• Title, Summary, Keyword: MMP-3

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Effects of Extracellular Stimulation of Different Niche Condition on the Transcriptional Regulation of Matrix Metalloproteinase Genes in the Mouse Embryonic Stem Cells

  • Yun, Jung Im;Kim, Min Seong;Lee, Seung Tae
    • Reproductive and Developmental Biology
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    • v.37 no.2
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    • pp.79-83
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    • 2013
  • Matrix metalloproteinases (MMPs) have been known to affect to cell migration, proliferation, morphogenesis and apoptosis by degrading the extracellular matrix. In the previous studies, undifferentiated mouse embryonic stem cells (ESCs) were successfully proliferated inside the extracellular matrix (ECM) analog-conjugated three-dimensional (3D) poly ethylene glycol (PEG)-based hydrogel. However, there is no report about MMP secretion in ESCs, which makes it difficult to understand and explain how ESCs enlarge space and proliferate inside 3D PEG-based hydrogel constructed by crosslinkers containing MMP-specific cleavage peptide sequence. Therefore, we investigated what types of MMPs are released from undifferentiated ESCs and how extracellular signals derived from various niche conditions affect MMP expression of ESCs at the transcriptional level. Results showed that undifferentiated ESCs expressed specifically MMP2 and MMP3 mRNAs. Transcriptional up-regulation of MMP2 was caused by the 3D scaffold, and activation of integrin inside the 3D scaffold upregulated MMP2 mRNAs synergistically. Moreover, mouse embryonic fibroblasts (MEFs) on 2D matrix and 3D scaffold induced upregulation of MMP3 mRNAs, and activation of integrins through conjugation of extracellular matrix (ECM) analogs with 3D scaffold upregulated MMP3 mRNAs synergistically. These results suggest that successful proliferation of ESCs inside the 3D PEG-based hydrogel may be caused by increase of MMP2 and MMP3 expression resulting from 3D scaffold itself as well as activation of integrins inside the 3D PEG-based scaffold.

Parkin Induces MMP-3 Expression in Human Cervical Cancer Cells

  • Lee, Min Ho;Jung, Byung Chul;Jung, Bae Dong;Lee, In-Soo;Rhee, Ki-Jong;Kim, Yoon Suk
    • Biomedical Science Letters
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    • v.19 no.1
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    • pp.1-8
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    • 2013
  • Parkin is known to be a tumor suppressor protein. Previously, we determined that parkin expression restores susceptibility to TNF-${\alpha}$-induced death of HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. MMP-3 is a zinc-dependent protease recently reported to activate intracellular apoptotic signaling. In this study we examined the regulation of MMP-3 expression by parkin in TNF-${\alpha}$-treated HeLa cells. Furthermore, we investigated the signaling pathway involved in parkin-induced expression of MMP-3. We found that HeLa cells exhibit low levels of MMP-3 but is induced after introduction of the parkin gene into HeLa cells. Furthermore, MMP-3 expression increased further when parkin expressing cells were treated with TNF-${\alpha}$. Using chemical inhibitors of cell signaling pathways, we found that MEK-1 (PD98059), PI3K (LY294002), p38 MAPK (SB203580), and JNK inhibitors alleviated parkin-induced up-regulation of MMP-3. Finally, we show that TNF-${\alpha}$-induced cell death in parkin expressing cells is inhibited by using a MMP-3 inhibitor. These results suggest that parkin expression induces prolonged expression of MMP-3 via MEK-1, PI3K, MAPK, and JNK pathway in HeLa cells allowing the HeLa cells to become sensitive to TNF-${\alpha}$-induced cell death. These results implicate a role of MMP-3 in parkin-induced cell death in TNF-${\alpha}$ treated HeLa cells.

Influence of Smoking Cessation on Periodontal Biomarkers in Gingival Crevicular Fluid for 1 Year: A Case Study (1년간 금연이 미치는 치은열구액 내 치주염 바이오마커 변화: 사례연구)

  • Hwang, Soo-Jeong
    • Journal of dental hygiene science
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    • v.14 no.4
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    • pp.525-536
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    • 2014
  • Although tobacco use has been known as one of the biggest risk factors on periodontal health, little is known about the effect of smoking cessation on it. The aim of this study was to investigate the change of concentration of matrix metalloproteinase (MMP)-8, MMP-9 and interleukin (IL)-$1{\beta}$ in gingival crevicular fluid (GCF) of 11 quit-smokers for 1 year after smoking cessation. Eleven male subjects to maintain quit-smoking for 1 year participated the oral examination, GCF and saliva collection without periodontal treatments at baseline, after 2 weeks, 2 months, 4 months, 6 months and 1 year. To confirm quit-smoking, nicotine and cotinine concentrations in saliva were measured by high performance liquid chromatography. MMP-8, MMP-9 and IL-$1{\beta}$ concentrations in GCF of upper anterior teeth area were measured by enzyme-linked immunosorbent assay. Change of MMP-8 in GCF during smoking cessation showed fluctuation with decrease (5 subjects) or increase (2 subjects) or maintenance tendency (4 subjects). Changes of MMP-9 were decrease (6 subjects), or increase (2 subjects), or maintenance (3 subjects). Change of IL-$1{\beta}$ also showed fluctuation with decrease (5 subjects) or increase (3 subjects) or maintenance tendency (3 subjects). The subjects with increase tendency had the relatively smaller amount concentration of MMP-8 and MMP-9 at the baseline. It was unclear smoking cessation without periodontal treatment could affect MMP-8, MMP-9, and IL-$1{\beta}$ in GCF. Fluctuation of periodontal biomarkers during smoking cessation might result from feedback interaction between environmental factors and periodontal cells.

Regulatory mechanism of Angelica Gigas extract powder on matrix metalloproteinases in vitro and in vivo model (참당귀 추출분말이 in vitro and in vivo model에서 MMPs 조절 기전)

  • Kwon, Jin-Hwan;Han, Min-Seok;Lee, Yong-Moon
    • Analytical Science and Technology
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    • v.28 no.6
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    • pp.361-369
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    • 2015
  • The precise mechanism underlying the therapeutic efficacy of an extraction powder of Angelica gigas (AGE) for the treatment of degenerative osteoarthritis was investigated in primary cultured rabbit chondrocytes and in a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. The treatment with AGE (50 μg/mL) effectively inhibited NF-B activation. The anti-inflammatory mechanism was clarified by gelatin zymography and western blotting measurements of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities. The AGE (50 μg/mL) treatment significantly reduced MMP-9 activity. The constituents of AGE— decursinol, decursin, and decursinol angelate—were determined by LC-MS/MS after a 24 hr treatment of rabbit chondrocytes. The contents of the major products, decursin and decursinol angelate, were 3.62±0.47 and 2.14 ±0.36 μg/mg protein, respectively in AGE-treated (50 μg/mL) rabbit chondrocytes. An in vivo animal study on rats fed a diet containing 25, 50, and 100 mg/kg AGE for 3 weeks revealed a significant inhibition of the MMPs in the MIA-induced rat articular cartilage. The genetic expression of arthritic factors in the articular cartilage was examined by RT-PCR of collagen Type I, collagen Type II, aggrecan, and MMP (MMP3, MMP-9, MMP13). Specifically, AGE up-regulated the expression of collagen Type I, collagen Type II, and aggrecan and inhibited MMP levels at all tested concentrations. Collectively, AGE showed a strong specific site of action on MMP regulation and protected against the degeneration of articular cartilage via cellular regulation of MMP expression both in vitro and in vivo.

Inhibitory Activity of Blueberries on UVB-induced Oxidative Stress and Matrix Metalloproteinase Expression in Human Skin Fibroblasts (인간피부 섬유아세포에서 UVB 유도된 산화 스트레스와 기질금속단백질가수분해효소 발현에 블루베리의 저해능)

  • Jang, Young Ah;Kim, Se Gie
    • Journal of Life Science
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    • v.29 no.12
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    • pp.1321-1328
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    • 2019
  • Intermediate-wavelength solar radiation, also known as ultraviolet B (UVB: 290-320 nm) radiation, may cause premature aging and oxidative damage-dependent skin cancer in humans. UVB-induced formation of reactive oxygen species (ROS)-often a consequence of excessive exposure to these rays-could activate matrix metalloproteinases (MMPs) such as MMP-1 and MMP-3. These enzymes break down type I collagen in human fibroblasts. In this study, we assessed the antioxidant and anti-aging effects of ethyl acetate extract of blueberry (EEB). An antioxidant test in blueberries evaluated ROS production using CCD-986sk cells and DPPH assay. In order to evaluate the anti-wrinkle efficacy of blueberries, the MMP-1 production and type 1 procollagen synthesis evaluated and the expression of MMP 1, 3 were tested through Western blot and RT- PCR. EEB exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and reduced the production of UVB-induced ROS. Also, EEB inhibited UVB-induced processes associated with photoaging and skin cancer, such as reduction in procollagen production and increase in MMP-1 production. More precisely, EEB (50 ㎍/ml) markedly suppressed mRNA and protein levels of MMP-1 and -3. The anti-aging effects are attributable to the antioxidant activity of EEB. These findings indicate that EEB has a protective effect against UVB-induced aging in human fibroblast cells by regulating the levels of type-1 procollagen, MMP-1, and MMP-3.

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.

MMP-2, MMP-8 Expression in gingival tissue of Chronic Periodontitis associated to Type 2 Diabetes Mellitus (2형 당뇨병을 동반한 만성 치주염 환자의 치은조직에서 MMP-2, MMP-8의 발현 양상 비교)

  • Kang, Min-Gu;Cha, Hyun-Jeong;Song, Sun-Hee;Park, Jin-Woo;Suh, Jo-Young;Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • v.35 no.3
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    • pp.661-674
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    • 2005
  • The purpose of this study was to quantify and compare the level of MMP-2, MMP-8 in the healthy, inflammed gingival tissue and inflammed gingival tissue associated with type 2 DM. We investigate whether expression of MMP-2, MMP-8 is increased by chronic periodontitis associated with type 2 DM. Gingival tissue samples were obtained during periodontal surgery or tooth extraction. Based on patient's systemic condition & clinical criteria of gingiva, each gingival samples were divided into three groups. Group l(n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from 8 systemically healthy patients. Group 2(n=8) is inflammed gingiva from patients with chronic periodontitis. Group 3(n=8) is inflammed gingiva from type 2 diabetic patients with chronic periodontitis. Tissue samples were prepared and analyzed by Western blotting. The quantification of MMP-2, MMP-8 was performed using a densitometer and statistically analyzed by ANOVA. MMP-2, MMP-8 was expressed in all samples including healthy gingiva and increased in group 3 compared to group 1 and 2, and showed that significant variation was observed between group 1 & 3 in MMP-8 results. In conclusion, this study demonstrated that human gingival tissue with chronic periodontitis associated to type 2 diabetes showed slightly elevated MMP-2, MMP-8 levels compared to healthy gingiva and non-diabetic inflamed gingiva.

Evaluation of Effective MMP Inhibitors from Eight Different Brown Algae in Human Fibrosarcoma HT1080 Cells

  • Bae, Min Joo;Karadeniz, Fatih;Ahn, Byul-Nim;Kong, Chang-Suk
    • Preventive Nutrition and Food Science
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    • v.20 no.3
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    • pp.153-161
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    • 2015
  • Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that have important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Marine plants are on the rise for their potential to provide natural products that exhibit remarkable health benefits. In this context, brown algae species have been of much interest in the pharmaceutical field with reported instances of isolation of bioactive compounds against tumor growth and MMP activity. In this study, eight different brown algae species were harvested, and their extracts were compared in regard to their anti-MMP effects. According to gelatin zymography results, Ecklonia cava, Ecklonia bicyclis, and Ishige okamurae showed higher inhibitory effects than the other samples on MMP-2 and -9 activity at the concentrations of 10, 50, and $100{\mu}g/mL$. However, only I. okamurae was able to regulate the MMP activity through the expression of MMP and tissue inhibitor of MMP observed by mRNA levels. Overall, brown algae species showed to be good sources for anti-MMP agents, while I. okamurae needs to be further studied for its potential to yield pharmaceutical molecules that can regulate MMP-activity through cellular pathways as well as enzymatic inhibition.

Simvastatin as a Modulator of Tissue Remodeling through Inhibition of Matrix Metalloproteinase (MMP) Release from Human Lung Fibroblasts

  • Ra, Ji-Eun;Lee, Ji-Kyoung;Kim, Hui-Jung
    • Tuberculosis and Respiratory Diseases
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    • v.71 no.3
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    • pp.172-179
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    • 2011
  • Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-${\alpha}$, TNF-a and interleukin-$1{\beta}$, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.

The Effect of Matrix Metalloproteinase Inhibitor for Left Ventricular Remodeling after Myocardial Infarction in a Rabbit Model (토끼에서 Myocardial Infarction 후 Left Ventricular Remodeling에 대한 Matrix Metalloproteinase의 차단 효과)

  • Kim, Soo-Hyun;Jung, Tae-Eun;Hong, Geu-Ru;Han, Sung-Sae
    • The Korean Journal of Thoracic and Cardiovascular Surgery
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    • v.40 no.5
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    • pp.329-340
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    • 2007
  • Background: Matrix Metalloproteinase (MMP) inhibition has emerged as a potential therapeutic strategy for the left ventricular dilatation that occurs after myocardial infarction. This study is designed to evaluate which treatment is better for attenuating the left ventricular remodeling via MMP inhibition 1) during the early, short highly MMP producing period of the initial phase or 2) during most of the period of the initial phase after myocardial infarction. Material and Method: Myocardial infarction was induced by ligation of the left anterior descending coronary artery in rabbits. The experimental group was divided into 3 groups. The myocardial infarction only (MI only) group consisted of 7 cases. The MMP inhibitor administered for 5 days after MI (MMPI 50) group had 6 cases, and these rabbits were given MMP inhibitor for 5 days after myocardial infarction, beginning with the postoperative first day. MMP inhibitor administered for 9 days (MMPI 90) group consisted of 5 cases and these rabbits were given MMPI for 9 days the same manner as above. CG2300 was used as a selective MMPI; this is a potent MMP-2 and -9 inhibitor Two-D echocardiograms were performed on all the groups at the time of preoperative period, the post-operative 1st week, the postoperative 20 week and the postoperative 30 week, and we measured the end-diastolic dimension (EDD), the end-systolic dimension (ESD), and the ejection fraction (EF). Result: The echocardiograms generally showed postoperative left ventricular dilatation in the MI only group. The EDD was increased significantly higher in the postoperative 1 week compared to the preoperative value (p<0.05). The ESD was also increased significantly higher in the postoperative 1st week, the postoperative 20 week and the postoperative 30 week compared to the preoperative value (p<0.05). Left ventricular dilatation was noted to be less In the MMPI 9d group than in the MI only and MMPI 5d groups. In the MMPI 9d group, there was no significant change of EF postoperatively compared to the preoperative period. MMP-2 and MMP-9 were measured from the infarcted myocardial tissue at post-MI 4 weeks by performing western blotting and zymography. The changes the of protein expression and activity of MMP-2 and MMP-9 were not significant in the three MI groups and the normal heart group. Histopathologic examination revealed severe collagen deposition in the MI only group. Collagen accumulation was reduced in both the MMPI groups. The MMPI 9d group revealed an increased number of capillaries. Conclusion: Left ventricular dilatation developed rapidly after, MI from ligation of the coronary artery and MMPI attenuated the ventricular dilatation. The effect of MMPI seemed to have better a result from its usage during most of the period of the initial phase after myocardial infarction. This suggested that increased neovascularization by MMPI may also contribute to attenuation of the left ventricular remodeling.