• Title/Summary/Keyword: MMP-2/9

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Influence of Smoking on Matrix Metalloproteinase-9 in the Gingival Crevicular Fluid (흡연이 치은열구액 내 Matrix Metalloproteinase-9에 미치는 영향)

  • Hwang, Soo-Jeong;Kim, Young-Kwon;Yang, Seong-Ju;Cho, Hyun-Jeong
    • Journal of dental hygiene science
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    • v.11 no.4
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    • pp.339-344
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    • 2011
  • Matrix metalloproteinase(MMP)-9 is considered important in tissue destruction in periodontitis. The aim of this study was to investigate the influence of smoking on MMP-9 in the gingival crevicular fluid(GCF). GCF samples in upper incisors area from 332 male subjects were collected after the informed consent. The dental examination included the assessment of oral hygiene, gingival inflammation and probing pocket depth. A quantitative assessment of MMP-9 levels in GCF was performed utilizing and immunological procedure. The mean MMP-9 concentrations found in GCF of smokers(30.86 ng/ml) and quit-smokers(29.82 ng/ml) differed from non-smokers(11.33 ng/ml), adjusted by age, gingival index and Community periodontal index(p<0.001). Smoking seems to influence MMP-9 in GCF regardless of gingival inflammation and age. It means smoking can destruct the periodontal tissue for itself.

Matrix metalloproteinases: expression and regulation in the endometrium during the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs

  • Inkyu Yoo;Soohyung Lee;Yugyeong Cheon;Hakhyun Ka
    • Animal Bioscience
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    • v.36 no.8
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    • pp.1167-1179
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    • 2023
  • Objective: Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Results: Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. Conclusion: These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.

Effect of Simvastatin on the Migration and Invasion of U-373-MG Cells (U-373-MG 세포의 이동 및 침윤에 미치는 simvastatin의 효과)

  • Kim, Hwan-Gyu
    • 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.

Anti-wrinkle effect of berberine by inhibition of MMP-2 and MMP-9 activity in fibroblasts (섬유아세포에서의 MMP-2 및 MMP-9 활성 억제에 의한 베르베린의 항주름 효과)

  • Jang, Young-Ah;Lee, Jin-Tae
    • Journal of Applied Biological Chemistry
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    • v.61 no.1
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    • pp.9-15
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    • 2018
  • We analyzed the antioxidant and anti-wrinkle activities of berberine, isolated from dried rhizome of Coptis japonica Makino, to determine its cosmetic potential. We performed the 3-[4,5-dimethylthiazol]-2-yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay to evaluate the toxicity of the berberine. We also measured the ROS and hyaluronic acid production, and expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and tumor necrosis factor-alpha ($TNF-{\alpha}$) to evaluate the antioxidant and anti-wrinkle activities of berberine, respectively. The cytotoxicity of ultraviolet light, in presence of berberine, was measured by the MTT assay using CCD-986sk fibroblasts, and no cytotoxicity was observed at concentrations less than $25{\mu}g/mL$. We also found that berberine decreased ROS production in a concentration-dependent manner and promoted the synthesis of hyaluronic acid. Further, berberine reduced the protein levels and mRNA expression of MMP-2 and MMP-9, which are associated with wrinkle formation, and increased the expression of TIMP-1 and TIMP-2. In addition, the inhibitory effect of berberine on $TNF-{\alpha}$, known as pro-inflammatory cytokine, was inhibited by $TNF-{\alpha}$ gene in a concentration-dependent manner. These results suggest that berberine holds cosmetic value owing to its antioxidant activity, by inhibiting ROS production and anti-wrinkle activity by reducing MMP-2 and MMP-9 and increasing TIMP-1 and TIMP-2 expression.

Anti-invasion Effects of Calystegia soldanella Solvent Extracts and Partitioned Fractions on PMA-stimulated Fibrosarcoma Cells (갯메꽃 추출물과 유기용매 분획물의 암전이 억제 효과)

  • Son, Jaemin;Kim, Junse;Kim, Hojun;Seo, Youngwan
    • Journal of Life Science
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    • v.29 no.3
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    • pp.287-294
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    • 2019
  • Calystegia soldanella is distributed in coastal sand dunes and has high environmental adaptability; it is also known to be effective for anti-oxidant, anti-pyretic, anti-septic, and diuretic action. This study investigated the effect of crude extracts and organic solvent fractions of C. soldanella on MMP-2 and MMP-9 expression, MMP activity, and cell mobility in phorbol-12-myristate-13-acetate (PMA)-induced fibrosarcoma HT-1080 cells. C. soldanella was twice extracted, once with methylene chloride (MC) and once with methanol (MeOH). After the MC and MeOH extracts were combined, their suppressive effects on MMP-2 and MMP-9 expression, MMP enzymatic activity, and gene and protein expression were measured by gelatin zymography, enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction, and western blot method. Cell mobility for the HT-1080 cells was observed by wound healing assay. The combined crude extracts showed a significant suppressive effects on MMP-2 and MMP-9 expression. To explore active inhibitory elements, the combined extracts were fractionated according to polarity into with n-hexane, 85% aqueous methanol, n-butanol, and water. Across these four solvent fractions, MMP-2 and MMP-9 activity and cell mobility in the HT-1080 cells were all strongly inhibited by the n-hexane fraction. These results suggest that C. soldanella extract and organic solvent fractions could be used as potent MMP inhibitors for effective anti-cancer treatments to suppress cancer invasion and metastasis.

Ginsenoside $Rh_1$$Rh_2$의 HT1080 세포 침윤억제 작용에 관한 연구

  • 박문택;차희재
    • Journal of Ginseng Research
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    • v.22 no.3
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    • pp.216-221
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    • 1998
  • We examined the anti-invasive activity of ginsenosides Rhl, Rha on the highly metastatic HT1080 human fibrosarcoma cell line. In vitro invasion assay showed ginsenoside Rhr reduced tumor cell invasion through a reconstituted basement membrane in a transwell chamber more than ginsenoside Rh1. Significant down-regulation of matrix metalloproteinase-9 (MMP-9) by ginsenosides Rh, and Rh2 was detected by Northern blot analysis. However, the expression of MMP-2 was not affected by Rh, and Rhr. The expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by Rhl after 0.5, 1 or 3 day-treatment but reduced after 6 day-treatment. However, the expression of TIMP-2 was not changed by treatment with Rh2. Plasminogen activator inhibitor (PAI) and urokinase-type plasmlnogen activator (uPA) were not changed by treatment with Rh1 and Rh2 for 3 and 6 days. Quantitative gelatin-based zymography confirmed a markedly reduced expression of MMP-9 but MMP-2 after treatments with ginsenosides Rhl and Rha. These results suggest that down-regulation of MMP-9 contributes to the anti-invasive activity of ginsenosides Rhl and Rhr in the HT1080 cells.

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Inhibitory Effects of Type IV Collagenase by Disulfiram (Disulfiram에 의한 type IV collagenase 저해효과)

  • Sin, Doo-Il;Park, Jae-Bok;Park, Kwan-Kyu;Cho, Chang-Ho;Oh, Hoon-Kyu;Choi, Chang-Hyuk;Cho, Hyun-Ji;Chang, Young-Chae
    • Journal of Life Science
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    • v.16 no.6
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    • pp.964-971
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    • 2006
  • The cancer cells, characterized by local invasion and distant metastasis, are very dependant on extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Among the human MMPs, matirx metalloproteinase-2 (MMP-2) and matrix metalloproteinse-9 (MMP-9) are key enzymes that degrade type IV collagen of the matrix. Here, we studied the effect of disulfiram, an anti-tumor compound, on the suppression of the tumor invasion and the activity of MMP-2, MMP-9 in human osteosarcoma cells (U2OS). Disulfiram had the type IV collagenase inhibitory activity, the effect of inhibition of gene and protein expression, and these inhibitions were responsible for blocking invasion through cell mediated and non-cell mediated pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9, and regulated the invasion of U2OS, Caki-1 and Caski. These observations raise the possibility of clinical therapeutic applications for disulfiram used as a potential inhibitor of cancer invasion.

Production of PMA-induced MMP-2 and MMP-9 in the HT-1080 Fibrosarcoma Cell Line is Inhibited by Corydalis heterocarpa via the MAPK-related Pathway (PMA로 자극된 HT-1080 세포에서 염주괴불주머니 추출물의 MAPK 경로를 통한 MMP-2, MMP-9 발현 억제 효과)

  • Yu, Ga Hyun;Karadeniz, Fatih;Oh, Jung Hwan;Kong, Chang-Suk
    • Journal of Life Science
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    • v.32 no.1
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    • pp.51-55
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    • 2022
  • Matrix metalloproteinase (MMP) enzymes are responsible for the degradation and formation of the extracellular matrix (ECM), and overproduction of MMPs is observed in several diseases, such as cancer and asthma, that progress with metastatic characteristics. Natural products, especially phytochemicals, have been an important source of MMP inhibitors with reduced side effects. Although the majority of phytochemicals inhibit the enzymatic activity of MMPs, some suppress MMP production. In this context, the current study evaluated the potential of Corydalis heterocarpa, a halophyte with reported bioactivities, to inhibit MMP expression in PMA-stimulated HT-1080 cells. A crude C. heterocarpa extract was shown to decrease the mRNA and protein expression of MMP-2 and MMP-9 while increasing the endogenous MMP inhibitors TIMP-1 and TIMP-2 which regulate MMP expression in healthy tissues. In addition, our results show that the inhibitory effects of C. heterocarpa might occur through suppression of the phosphorylation of MAPK signaling, the upstream activator of MMP overexpression. In conclusion, C. heterocarpa is a potential source of antimetastatic compounds that might serve as lead molecules to develop novel MMP inhibitors.

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.

Inhibitory Effects of (-)Epigallocatechin Gallate and Quercetin on Phorbol 12-Myristate 13-Acetate-Induced Secretion of Metalloproteinase-2 and Metalloproteinase-9

  • Kang Sang-Wook;Choi Yean-Jung;Choi Jung-Suk;Kwon Hyang-Mi;Bae Ji-Young;Park Eun-Hee;Ji Geun-Eog;Kang Il-Jun;Kang Young-Hee
    • Nutritional Sciences
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    • v.9 no.3
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    • pp.145-151
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    • 2006
  • Matrix metalloproteinases (MMP) play an important role in the extracellular matrix (ECM) degradation undetphysiological and pathological conditions. The present study examined the influence of (-)epigallocatechin gallate and quercetin on phorbol-12-myristate 13-acetate (PMA)-induced secretion of MMP-2 and MMP-9, when human umbilical vein endothelial cells (HUVEC) were treated with (-)epigallocatechin gallate and quercetin at supraphysiological concentrations of $25{\mu}mol/L$. No cytotoxicity was observed by MIT assay in response to a treatment with PMA in the presence of (-)epigallocatechin gallate and quercetin. Western blot analysis and gelatin zymography revealed that exposure of HUVEC to PMA enhanced the levels and gelatinolytic activities of pro and active forms of MMP-2 and active form of MMP-9. (-)Epigallocatechin gallate attenuated PMA-stimulated secretion of active forms of MMP-2 and MMP-9 concomitantly with a loss of activities of these enzymes, which was related to the decreased mRNA levels of MMP. Quercetin was more potent than (-)epigallocatechin gallate in alleviating MMP-9 protein secretion and activity with a decrease in MMP-9 mRNA accumulation. Taken together, the results indicated that (-)epigallocatechin gallte and quercetin exhibited inhibitory effects on MMP activity and may qualify as chemopreventive and cardiovascular protective agents.