• Title/Summary/Keyword: Matrix Metalloproteinase(MMP)

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Study on the Expression of Matrix Metalloproteinase-1 by Promoter Polymorphism in Human Dermal Fibroblast (섬유아세포에서 프로모터 다형성에 의한 Matrix Metalloproteinase-1의 발현에 관한 연구)

  • Lee, Jin Woo;Jung, Yujung;Bong, Sim-Kyu;Park, No-June;Lee, Sang Heon;Noh, Minsoo;Lim, Kyung-Min;Kim, Su-Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.47 no.3
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    • pp.205-212
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    • 2021
  • The skin fibroblasts of different origins showed different expression levels of MMP-1 in response to TNF-α treatment or UV irradiation. We hypothesized that this is caused by polymorphism in the MMP-1 promoter region. To elucidate it, first of all, we analyzed and classified the genotype of the -1607 site of the MMP-1 promoter in 23 commercially available primary fibroblasts, and then we examined the expression of MMP-1 by TNF-α or UVB stimulation for each classified genotype. As a result of the analysis, fibroblasts with 6 1G/1G genotypes, 10 1G/2G genotypes, and 7 2G/2G genotypes were identified. Hs68 and Detroit 551 cell lines were confirmed to have 1G/2G genotypes. In the 1G/1G genotype, MMP-1 was expressed twice as high as that of the control group by TNF-α treatment, and was hardly expressed by UV light. In the case of the 1G/2G genotype, MMP-1 was expressed 2.45 fold higher by TNF-α treatment, and 1.4 fold by UV light than the control. In the case of the 2G/2G genotype, MMP-1 was expressed 1.35 fold by TNF-α treatment, and was highly expressed by 2.5 fold by ultraviolet rays compared to control. It can be estimated that MMP-1 expression is better induced in the 1G genotype by TNF-α and in the 2G genotype by UV light. In addition, it can be presumed that MMP-1 expression is increased by creating a site where the Ets transcription factor can bind by another G inserted at the -1607 position. These studies have not been conducted at all in fibroblasts in relation to skin aging, so it is an area that needs to be further studied in the future. In conclusion, since the skin is an organ that is affected by both intrinsic aging and photoaging at the same time, when analyzing the expression of MMP-1 as a target for improving skin aging, it is necessary to select cells with a genotype suitable for the experimental conditions of the study.

Clinical Study of Tumor Angiogenesis and Perfusion Imaging Using Multi-slice Spiral Computed Tomography for Breast Cancer

  • Xu, Na;Lei, Zhen;Li, Xiao-Long;Zhang, Jun;Li, Chen;Feng, Guo-Quan;Li, Di-Nuo;Liu, Jing-Yi;Wei, Qiang;Bian, Ting-Ting;Zou, Tian-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.429-433
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    • 2013
  • Objectives: To explore the correlation between multi-slice spiral CT (MSCT) perfusion parameters and the expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-2 (MMP-2) in breast cancer. Methods: Forty five breast cancer patients and 16 patients with benign breast tumor, both confirmed by pathology examination, were enrolled. All underwent MSCT perfusion imaging to obtain perfusion maps and data for parameters including blood flow (BF), blood volume (BV) and permeability surface (PS). Cancer patients did not receive treatment prior to surgery. The expression of VEGF and MMP-2 were examined with both immunohistochemistry and Western blotting. Results: The levels of VEGF and MMP-2 by immunohistochemistry were significantly higher in the breast cancer group (P < 0.01) than the benign tumor group. Relative OD values from Western blotting were also higher in cancer cases (P < 0.05). Similarly, the mean MSCT perfusion parameters (BF, BV, PS) were significantly higher in the breast cancer group (P < 0.01), BF and BV positively correlating with VEGF expression (r = 0.878 and 0.809 respectively, P < 0.01); PS and VEGF and MMP-2 expression were also positively correlated (r= 0.860, 0.786 respectively, P < 0.01). Conclusion: There is a correlation between breast cancer MSCT perfusion parameters and VEGF andMMP-2 expression, which might be useful for detection of breast lesions, qualitative diagnosis of breast cancer, and evaluation of breast cancer treatment.

Protective effect of Thymus quinquecostatus extracts UVB-induced matrix metalloproteinase-1 via suppressing MAPKs phosphorylation in human keratinocyte (사람의 각질세포에서 UVB 유도에 따른 MMP-1의 발현 조절과 MAPKs 인산화에 타임 추출물이 미치는 효과)

  • Jung, Hana;Jeong, Hyun Ju;Shin, Kyounghee;Kim, Yung Sun;Moon, Jae Heon;Lee, Tae Hoon
    • Journal of Applied Biological Chemistry
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    • v.61 no.4
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    • pp.417-421
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    • 2018
  • Ultraviolet rays are electromagnetic waves with a shorter wavelength than visible light, and ultraviolet rays that pass through the ozone layer are the main cause of skin aging. Chronic exposure of skin tissue to ultraviolet light activates the Mitogen-activated Protein Kinases (MAPKs) signaling pathways in human keratinocytes, resulting in increased production of matrix metalloproteinases (MMPs). In this study, we investigated the herbal extracts from Jeju Island on the anti-aging effect in human keratinocytes (HaCaTs) by ultraviolet stimulation. We examined that herb extract from Jeju Island were decreased in anti-aging activity on measuring the level of MMP-1 gene and protein expression in ultraviolet-induced keratinocytes. As a result, it was confirmed that Thymus quinquecostatus extract (TQE) significantly reduced the expression of MMP-1 in a dose-dependent manner by UV irradiated HaCaTs. According to our data, TQE significantly attenuated UV-induced phosphorylation of the MAPKs signaling elements ERK1/2, JNK1/2 and p38 proteins. These results suggest that the MAPKs pathway may contribute to the inhibitory effect of TQE on UV-induced MMP-1 production in human keratinocytes. Our results suggest that TQE may be a protective agent against skin aging by preventing UV-induced MMP-1 production.

Anticancer Effects of Cisplatin in Combination with Paeonia Japonica in YD-10B Cells (YD-10B에서 Cisplatin과 백작약의 병용처리에 의한 항암 효과)

  • Kim, Eun-Jung
    • The Journal of the Korea Contents Association
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    • v.20 no.6
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    • pp.124-130
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    • 2020
  • The present study investigated the anti-proliferate and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities of combined treatment with cisplatin and ethyl acetate fractions of Paeonia japonica. Cell Proliferation was detected by the MTS assay and the activity and mRNA expression of MMP-2/-9 were examined by zymography and RT-PCR. As results, cisplatin or p. japonica treatment of YD-10B cells resulted in a dose-dependent inhibition of cell growth. Also, the viability of YD-10B cells treated with combination of 200 μM cisplatin and 50 ㎍/ml p. japonica was inhibited to 50% in compared with the cisplatin alone. In PMA-treated YD-10B cells, co-treatment of 200 μM cisplatin with 50 ㎍/ml p. japonica significantly inhibited mRNA expression and protein activation of MMP-2/-9. Therefore, This study suggest that the combination treatment of cisplatin and p. japonica potentiates a promising anti-invasive agent and has more potential anti-cancer drug for oral cancer therapy than cisplatin alone.

Associations between Single Nucleotide Polymorphisms of COX-2 and MMP-2 Genes and Colorectal Cancer Susceptibility in the Saudi Population

  • Shalaby, Manal Ali;Nounou, Howaida Attia;Alanazi, Mohammad Saud;Alharby, Othman;Azzam, Nahla;Saeed, Hesham Mahmoud
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4989-4994
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    • 2014
  • Background: It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. Materials and Methods: This research evaluated risk of association of the SNPs, including genes for COX-2 (AIG transition at +202) and MMP-2 (Crr transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. Results and Conclusions: Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=O.0121. On the other hand in our study, there was no significant association between genotype distribution ofthe COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency ofthe mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions ofCOX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.

Effect of Antioxidation and Inhibition of Matrix Metalloproteinase-1 from Ligularia fischeri (곰취의 항산화와 UVA에 의한 MMP-1 발현 저해효과)

  • Na, Young;Kim, Jin-Hwa;Sim, Gwan-Sub;Lee, Bum-Chun;Pyo, Hyeong-Bae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.3 s.58
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    • pp.129-134
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    • 2006
  • In this study, we examined the effects of antioxidant, lipid peroxidation inhibition and suppression of UVA-induced MMP-1 expression in human dermal fibroblasts. Ligularia fischeri extract showed free radical scavenging effect by 82.3% at 5 mg/mL and superoxide radical scavenging effect by 79.3% at 5 mg/mL in the kanthine/xanthine oxidase system, respectively. At the concentration of $500{\mu}g/mL$, L. fischeri extract showed 97% inhibition on lipid peroxidation of linoleic acid. UVA induced MMP expression in human dermal fibroblasts was reduced 35% by treatment with $100{\mu}g/mL$ of L. fischeri extract. These results suggest that L. fischeri extract can be used for an anti-aging agent by antioxidation, lipid peroxidation inhibition and reducing UVA-induced MMP-1 production.

Anti-photoaging Constituents from Eurya emarginata Leaves

  • Sung Chun Kim;So Yeon Oh;Hyejin Hyeon;Boram Go;Seon-A Yoon;Yong-Hwan Jung;Nam Ho Lee;Young-Min Ham
    • Journal of the Korean Chemical Society
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    • v.67 no.2
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    • pp.150-155
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    • 2023
  • Eurya emarginata is an evergreen tree growing in the southern regions of Korea including Jeju Island. In this study, antioxidant and anti-photoaging effects were investigated with the extracts of E. emarginata leaves. As comparative studies with the extract and five solvent fractions, the EtOAc fraction showed the most effective DPPH and ABTS+ radical scavenging activities. The EtOAc fraction also inhibited matrix metalloproteinase-1 (MMP-1) production most effectively. Phytochemical study on the EtOAC fraction resulted in the isolation of three compounds; eutigoside C (1), eutigoside B (2) and quercitrin (3). Among the isolates (1-3), quercitrin (3) showed excellent antioxidant activities and inhibitory properties on MMP-1 production. Based on these results, it was suggested that extracts of E. emarginata leaves could be developed as natural anti-photoaging agents in cosmetic formulations.

β3GnT8 Regulates Laryngeal Carcinoma Cell Proliferation Via Targeting MMPs/TIMPs and TGF-β1

  • Hua, Dong;Qin, Fang;Shen, Li;Jiang, Zhi;Zou, Shi-Tao;Xu, Lan;Cheng, Zhi-Hong;Wu, Shi-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2087-2093
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    • 2012
  • Previous evidence showed ${\beta}1$, 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of ${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in ${\beta}3GnT8$. Here we showed that cell proliferation was increased in ${\beta}3GnT8$ overexpressed cells but decreased in ${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in ${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of ${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$), whereas ${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of ${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the ${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma.

Antiangiogenic Effect of 3--O-D-galactopyranosylglyceride Isolated from Chrysanthemum Coronarium L. (개채에서 분리한 3-O--D-galactopyranosylglyceride의 혈관형성 저해효과)

  • Lee Hyun Cheol;Song Ho Chul;Lim Jin Ki;Khil Jae Ho;Kim Sung Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1602-1607
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    • 2004
  • 3-O-D-galactopyranosylglyceride (GPG; fatty acids R1, R2 = myristic acid 11.62%, palmitic acid 61.90% and oleic acid 26.48%) was isolated from Chrysanthemum coronarium L that has been used for treating renal and cardiovascular diseases as one of vegetables or medicinal drug. However, little was known about the anti-angiogenic activity of GPG. Thus, anti-angiogenic effect of GPG was evaluated in human umbilical vein endothelial cells (HUVECs) in vitro and in vivo. GPG effectively inhibited bFGF-induced migration and invasion of HUVECs in a concentration-dependent manner, whereas it did not inhibit bFGF-induced proliferation and capillary-like tube formation of HUVECs. To examine the mechanism of anti-angiogenic activity of GPG, gelatin zymography was carried out. GPG downregulated the expression of matrix metalloproteinase-2 in a concentration-dependent manner. Furthermore, GPG significantly disrupted bFGF-induced neovascularization on the chick chorioallantoic membrane assay in vivo. These results suggest that 3-O--D-galactopyranosylglyceride may inhibit neovascularization by inhibiting angiogenic activity of endothelial cells via regulation of matrix metalloproteinase-2 (MMP-2).

Resveratrol inhibits the protein expression of transcription factors related adipocyte differentiation and the activity of matrix metalloproteinase in mouse fibroblast 3T3-L1 preadipocytes

  • Kang, Nam E;Ha, Ae Wha;Kim, Ji Young;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • v.6 no.6
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    • pp.499-504
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    • 2012
  • This study attempted to investigate the effects of resveratrol on the differentiation of adipocytes. After cells were treated with various concentrations of resveratrol (0, 10, 20, and 40 ${\mu}mol/L$), adipocyte proliferation, the protein expression of transcription factors, and MMPs' activities were determined. Cell proliferation was inhibited more within 4 days of incubation (P<0.05), and lipid accumulation in adipocyte was significantly inhibited by 93.8%, 92.4% and 91.5%, respectively, after two days of 10, 20, and 40 ${\mu}mol/L$ resveratrol treatment (P<0.05). Six days of incubation with the three resveratrol concentrations caused a significantly decreases of 63%, 59.9%, and 25.1% GPDH activity as a dose-dependent response. The triglyceride concentration also decreased significantly with the increase of resveratrol concentration (P<0.05). The protein expression of CCAAT/enhancer-binding protein (C/$EBP{\beta}$) was decreased significantly by 56% and 30% while $PPAR{\gamma}$ was significantly reduced by 57% and 15% with resveratrol treatments of 20 and 40 ${\mu}mol/L$, respectively (P<0.05). The protein expression of C/$EBP{\alpha}$ was decreased by 83%, 74%, and 38% to increased dosage levels, with significance determined for this decrease from 20 ${\mu}mol/L$ of resveratrol. The protein expression of fatty acid binding protein (FABP4) was decreased significantly by 88%, 72%, and 46% with the increase of resveratrol concentration. The activity of MMP-2 was decreased significantly by 84%, 70%, and 63% while MMP-9 activity was decreased significantly by 74%, 62%, and 39% with the increased resveratrol concentrations of 10, 20, and 40 ${\mu}mol/L$, respectively (P<0.05).