• Journal of dental hygiene science
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• v.12 no.1
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• pp.71-77
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• 2012

Sex Hormones exert significant influence in body physiology throughout life. Some reports suggested increased sex hormone levels correlate with an increased prevalence of gingivitis. The objectives of this pilot study are to(1) address the link between menstrual cycle and MMP-9, MMP-8, IL-$1{\beta}$ of gingival crevicular fluid during 4 weeks and (2) discuss the major biomarker of periodontal status. 7 female and 3 male volunteer who didn't have smoking habit, medical and dental disease after informed consent, were seen twice a week for 4 weeks. GCF samples were collected and GCF levels of MMP-9, MMP-8, IL-$1{\beta}$ were measured by enzyme-linked immunosorbent assay. The GCF levels of MMP-9, MMP-8, IL-$1{\beta}$ had fluctuation according to menstrual cycle, but the changes of those were not significant by Friedman matched samples test. There is no difference between female and male subjects by Mann-Whitney U test. The correlation of MMP-8, MMP-9 and IL-$1{\beta}$ showed strong by Spearman correlation(0.644-0.945). This study confirms menstrual cycle doesn't influence the periodontium of healthy female subjects.

• Journal of Embryo Transfer
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• v.29 no.2
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• pp.101-109
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• 2014

Matrix Metalloproteinases (MMP)-2 and -9 are participated in embryo development, implantation, remodeling of epithelial cell and ovulation. The objective of this study is to evaluate an impact of MMP2 and MMP9 on embryonic developmental competence as well as gene expression profiles of in vitro-produced bovine embryos. After in vitro fertilization, embryos of all groups were transferred into IVC-2 medium treated with MMP2 and MMP9 to check the optimum concentration on the basis of embryo development competence and cell numbers. The optimum concentrations for MMP2 and 9 were 1,200 ng/ml and 300 ng/ml. The blastocyst development competence was not different among 1,200 ng/ml of MMP2 vs. 300 ng/ml of MMP9 vs. combined MMP2 + 9 vs. control groups ($41.46{\pm}10.66$ vs. $37.73{\pm}8.92$ vs. $45.11{\pm}11.41%$ vs. $41.59{\pm}11.88$, respectively). Furthermore, the developmental competences to hatching and hatched blastocysts were not also different among the same groups ($79.84{\pm}12.63$ vs. $83.3{\pm}17.46$ vs. $78.55{\pm}14.48%$ vs. $72.02{\pm}14.09$). In addition, total cell number was significantly (p<0.05) greater in blastocyst treated with MMP9 300 ng/ml among all treatment groups. On the other hand, there was no significant difference of ICM vs. TE ratio in all groups. The expression of five out of six genes (i.e., MMP2, MMP9, IFNt, SSLP1 and HNRNPA2B1) was different among the groups. The expression of IFNt and HNRNPA2B1 genes was significantly greater in MMP9 (p<0.05), but there was no difference of MMP9 expression between MMP2 and MMP9 group (p>0.05). The normalized expression of MMP2 and SSLP1 was greater in MMP2 than other groups (p<0.05). In conclusion, MMPs treatment during IVC-2 medium was remarkably effected on blastocyst developmental competence and gene expression profiles that are related to embryo quality and implantation.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.197-204
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• 2017

In the present study, we tried to examine whether oleanolic acid regulates the activity, secretion and gene expression of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as the production of MMP-3 in the knee joint of rat to evaluate the potential chondroprotective effect of oleanolic acid. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-$1{\beta}$ (IL-$1{\beta}$)-induced gene expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen. In rabbit articular chondrocytes, the effects of oleanolic acid on IL-$1{\beta}$-induced secretion and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of oleanolic acid on in vivo MMP-3 protein production was also examined, after intra-articular injection to the knee joint of rat. The results were as follows: (1) oleanolic acid inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5, but increased the gene expression of type II collagen; (2) oleanolic acid reduced the secretion and proteolytic activity of MMP-3; (3) oleanolic acid suppressed the production of MMP-3 protein in vivo. These results suggest that oleanolic acid can regulate the activity, secretion and gene expression of MMP-3, by directly acting on articular chondrocytes.

• Korean Journal of Head & Neck Oncology
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• v.18 no.2
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• pp.135-141
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• 2002

Backgrounds and Objectives: Metastasis is a complex multistep process that requires sequential interactions between the invasive cell and the extra-cellular matrix. Transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) is a multifunctional regulator of cellular differentiation, motility and growth. Loss of sensitivity to the growth inhibitory effects by $TGF-{\beta}1$ plays important roles in neoplastic progression. The aim of this study was to investigate the role of $TGF-{\beta}1$ in the neoplastic invasion and metastasis through matrix metalloproteinase (MMP) of laryngeal cancer cell lines. Material and Methods: Two laryngeal cancer cell lines, SNU-899 and SNU-1076 were treated with recombinant $TGF-{\beta}1$, and the expression of MMP-2 and MMP-9 was immunohistochemically evaluated and gelatinase activity was studied by gelatin zymogram. Results: The cell growth inhibition was evident on 4th days after 1ng/ml and 10ng/ml $TGF-{\beta}1$ treatment. The expressions of MMP-2 and MMP-9, and their gelatinase activities were increased in dose-dependent manner. Conclusion: $TGF-{\beta}1$ treatment in laryngeal cancer cell lines induces the expression of MMP-2 and MMP-9, thus playing a role in the digestion of extracellular matrix gelatin.

• KSBB Journal
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• v.25 no.3
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• pp.265-270
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• 2010

Simvastatins are widely used to reduce endogenous cholesterol synthesis and improve hypercholesterolemia. Also, simvastatin have been shown to induce both angiogenic and angiostatic responses. In this study, It was attempted to resolve this controversy by studying the effects of simvastatin on the cell migration and invasion with the proteinases secretion and expression pattern. U-373-MG cells treated with low dose of simvastatin ($0.001{\sim}0.5\;{\mu}M$) showed the induction of migration and invasion compared with the addition of a control buffer. On the contrary, high dose of simvastatin ($1{\sim}20\;{\mu}M$) showed the reduction of migration and invasion compared with the addition of a control buffer. It was also showed that simvastatin-regulated migrative and invasive phenotypes were consistent with the secretion and expression pattern of matrix metalloproteinase-2 (MMP-2), MMP-9 and plasmin.

• Journal of Life Science
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• v.26 no.5
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• pp.614-619
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• 2016

The prostate-apoptosis-response-gene-4 (Par-4) protein has been identified as an effector of cell death in response to various apoptotic stimuli in prostate cancer cells. We found that overexpression of Par-4 by stable transfection inhibits cell migration and invasion in Caki cells. The expression of various matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we investigated whether ectopic expression of Par-4 modulates MMP-2 expression and activity in human renal carcinoma Caki cells. We found that overexpression of Par-4 markedly inhibited MMP-2 activity, but not MMP-9 activity. However, loss of the leucine zipper domain of Par-4 (Par-4 ΔLZ#1 and #2) did not inhibit MMP-2 activity. Further, knock-down of Par-4 with the corresponding siRNA resulted in increased invasion and metastasis of renal carcinoma Caki cells. Interestingly, overexpression or knock-down of Par-4 did not affect the expression levels of MMP-2 mRNA. Taken together, our findings suggest that Par-4 may inhibit MMP-2 activity through its post-transcriptional regulation in renal carcinoma Caki cells.

• BMB Reports
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• v.32 no.1
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• pp.60-66
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• 1999

Matrix metalloproteinase-2 (MMP-2; 72-kDa gelatinase; 72-kDa type IV collagenase; gelatinase A) plays an important role in normal physiological processes and in many pathologic processes such as arthritis and metastasis of cancer. Tissue inhibitor of metalloproteinases-2 (TIMP-2) binds to proMMP-2 or mature MMP-2 at a 1:1 ratio and inhibits the catalytic activity of MMP-2. We demonstrated that the baculovirus/insect cell system does not have TIMP-2 activity. The human proMMP-2 free of TIMP-2 was expressed in the expression system and purified by one-step affinity chromatography using gelatin-Sepharose. The free proMMP-2 was autoactivated to the mature MMP-2 and autodegraded into smaller molecular weight forms in the absence of external activator. The activation and autodegradation of the proMMP-2 was much more rapid in the presence of 4-aminophenylmercuric acetate (APMA). Addition of TIMP-2 inhibits both APMA-induced activation and autodegradation of the free proMMP-2. However, an increasing concentration of TIMP-2 more readily inhibited activation of the free proMMP-2 than autodegradation. These results demonstrate that TIMP-2 plays roles in inhibition of both activation and autodegradation of the free proMMP-2 in addition to inhibition of the catalytic activity of MMP-2.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.163-170
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• 2016

We examined whether apigenin affects the gene expression, secretion and activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as in vivo production of MMP-3 in the knee joint of rat to evaluate the potential chondroprotective effects of apigenin. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription - polymerase chain reaction (RT-PCR) was used to measure interleukin-$1{\beta}$ (IL-$1{\beta}$)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and ADAMTS-5. In rabbit articular chondrocytes, the effects of apigenin on IL-$1{\beta}$-induced secretion and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of apigenin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, apigenin inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. Furthermore, apigenin inhibited the secretion and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that apigenin can regulate the gene expression, secretion, and activity of MMP-3, by directly acting on articular chondrocytes.

• 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.

• Fisheries and Aquatic Sciences
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• v.21 no.6
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• pp.16.1-16.7
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• 2018

Background: Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content. Methods: In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells. S. horneri crude extract was fractionated with organic solvents, namely, water ($H_2O$), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solvent-partitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting. Results: All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography. Except $H_2O$ fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Conclusion: Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules.