC_{50}$/ values of 0.2 mM and 0.95 mM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide radicals, respectively, in the xanthine/xanthine oxidase system. Fluorometric assays for the proteolytic activities of MMP-l (collagenase) were performed using fluorescent collagen substrates. Tensolin-F$^{(R)}$ inhibited the activities of MMP-l in a dose-dependent manner and the $IC_{50}$/ values calculated from semi-log plots were 0.025 mM. Also, UVA induced MMP-1 expression was reduced 85% by treatment with Tensolin-F$^{(R)}$ at 0.8 uM, which was reduced dose-dependent manner. The results of clinical study showed that 4.8 mM Tensolin-F$^{(R)}$ treated group reduced wrinkle significantly compared with placebo treated group (P 〈 0.05). Taken together, these result suggest that Tensolin-F$^{(R)}$ act as an anti-wrinkle agent by taking effects to antioxidation and reducing UVA-induced MMP-l production.-l production.

Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 levels in Exudative Pleural Effusions (삼출성 흉수에서 기질 금속단백분해효소-1과 금속단백분해효소의 조직억제제-1)

  • Cho, Jae Hwa;Nam, Jeong Hyeon;Lee, Kyum Ho;Yoon, Byeong Kab;Ryu, Jeong Sun;Kwak, Sung Min;Lee, Hong Lyeol
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.5
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    • pp.517-521
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    • 2005
  • Background : The balances of the proteinases and antiproteinases system have been implicated in the pathogenesis of various exudative pleural effusions. The aim of this study was to examine the matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in exudative pleural effusions. Methods : The study included 33 tuberculous effusions, 17 malignant, and 5 transudates. The pleural levels of MMP-1 and TIMP-1 were determined using a commercially available ELISA assay. Results : The group of tuberculous effusions showed higher pleural MMP-1 levels than the malignant and transudates. The pleural TIMP-1 levels of the tuberculous and malignant effusions were higher than the transudates. Conclusion : Elevated pleural MMP-1 and TIMP-1 levels were found in tuberculous effusions.

Expression of Membrane-Type Matrix Metalloproteinase 1 and 2 in Mouse Oocytes, Embryos, Ovary and Oviduct (생쥐 난자와 배아 및 난소와 수란관의 Membrane-Type Matrix Metalloproteinase 1 및 2의 유전자 발현)

  • 김지영;이희진;김소라;김해권;강성구;이승재;조동제
    • Development and Reproduction
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    • v.4 no.1
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    • pp.45-52
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    • 2000
  • Membrane type matrix metalloproteinases(MT-MMPs) have been suggested to play an important role during structural remodeling of various tissue. Expression patterns of MT1-MMP and MT2-MMP mRNAs were investigated in oocytes, embryos, ovary and oviduct of mouse during their differentiation or periovulatory period using RT-PCR technique. Both cDNA products of MT1- and MT2-MMP of immature oocytes were barely discernable with a minimum amount but the expressions were distinct in mature oocytes regardless that they were matured in vivo or in vitro. MT2-MMP was not expressed by 2-cell embryos but was expressed by 4-cell stage embryos. From the morula stage untill hatched blastocyst stage, embyos showed intesnse expression of MT2-MMP with a sudden increase at blastocyst stage. While mouse ovarian tissues showed both expression of MT1- and MT2-MMP, there was no stage-specific difference throughout the estrous cycle. Mouse oviducts also exhibit constant amount of both MT1- and MT2-MMP expressions throughout periovulatory period, i.e., before or after ovulation. These observations lead to suggest that the differential expressions of maternal MT1- and MT2-MMP during meiotic resumption of mouse oocytes and embryonic expression of MT2-MMP particularly at blastocyst stage might play a role in the differentiation of mouse oocytes and/or embryos. The precise function of MT1- and MT2-MMP with regards to their participation in the remodeling of ovarian and oviductal tissues remains in a question.

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Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption

  • Kim, Seong-Gon;Kim, Myung-Hee;Chae, Chang-Hoon;Jung, Youn-Kwan;Choi, Je-Yong
    • BMB Reports
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    • v.41 no.4
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    • pp.322-327
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    • 2008
  • In this study, we compared the gene expression profiles of non-syndromic hyperplastic dental follicle (HDF) fibroblasts and normal dental follicle (NDF) fibroblasts using cDNA micro-arrays, quantitative PCR, and immunohistochemical staining. Microarray analysis showed that several collagens genes were upregulated in the HDF's, including collagen types I, IV, VIII, and XI and TIMP-1, -3, and -4 (fold ratio > 2.0). In contrast, the expression of MMP-1, -3, -10, and -16 together with IL-8 was more than two fold downregulated. The differential expression of the genes encoding alkaline phosphatase, MMP-1, -3, -8, and IL-8 was confirmed by quantitative RT-PCR, while that of 24 HDFs and 18 NDFs was confirmed by immunohistochemical analysis. However, HDFs showed stronger expression of MMP-3 than NDFs (P < 0.001). Collectively, these results indicate that defective regulation of MMPs mediating connective tissue remodeling may be responsible for abnormal tooth eruption.

Matrix Metalloproteinase-9 -1562T Allele and its Combination with MMP-2 -735 C Allele are Risk Factors for Breast Cancer

  • Rahimi, Zohreh;Yari, Kheirolah;Rahimi, Ziba
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1175-1179
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    • 2015
  • Background: Expression of matrix metalloproteinases (MMPs) is up-regulated in human cancers. The aim of present study was to investigate the role of MMP-9 C-1562T polymorphism and its interaction with MMP-2 C-735T polymorphism in susceptibility to breast cancer in a population from Western Iran with Kurdish ethnic background. Materials and Methods: The study sample of 205 individuals consisted of 101 breast cancer patients and 104 healthy subjects. MMP-9 C-1562T and MMP-2 C-735T variants were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Among 67.4% of studied patients the breast cancer developed in the third and forth decades of the life. The frequency of MMP-9 T allele was 17.3% in patients and 10.1% in controls. The presence of T allele significantly increased the risk of breast cancer by 1.87-fold [OR=1.87 (95% CI 1.05-3.33, p=0.035)]. The frequency of MMP-9 CT+TT genotype tended to be higher in those patients with a family history of cancer in first degree-relatives (36.8%) than those without a family history (28.3%, p=0.37). We observed an interaction between the MMP-9 -1562 T allele with MMP-2 -735 C allele that significantly increased the risk of breast cancer [OR=1.42 (95% CI 1.02-1.98, p=0.036)]. Conclusions: The present study demonstrated that MMP-9 C-1562T polymorphism alone and in combination with MMP-2 C-735T polymorphism increased the risk of breast cancer that might be a useful biomarker in identifying women at risk of developing breast cancer. Also, this study revealed that in most women from Western Iran breast cancer presents in third and fourth decades of life.

The effect of indomethacin on the matrix metalloproteinases in canine permanent tooth eruption (인도메타신의 투여가 치아 맹출 시 기질금속단백분해 효소의 분포에 미치는 영향)

  • Kang, Yoon-Goo;Nam, Jong-Hyun;Lee, Ki-Soo
    • The korean journal of orthodontics
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    • v.36 no.2 s.115
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    • pp.91-102
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    • 2006
  • Tooth eruption requires remodeling of surrounding tissues. This study was aimed to investigate the effect of indomethacin on the dental follicle and paradental tissues during tooth eruption by observing the distribution and expression of MMP by the immunohistochemical method. Ten mongrel dogs of ten to twelve weeks old were divided into 5 groups; four experimental groups administered indomethacin 2 mg/Kg/day and 8 mg/Kg/day orally 2 times a day for 14 days and 7 days respectively, and the control group was administered a placebo. Permanent teeth before eruption and their surrounding tissues were selected and excised. H&E staining and immunohistochemical stainings of MMP-3 and -9 were performed and examined under the light microscope. Osteoclasts, osteoblasts, periodontal ligament cells, ameloblasts and odontoblasts of the control group all expressed MMP-3 and -9. In the experimental group, osteoclasts, osteoblasts and periodontal ligament cells showed reduced expression of MMP-3 and -9. Magnitude of MMP reduction In the experimental group showed a time and dose of indomethacin administration dependent manner. These results show that indomethacin inhibited MMP-3 and -9 expression in the dental follicle and surrounding tissues and suggest that when indomethacin is administered for long periods, tooth eruption could be delayed.

Analysis of Single Nucleotide Polymorphism of MMP3 Gene in Korean Genome

  • Kim, Su-Mi;Kim, Su-Won;Yoo, Min
    • Biomedical Science Letters
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    • v.18 no.1
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    • pp.76-78
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    • 2012
  • MMP3 (Matrix metalloproteinase-3) is an important gene in the development of cardiovascular and metabolic diseases. It is also reported that the genotype of MMP3 could be a factor for disease conditions. So, SNP analysis is a prerequisite to study MMP3 related diseases. However, statistical data or analytical reports of this gene in the Korean population is not available. We have employed PCR and ARMS technique to amplify the position of Lys45Glu which is located within chromosome 11q22.3 and exon 2. Genomic DNA were extracted from 201 people. We found that, 17 individuals had the wild homozygote type (W/W, 8%), 98 individuals had the SNP homozygote type (S/S, 49%), 86 had the heterozygote type (W/S, 43%). This study should facilitate research on the cause of cardiovascular diseases due to polymorphisms in the MMP3 gene and to develop further therapy at the genetic level.

Effect of Mulberry Extracts on Secretion of MMPs and Plasmin in U-373-MG Cells (U-373-MG 세포에서 MMPs 및 플라스민의 분비에 미치는 오디 추출물의 효과)

  • Lee, Suk-Hee;Kim, Hwan-Gyu
    • KSBB Journal
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    • v.23 no.2
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    • pp.142-146
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    • 2008
  • In order to sprout and migrate, cells must secrete proteinases which are degrading the surrounding extracellular matrix. In this study, we examined the effect of mulberry extracts and combination of mulberry extracts and VEGF on human malignant glioma U-373-MG cells. Mulberry extracts induced the secretion of matrix metalloproteinase-9 (MMP-9) and suppressed the secretion of MMP-2 and plasmin. Mulberry extracts inhibited the VEGF-induced MMP-2, MMP-9 and plasmin secretion. It is therefore, suggested that mulberry extracts can suppress the VEGF-induced tumor angiogenesis in U-373-MG cells. Also, mulberry extracts induced the secretion of MMP-9 and plasmin through PI 3'-kinase pathway in U-373-MG cells.

Effects of PTTG Down-regulation on Proliferation and Metastasis of the SCL-1 Cutaneous Squamous Cell Carcinoma Cell Line

  • Xia, Yong-Hua;Li, Min;Fu, Dan-Dan;Xu, Su-Ling;Li, Zhan-Guo;Liu, Dong;Tian, Zhong-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6245-6248
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    • 2013
  • Aims: To study effects of down-regulation of pituitary tumor-transforming gene (PTTG) on proliferation and metastasis ability of the SCL-1 cutaneous squamous cell carcinoma (CSCC) cell line and explore related mechanisms. Methods: SCL-1 cells were divided into 3 groups (untreated, siRNA control and PTTG siRNA). Cell proliferation assays were performed using a CCK-8 kit and proliferation and metastasis ability were analyzed using Boyden chambers. In addition, expression of MMP-2 and MMP-9 was detected by r-time qPCR and Western blotting. Results: Down-regulation of PTTG could markedly inhibit cell proliferation in SCL-1 cells, compared to untreated and control siRNA groups (P < 0.05). Real-time qPCR demonstrated that expression levels of PTTG, MMP-2 and MMP-9 in the PTTG siRNA group were 0.8%, 23.2% and 21.3% of untreated levels. Western blotting revealed that expression of PTTG, MMP-2 and MMP-9 proteins in the PTTG siRNA group was obviously down-regulated. The numbers of migrating cells ($51.38{\pm}4.71$) in the PTTG siRNA group was obviously lower than that in untreated group ($131.33{\pm}6.12$) and the control siRNA group ($127.72{\pm}5.20$) (P < 0.05), suggesting that decrease of proliferation and metastasis ability mediated by PTTG knock-down may be closely correlated with down-regulation of MMP-2 and MMP-9 expression. Conclusion: Inhibition of PTTG expression may be a new target for therapy of CSCC.