• Title/Summary/Keyword: matrix metalloproteinase (MMP)

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Clinical Implication of Aortic Wall Biopsy in Aortic Valve Disease with Bicuspid Valve Pathology

  • Kim, Yong Han;Kim, Ji Seong;Choi, Jae-Woong;Chang, Hyoung Woo;Na, Kwon Joong;Kim, Jun Sung;Kim, Kyung-Hwan
    • Journal of Chest Surgery
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    • v.49 no.6
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    • pp.443-450
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    • 2016
  • Background: Although unique aortic pathology related to bicuspid aortic valve (BAV) has been previously reported, clinical implications of BAV to aortopathy risk have yet to be investigated. We looked for potential differences in matrix protein expressions in the aortic wall in BAV patients. Methods: Aorta specimens were obtained from 31 patients: BAV group (n=27), tricuspid aortic valve (TAV) group (n=4). The BAV group was categorized into three subgroups: left coronary sinus-right coronary sinus (R+L group; n=13, 42%), right coronary sinus-non-coronary sinus (R+N group; n=8, 26%), and anteroposterior (AP group; n=6, 19%). We analyzed the expression of endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2. Results: Based on the mean value of the control group, BAV group showed decreased expression of eNOS in 72.7% of patients, increased MMP-9 in 82.3%, and decreased TIMP in 79.2%. There was a higher tendency for aortopathy in the BAV group: eNOS $(BAV:TAV)=53%{\pm}7%:57%{\pm}11%$, MMP-9 $(BAV:TAV)=48%{\pm}10%:38%{\pm}1%$. The AP group showed lower expression of eNOS than the fusion (R+L, R+N) group did; $48%{\pm}5%$ vs. $55%{\pm}7%$ (p=0.081). Conclusion: Not all patients with BAV had expression of aortopathy; however, for patients who had a suspicious form of bicuspid valve, aortic wall biopsy could be valuable to signify the presence of aortopathy.

Assessment of MMP-1, MMP-8 and TIMP-2 in experimental periodontitis treated with kaempferol

  • Balli, Umut;Cetinkaya, Burcu Ozkan;Keles, Gonca Cayir;Keles, Zeynep Pinar;Guler, Sevki;Sogut, Mehtap Unlu;Erisgin, Zuleyha
    • Journal of Periodontal and Implant Science
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    • v.46 no.2
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    • pp.84-95
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    • 2016
  • Purpose: The objective of this study was to investigate the effect of a dietary flavonoid, kaempferol, which has been shown to possess antiallergic, anti-inflammatory, anticarcinogenic, and antioxidant activities on the periodontium by histomorphometric analysis and on gingival tissue matrix metalloproteinase-1 (MMP-1), MMP-8, and tissue inhibitor of metalloproteinase-2 (TIMP-2) by biochemical analysis of rats after experimental periodontitis induction. Methods: Sixty Wistar rats were randomly divided into six groups of ten rats each, and silk ligatures were placed around the cervical area of the mandibular first molars for 15 days, except in the healthy control rats. In the experimental periodontitis groups, systemic kaempferol (10 mg/kg/2d) and saline were administered by oral gavage at two different periods (with and without the presence of dental biofilm) to all rats except for the ten non-medicated rats. Alveolar bone area, alveolar bone level, and attachment level were determined by histomorphometric analysis, and gingival tissue levels of MMP-1, MMP-8, and TIMP-2 were detected by biochemical analysis. Results: Significantly greater bone area and significantly less alveolar bone and attachment loss were observed in the kaempferol application groups compared to the control groups (P<0.05). In addition, gingival tissue MMP-1 and -8 levels were significantly lower in the kaempferol application groups compared to the control groups and the periodontitis group (P<0.001). There were no statistically significant differences in TIMP-2 levels between the kaempferol and saline application groups (P>0.05). Conclusions: Kaempferol application may be useful in decreasing alveolar bone resorption, attachment loss, and MMP-1 and -8 production in experimental periodontitis.

The cancer/testis antigen CAGE induces MMP-2 through the activation of NF-κB and AP-1

  • Kim, Young-Mi;Jeoung, Doo-Il
    • BMB Reports
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    • v.42 no.11
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    • pp.758-763
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    • 2009
  • Cancer-associated antigen (CAGE) induces the expression of matrix metalloproteinase-2 (MMP-2) by activating Akt, which in turn interacts with inhibitory kappa kinase $\beta$ ($I{\kappa}K{\beta}$) to activate nuclear factor ${\kappa}B$ (NF-${\kappa}B$). Akt and p38 mitogen activated protein kinase (p38 MAPK) are necessary for CAGE-mediated induction of the AP-1 subunit JunB, whereas extracellular regulated kinase (ERK) is necessary for the induction of fos-related antigen-1 (Fra-1). Induction of MMP-2 by CAGE requires activator of protein-1 (AP-1) to be bound. Specific binding of JunB to MMP-2 promoter sequences was shown by chromatin immunoprecipitation (ChIP) analysis.

Lonicerae Flos Inhibited COX-2 and MMP-9 in LPS Induced Arthritis of Mouse through Regulation of MIF (LPS 유도 생쥐 관절염에서 금은화의 MIF 활성 조절이 COX-2와 MMP-9 생성 억제에 미치는 영향)

  • Ahn, Sang-Hyun;Kim, Ho-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.2
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    • pp.242-248
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    • 2010
  • The present study was designed in order to determine whether Lonicerae flos (LF) could mitigate rheumatoid arthritis through inhibition of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 by regulation of macrophage migration inhibitory factor (MIF). We found that MIF mRNA expression in synoviocytes stimulated with phorbol-12-myristate-13-acetate dose-dependantly decreased by LF extract treatment (0.4 - 1.0 mg/$m{\ell}$). The distribution of MIF, COX-2 and MMP-9 positive reacted cells in LPS induced arthritis of mice were decreased by LF (45 mg/kg/day) treatment for 28 days. These data likely indicate that LF may act as MIF inhibitor and may be possible to develop useful agent for rheumatoid arthritis.

Matrix metalloproteinase-8 and substance P levels in root canal exudates of nonvital teeth (근관 삼출액에서의 기질금속단백분해효소-8과 substance P의 수준에 관한 연구)

  • Shin, Su-Jung;Lee, Woo-Cheol;Lee, Jae-Il;Baek, Seung-Ho;Kum, Kee-Yeon;Shon, Won-Jun;Bae, Kwang-Shik
    • Restorative Dentistry and Endodontics
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    • v.36 no.3
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    • pp.196-202
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    • 2011
  • Objectives: The aim of this study was to investigate levels of matrix metalloproteinase-8 (MMP-8) and substance P (SP) in root canal exudates during root canal treatment (RCT) of nonvital, painful teeth. Materials and Methods: Patients scheduled for nonsurgical RCT were prospectively selected; the study was performed after obtaining informed consent from the patients and was approved by the Institutional Review Board for Clinical Research of Gangnam Severance Hospital, Yonsei University (3-2008-0118). Canal exudates samples were collected using sterilized paper points from teeth scheduled for RCT across three different time periods. MMP-8 and SP levels were measured using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using a mixed model analysis and the Pearson correlation analysis (p < 0.05). Results: MMP-8 and SP levels in GCF were decreased during RCT (p < 0.0001), and they showed a weak positive correlation to each other (p < 0.05). Patients' subjective pain levels and the response from percussion test were significantly related to SP level. Conclusions: This study demonstrated that periradicular inflammation endodontic origin can elevate SP and MMP-8 levels in root canal exudates. Interestingly, SP level of canal exudates showed a possibility of being used as an indicator of pain due to periapical pathosis.

Effect of Asterina pectinifera on Activities of Breast Cancer Chemopreventive and Metastatic Enzymes (별불가사리 단백추출물이 유방암예방 및 전이억제 효소계에 미치는 영향)

  • Nam, Kyung-Soo;Kim, Mee-Kyung;Cho, Hyun-Jung;Shon, Yun-Hee
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.3
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    • pp.193-197
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    • 2006
  • The effect of protein extract from Asterina pectinifera on breast cancer chemopreventive (aromatase and cyclooxygenase-2) and metastatic (matrix metalloproteinase) enzymes was tested. Protein extract from A. pectinifera was capable of suppressing aromatase in a human placenta microsomal assay. Cyclooxygenase-2 (COX-2) activity was significantly inhibited by the protein extract from A. pectinifera at concentrations of 10, 20 and $40{\mu}g/m{\ell}$. The extract markedly reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated matrix metalloproteinase (MMP)-9 activity. These results suggest that A. pectinifera could be of therapeutic value in preventing human breast cancer.

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Expression Profiles of Secretory Leucocyte Protease Inhibitor, MMP9, and Neutrophil Elastase in the Mouse Uterus

  • Cheon, Yong-Pil
    • Development and Reproduction
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    • v.14 no.3
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    • pp.207-214
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    • 2010
  • The tremendous changes of uterine endometrium are observed during early pregnancy and protease and their inhibitors are involved in regulation of cell proliferation and remodeling of the tissues through remodeling the extracellular matrix (ECM). Some of the proteases and protease inhibitors have been suspected to a factor in endometrial changes but many parts of their expression profiles and the physiological roles are not uncovered. To evaluate the functional roles of them, in this study the expression profiles of proteases and protease inhibitors were analyzed using real-time quantitative PCR analysis. Mmp9 (matrix metalloproteinase 9) mRNA levels peaked on day 4 at the time of implantation. On the other hand, Ela2 (neutrophil elastase, NE) mRNA levels were peaked on day 2 of pregnancy. Its expression were decreased until day 4 of pregnancy but increased rapidly until day 7 of pregnancy and decreased again. NE inhibitor Slpi (secretory leukocyte protease inhibitor, SLPI) mRNA levels were related with the implantation stage and with the levels of Ela2. At the time of implantation the expression levels of Slpi mRNA were about 5 times higher than the Ela2 mRNA in the uterus. In the implantation stage embryos, Mmp9 specific mRNA was only detected at the blastocyst. On the other hand, the expression level of SLPI was higher than that of the Ela2 mRNA at blastocyst and 4.5 day p.c. embryos. Based on these results it is suggested that MMP9, SLPI, and NE have important physiological role in embryo implantation both in uterus and embryos.

Indole-6-carboxaldehyde isolated from Sargassum thunbergii inhibits the expression and secretion of matrix metalloproteinase-9

  • Tae‑Hee Kim;Soo-Jin Heo;Seok-Chun Ko;Won Sun Park;Il-Whan Choi;Myunggi Yi;Won-Kyo Jung
    • International Journal of Molecular Medicine
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    • v.44 no.5
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    • pp.1979-1987
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    • 2019
  • Sargassum thunbergii is a brown alga from which various bioactive compounds can be extracted. Among these, the activities of indole derivatives, particularly as potential inhibitors of matrix metalloproteinases (MMPs), and their underlying mechanisms have been rarely investigated. Therefore, we evaluated the inhibitory effects of indole-6-carboxaldehyde (I6CA) on MMP-9 by gelatin zymography and western blot anlaysis. We used phorbol 12-myristate 13-acetate (PMA), which is known to induce MMP-9 expression and secretion, to stimulate HT1080 cells. Our results revealed that I6CA significantly inhibited MMP-9 expression and secretion, without significantly affecting the viability of PMA-stimulated HT1080 cells. Our mechanistic studies indicated that I6CA suppressed the phosphorylation and activation of two mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK). Furthermore, I6CA inhibited the phosphorylation of inhibitor of κBα (IκBα) in response to PMA stimulation, which suppressed nuclear factor-κB (NF-κB) p65 subunit nuclear translocation. Collectively, I6CA was determined to suppress MMP-9 expression and secretion, and effects were proposed to be mediated via the inhibition of the MAPK and NF-κB p65 pathways. Therefore, we suggested I6CA to be a potential therapeutic agent for MMP-9-related processes, including tumor invasion and metastasis; however, further investigation is required.