• 대한의생명과학회지
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• 제10권2호
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• pp.143-151
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• 2004

Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, a process that is necessary for angiogenesis, tumor invasion and metastasis. Platelet-activating factor (PAP) increases angiogenesis, tumor growth and metastasis through nuclear factor (NF)-$\kappa$B activation. Based on these facts, the involvement of MMPs in PAF-induced pulmonary metastasis was investigated in murine sarcoma cells, MMSV-BALB/3T3. Messenger RNA expression and enzymatic activity of MMP-9 were assessed by RT-PCR and zymography, and cell migration and metastasis were done for the detection of MMP-9 functional activity. PAP induced mRNA expression and enzymatic activity of MMP-9, and its effects were either inhibited by the PAP antagonist, WEB 2170 or by the NF-$\kappa$B inhibitor, parthenolide, or p65 antisense oligonucleotide in a dose-dependent manner. In addition, PAF induced promoter activity of MMP-9, which was inhibited by WEB 2170, phenanthroline, NAC, PDTC. These results indicate that PAF induces mRNA expression and enzymatic activity of MMP-9 in NF-$\kappa$B dependent manner. Cell migration assay showed that PAF induced MMSV-BALB/3T3 migration, and its effect was significantly inhibited by treatment with phenanthroline. PAF enhanced pulmonary metastasis of murine sarcoma cells, MMSV-BALB/3T3 was also reduced by phenanthroline. These results suggest that PAF-enhanced cell migration and pulmonary metastasis is mediated through the expression of MMP. In conclusion, It is suggested that PAF enhances pulmonary metastasis by inducing MMP-9 expression via the activation of NF-$\kappa$B.

• 대한화장품학회지
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• 제30권2호
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• pp.247-251
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• 2004

자외선은 피부에 염증반응이나 광노화와 같은 다양한 반응을 야기시킨다고 알려져 있다. 특히 자외선에 의해 손상을 받은 피부는 콜라겐의 양이 감소되어 있는데, 이는 자외선에 의해 피부 내에서 콜라겐을 분해하는 효소(MMP, matrix metalloproteinases)의 양이 증가하기 때문이라고 알려져 왔다. 또한 자외선에 의해 피부에서 염증반응이 유발되는데, 이러한 반응은 프로스타글란딘이라는 물질에 의해 매개되며, 이 프로스타글란딘에 의해서도 MMP가 증가한다고 알려져 왔다. 본 연구에서는 6개월의 임상실험을 통해 광노화된 피부에서 주름형성억제효능이 뛰어난 FDP(fructose 1.6-diphosphate)의 작용기전을 인체각질형성 세포를 이용하여 연구하였다. 인체각질형성세포에 자외선을 조사할 경우 프로스타글란딘, COX-2(cyclooxygenase-2), MMPs의 활성이 증가하는 것을 확인하였며, 이는 FDP의 처리에 의해 감소되었다. 이러한 효과는 자외선에 의해 인체각질형성세포에서 발생하는 신호전달과정을 억제함으로써 일어나는 효과임이 증명되었다. 따라서, FDP는 자외선에 의해 일어나는 세포 내 신호전달과정을 억제하며, 이로 인해 야기되는 프로스타글란딘, COX-2, MMPs의 증가를 억제함으로써 피부의 광노화를 억제할 수 있는 원료로 여겨진다.

• Animal Bioscience
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• 제36권8호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1263-1267
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• 2014

Background: Matrix metalloproteinases (MMPs) play important roles in pathogenesis and development of cancer. Recently, many studies have show associations between polymorphisms in the promoter regions of MMPs and risk of gastric cancer. The present meta-analysis was conducted in order to investigate the potential association between four polymorphisms in the MMP gene and gastric cancer risk. Methods: A computerized literature search was conducted in databases of Med-line, Embase, Science Citation Index and PubMed till June 2013 for any MMP genetic association study of gastric cancer. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated for each gene under dominant and recessive models, and heterogeneity between studies was assessed using the Q test and $I^2$ value. Overall and subgroup analyses according to ethnicity were carried out with Stata 12.0. Results: 14 reports covering 8,146 patients (2,980 in the case group and 5,166 in the control group) were included in the present meta-analysis. We found that the MMP-7 (-181A>G) polymorphism increased the gastric cancer risk in therecessive model (GG vs. AA/AG, OR=1.768, 95% CI =1.153-2.712). For MMP2 -1306 C>T, MMP1-1607 1G/2G, and MMP9-1 562 C>T, there were no associations between these polymorphisms and the risk of gastric cancer under dominant or recessive models. Conclusion: This meta-analysis suggested that the MMP7-181 A>G polymorphism may contribute to gastric cancer susceptibility. More studies are needed, especially in Europeans, in the future.

• BMB Reports
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• 제45권11호
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• pp.623-628
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• 2012

Tissue inhibitor of metalloproteinases (TIMPs; TIMP-1, -2, -3 and -4) are endogenous inhibitor for matrix metalloproteinases (MMPs) that are responsible for remodeling the extracellular matrix (ECM) and involved in migration, invasion and metastasis of tumor cells. Unlike under normal conditions, the imbalance between MMPs and TIMPs is associated with various diseased states. Among TIMPs, TIMP-1, a 184-residue protein, is the only N-linked glycoprotein with glycosylation sites at N30 and N78. The structural analysis of the catalytic domain of human stromelysin-1 (MMP-3) and human TIMP-1 suggests new possibilities of the role of TIMP-1 glycan moieties as a tuner for the proteolytic activities by MMPs. Because the TIMP-1 glycosylation participate in the interaction, aberrant glycosylation of TIMP-1 presumably affects the interaction, thereby leading to pathogenic dysfunction in cancer cells. TIMP-1 has not only the cell proliferation activities but also anti-oncogenic properties. Cancer cells appear to utilize these bilateral aspects of TIMP-1 for cancer progression; an elevated TIMP-1 level exerts to cancer development via MMP-independent pathway during the early phase of tumor formation, whereas it is the aberrant glycosylation of TIMP-1 that overcome the high anti-proteolytic burden. The aberrant glycosylation of TIMP-1 can thus be used as staging and/or prognostic biomarker in colon cancer.

• Clinical and Experimental Reproductive Medicine
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• 제25권2호
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• pp.161-170
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• 1998

Protein expression patterns of matrix metalloproteinases (MMPs) were examined in mouse reproductive organs during estrous cycle. Estrous cycle was classified into diestrus, proestrus, estrus or metestus and MMP expression was analyzed by zymography using gelatin as a substrate. Uterine fluid (UF) obtained both at diestrus and proestrus exhibited 4 major MMPs including 106kDa, 64kDa, 62kDa and 59kDa gelatinases. However, in UF at estrus, the gelatinolytic activity of 64kDa MMP disappeared and that of 106kDa and 62kDa MMPs dramatically decreased. At metestrus, 64kDa MMP activity reappeared and 106kDa and 62kDa MMP exhibited increased activities such that the band intensity of 106kDa was comparable to that in UF at diestrus. Gelatinolytic activity of 59kDa MMP was not changed throughout the cycle. Both ovarian and oviductal tissue homogenate revealed 4 MMPs which corresponded to the 4 MMPs of UF. However, unlike UF MMPs, gelatinolytic activity of these MMPs did not show distinct changes throughout the cycle. Either an inhibitor of MMP, 1,10-phenanthroline, or a metal chelator, EDTA, abolished the appearance of the above MMP activities in gelatinated gel whereas a serine proteinase inhibitor, phcnylmethylsulfonyl fluoride, failed to inhibit the appearance of MMP activities, proving that gelatinolytic activity of the above reproductive tissues were due to the enzymatic activity of MMP. When gclatinolytic activity of mouse serum was examined, it revealed 5 MMPs (131kDa, 106kDa, 89kDa, 64kDa and 62kDa bands) and one gelatinase (84kDa) band. From these results, it is concluded that the protein expression of MMPs of mouse reproductive organs, particularly uterus, is temporally regulated during estrous cycle and uterine 106kDa, 64kDa and 62kDa MMPs are suggested to play an important role in cyclic tissue remodeling of mouse uterus.

• 생명과학회지
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• 제22권7호
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• pp.964-969
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• 2012

Genistein은 대두 및 그들의 부산물에 풍부하게 존재하는 isoflavone의 일종으로 정상세포에서는 독성을 나타내지 않는 범위에서 다양한 in vitro 및 in vivo 모델에서 암세포의 증식을 효과적으로 억제할 수 있는 천연물로 알려져 있다. 본 연구에서는 MCF-7 및MDA-MB-231 유방암세포에서 matrix metalloproteinases (MMPs)의 활성 및 발현과 침윤성에 미치는 genistein의 영향을 조사하였다. 본 연구의 결과에 의하면 genistein은 12-O-tetradecanoyl phorbol-13-acetate (TPA) 처리에 의하여 활성화된 MMP-2 및 -9의 활성을 유의적으로 차단하였으며, 이는 전사 및 번역 수준에서 MMP-2 및 -9의 발현 억제와 연관성이 있었다. 또한 matrigel invasion assay를 통하여 genistein은 두 유방암세포의 침윤성을 완벽하게 차단하였음을 관찰하였으며, 이러한 효과는 genistein의 세포독성 효과에 의한 것이 아니었음을 알 수 있었다. 비록 in vivo 동물 실험을 통한 부가적인 연구의 필요성이 있으나, 본 연구의 결과는 genistein이 암의 전이를 억제할 수 있는 효과적인 식이 소재임을 보여주는 것이다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.68.3-69
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• 2003

Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis by extracellular matrix degradation. To analyze the effect of DA-125, a anthracyclin derivative, on the invasion or metastasis of cancer cells the expression of matrix metalloproteases (MMPs) was investigated in human fibrosarcoma HTl080 cells by RT-PCR or gelatin zymographic methods. As result, DA-125 suppressed the expression of MMP-2 and 9 as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) TIMP-2 and MT1-MMP with a time- and dose-dependent manner. Inaddition, DA-125 inhibited cancer cell migration and colony formation, and also exhibited the inhibitory activities of invasion and motility with a matrigel and type I collagen assay. (omitted)

• Journal of Plant Biotechnology
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• 제31권4호
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• pp.313-317
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• 2004

MMPs는 $Zn^{2+}$-의존성 endopeptidase로서 세포외 기질을 분해하는 능력을 갖고 있다. 본 연구에서는 담배식물체에서 잎의 발생단계별로 분비되는 MMPs의 활성과 환경 스트레스에 의한 MMPs의 활성을 조사하였다. 그 결과 MMPs의 활성은 기부 부위의 완전히 성숙한 잎보다 엽신의 확장이 일어나고 있는 어린잎에서 높았다. 이는 식물체에서 잎 신장을 위한 세포내 공간 형성 및 조직재구성에 MMPs가 중요한 단백질분해효소로 작용함을 시사하였다. 또한 환경 스트레스에 대한 반응으로서 MMPs의 활성을 조사한 결과 염처리와 병원균 감염에 의해 각각 1.2배와 1.5배의 증가를 보였다. 이러한 결과는 식물체가 발생단계 외에도 불리한 환경에 대한 방어 수단으로 MMPs가 생성 분비함을 알 수 있었다.

• 통합자연과학논문집
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• 제4권4호
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• pp.255-265
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• 2011

Marine ecosystems are often characterized by a high biological diversity, and it corresponds to a high chemical diversity. Up to present, more than 20,000 new bioactive substances have been isolated from marine organisms, where considerable numbers of these naturally occurring derivatives are developed as potential candidates for pharmaceutical application. In this process, screening of natural products from marine organisms that could potentially inhibit the expression of metalloproteinases has gained a huge popularity. Cancer is considered as one of the deadliest diseases in the medical field. Matrix metalloproteinase (MMPs) can degrade extracellular matrix (ECM) components and play important roles in a variety of biological and pathological processes. Matrix metalloproteinase inhibitors (MMPIs) have been identified as potential therapeutic candidates for metastasis, arthritis, chronic inflammation and wrinkle formation.