• Perinatology
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• 제29권4호
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• pp.170-174
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• 2018

Objective: Progesterone is used to prevent recurrent preterm delivery, however the molecular mechanisms of its effect are incompletely understood. The objective of this study was to determine the effect of progesterone on tumor necrosis factor $(TNF)-{\alpha}$-induced matrix metalloproteinase (MMP)-9 activity in human choriodecidual (CD) membranes. Methods: We collected CD membranes from women with uncomplicated term pregnancies who were scheduled for elective cesarean delivery (n=10). CD membranes ($1{\times}1cm$) were incubated in tissue culture media at $37^{\circ}C$. We pre-treated the CD membranes with progesterone (P4), $17{\alpha}$-hydroxyprogesterone caproate (17P), promegestone (R5020), or vehicle (ethanol) for 24 hours. The CD membranes were subsequently treated with $TNF-{\alpha}$ (with continued progesterone treatment) for 48 hours, then media was harvested for measuring MMP-9 activity by zymography and total protein was isolated from CD membrane tissues for MMP-9 expression by western blot analysis. Results: P4, 17P, and R5020 significantly reduced $TNF-{\alpha}$-induced MMP-9 activity in fetal membrane tissue samples (P=0.0078, P=0.0156, and P=0.0391, respectively) by zymography. Western blot analysis also showed decreased expression of MMP-9 in progesterone pretreated groups (P=0.0313). Conclusion: Progesterone reduces $TNF-{\alpha}$-induced MMP-9 activity in human CD membranes. These findings may provide further support for the role of progesterone in preventing preterm birth.

• 한국균학회지
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• 제45권3호
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• pp.175-187
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• 2017

Laetiporus sulphrueus var. miniatus is widely distributed worldwide, and has commonly been used as a medicinal mushroom. In the present study, we investigated the effects of water extract and solvent fractions from the Laetiporus miniatus as possible antioxidant, anti-thrombin and anti-invasive agents against phorbol 12-myristate 13-acetate (PMA)- or thrombin-induced matrix metalloproteinase-2 (MMP-2) and MMP-9 activities. Samples were fractionated into n-hexane, $CHCl_3$, ethyl acetate, n-butanol, and water fractions, and individually analysed. The water fraction had the highest extraction yield at 34.90% (w/w), while the n-butanol fraction demonstrated the highest anti-oxidative activity at 81.44%. In the thrombin inhibitory activity test, the water fraction exhibited the highest activity at 94.64%. Even at the concentration of $40{\mu}g/mL$, evaluation of anti-proliferating activity in YD-10B cells did not reveal any cytotoxic effects. Although MMP-9 expression in YD-10B cells increased after the addition of PMA and thrombin, MMP-2 did not. Additionally, MMP-2/-9 levels in PMA-treated YD-10B cells (i.e., both mRNA expression and protein activation) were highly inhibited in the hexane and chloroform fractions. Compared with MMP-2 levels, MMP-9 mRNA expression and proteolytic activity were inhibited to a greater extent by the hexane and chloroform fractions in thrombin-treated YD-10B cells. Taken together, these results support that thrombin induces tumor invasion through MMP-2/9 and suggest that the L. miniatus may act as an effective functional food, conferring anti-oxidative, anti-thrombotic and anti-cancer activities.

• 동의생리병리학회지
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• 제22권6호
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• pp.1470-1474
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• 2008

This study was performed to examine the anti-metastatic effect of ethanol extract of Samguikoeui-Tang (SGKE), a formula consisting of four oriental herbs, in highly-metastatic HT1080 human fibrosarcoma cells. SGKE significantly inhibited the adhesion of HT1080 cells to matrigel at nontoxic concentrations in a dose-dependent manner, while it did not exert cytotoxicity against HT1080 cells up to the concentration of 100 ${\mu}g$/ml. Also, SGKE depressed the activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by gelatin zymography. However, SGKE did not affect the mRNA expression of MMP-2 and TIMP-2, an inhibitor of MMP-2, by RT-PCR analysis. In addition, the effect of SGKE on HT1080 cell invasion was determined using Boyden chamber assay. SGKE suppressed the invasion of HT1080 cells in a dose-dependent manner. Taken together, these results suggest that SGKE has an anti-metastatic effect via inhibition of MMP-2 and -9 activities.

• BMB Reports
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• 제50권12호
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• pp.628-633
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• 2017

Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase-2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation.

• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.82-89
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• 2006

최근 여러 종양에서 단백분해효소의 분비와 암의 악성도에 대한 연구가 이루어져 왔으며, 이를 신세포암종 환자의 예후 측정인자로 사용하려는 시도가 진행되고 있다. 이에 저자들은 제 4형 collagenase 중 대표적인 MMP-9의 발현정도를 정상 신조직과 신세포암종 조직에서 비교하였고, 또 암의 침윤 및 전이정도와의 관계와 다른 임상적 인자들과의 상관성을 분석하여 암의 단계적 진행과정에서의 MMP-9의 발현변화에 대하여 조사하였다. 그 결과 정상 신 조직에 비해 신세포암종 조직에서 MMP-9의 발현이 증가되며 암의 크기가 크고 혈관침범이 있으며 병기가 높을수록 MMP-9의 발현이 증가됨을 관찰할 수 있었다. 이는 MMP-9 발현의 증가가 신세포암종의 발생과정 및 암의 후기 진행에 관여함을 시사하므로 향후 신세포암종의 예후척도로 사용되어 치료방침을 결정하는데 도움을 줄 수 있을 것으로 생각한다.

• Journal of Nutrition and Health
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• 제36권3호
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• pp.280-286
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• 2003

Conjugated linoleic acid (CLA) consists of several geometric isomers of linoleic acid. CLA is found in foods derived from ruminants and exhibits strong anticarcinogenic effects in a variety of animal models. Matrix metalloproteinases (MMPs) play a key role in cancer progression. Specifically, MMP-2 and -9, which hydrolyze the basal membrane type IV collagen, are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. However, the effects of CLA on cancer cell motility and MMP expression and activity are not currently well known. Therefore, the present study examined whether CLA reduces the activity of MMP and cell motility in SW480 and SW620 cells, the human colon cancer cell lines. Gelatin zymography and Western blot analysis revealed that phorbol 12-myristate 13-acetate (PMA) induced the activity and protein expression of Mr 92,000 MMP-9 in both cell lines. To examine whether CLA inhibits the MMP activity, cells were incubated with 100 ngfmL PMA in the presence of various concentrations of CLA. PMA-induced MMP-9 activity was decreased by 20 $\mu$ M CLA in SW480 cells, and by 10 $\mu$ M and 20 $\mu$ M CLA in SW620 cells. Results from the Hoyden chamber assay showed that cell motility was increased by PMA and that PMA-induced cell motility was significantly decreased by 20 $\mu$ M CLA in SW480 cells. These results indicate that CLA may reduce the motility and MMP activity in human colon cancer cells.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.510-518
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• 2010

목 적: 가와사끼병은 급성 전신성 미세혈관염으로서, 소아의 후천성 심질환의 가장 흔한 원인이다. 가와사끼병의 관상동맥병변에 대한 조직병리학적 소견은 미만성 혈관염에 의한 관상동맥벽의 파괴를 시사하는데, matrix metalloproteinase (MMP)와 그 내인성 억제인자인 tissue inhibitor of metalloproteinases (TIMP)가 이러한 과정에 주요한 역할을 할 것으로 생각되고 있으며, 그 중에도 MMP-9이 최근 가장 주목을 받고 있다. 따라서 본 연구에서는, 한국의 가와사끼병 환아들에서 MMP-9과 그 억제인자들인 TIMP-1, TIMP-2가 갖는 임상적 중요성을 평가하고자 하였다. 방 법: 가와사끼병 환아 47명을 연구대상으로 하였고, 급성열성 세균감염 환아 14명을 대조군으로 하였다. 혈중 MMP-9, TIMP-1, TIMP-2의 농도를 kit를 통한 효소 면역법을 이용하여 측정하였고, 각 임상 단계 및 관상동맥병변의 유무에 따라 비교분석하였다. 결 과: 급성기에 MMP-9과 TIMP-1은 가와사끼군에서 대조군에 비해 유의하게 높았고, TIMP-2는 오히려 낮았다($P$<0.05). 급성기에 증가한 MMP-9은 아급성기와 회복기에 유의하게 감소하였다($P$<0.05). 관상동맥 확장군과 비확장군의 비교에서는, 확장군에서 급성기 MMP-9과 TIMP-1, MMP-9/TIMP-2가 낮았으며, 아급성기로 가면서 통계적으로 유의하게 증가하였다가 다시 회복기로 가면서 감소하는 양상을 보였다($P$<0.05). MMP-9은 급성기와 아급성기에 TIMP-1과 통계적으로 유의한 양의 상관관계를 보였고, TIMP-2와는 아급성기와 회복기에 음의 상관관계를 보였다($P$<0.05). 결 론: 이러한 결과들은 MMP-9과 TIMP-1의 증가, 그리고 MMP-9과 TIMP-2의 불균형이 가와사끼병, 특히 그 관상동맥병변의 병태생리에 핵심적인 역할을 한다는 사실을 시사한다 하겠다. 더 종합적이고 심도 깊은 연구를 위해서 좀 더 많은 대상자를 포함하는 큰 규모의 연구들이 향후 이루어져야 할 것이다.

• 생명과학회지
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• 제24권6호
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• pp.700-706
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• 2014

본 연구에서는 anthracycline 계열 항암항생제인 doxorubicin의 암세포 전이 억제 여부를 LNCap 전립선 암세포를 이용하여 이동성 및 침윤성 억제 효능 측면에서 조사하였다. 본 연구의 결과에 의하면 doxorubicin은 LNCap 세포의 이동성과 침윤성을 현저하게 억제시켰으며, matrix metalloproteinase (MMP)-2 및 -9의 발현과 활성을 저해함과 동시에 tissue inhibitor of metalloproteinase (TIMP)-1 및 -2의 발현은 증가시켰다. Doxorubicin은 또한 tight junctions (TJs)의 전기적 저항성을 증대시켰으며, 이는 TJs의 주요 구성인자인 claudin family 인자들의 발현 억제와 연관성이 있었다. 따라서 LNCap 세포에서 doxorubicin에 의한 전이의 억제에는 최소한 TJ의 견고성 증대와 MMPs의 활성 억제가 관여할 것으로 추정된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.1049-1052
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• 2012

The purpose of this study was to evaluate expression and prognostic value of matrix metalloproteinase-7 (MMP-7) in colorectal cancer (CRC) patients. CRC tissues and corresponding distal normal mucosa tissues of 118 CRC patients were assessed by immunohistochemistry. Correlations between MMP-7 expression, patients' clinic pathological features, and overall survival rate were analyzed. We found that positive expression of MMP-7 in CRC tissues was significantly higher than that in distal normal mucosa (61.0% vs. 39.8%, p =0.001). Poor histological differentiation, advanced clinical stage and lymph node metastasis were significantly correlated with MMP-7 expression in CRC. The overall survival rate was significantly higher in the MMP-7 negative group than the positive group (Log-rank test= 9.957, p= 0.002). MMP-7 appeared as a significant independent prognostic factor through multivariate survival analysis. Collectively, we found MMP-7 expression to be correlated with progression and metastasis of CRC and thus could be used as a predictive marker of prognosis in CRC patients.

• 생명과학회지
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• 제23권3호
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• pp.355-360
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• 2013

Withaferin A는 Withania somnifera라는 식물에서 추출한 스테로이드 락톤으로 항염증, 항암, 그리고 면역중재 작용과 같은 다양한 역할을 한다. 그러나, withaferin A에 의한 MMP-9의 발현 및 활성화 조절에 대한 연구는 수행되지 않았다. 본 연구에서 우리는 withaferin A가 인간 자궁경부암세포인 Caski세포에서 PMA 매개의 MMP-9의 발현과 활성화를 조절 할 수 있는지 확인하였다. Withaferin A는 농도의존적으로 PMA유도 MMP-9의 활성을 억제하였고, MMP-9의 promoter assay를 통하여 전사단계에서 조절됨을 확인하였다. 또한, Withaferin A 의한 PMA 유도 MMP-9의 mRNA와 단백질 발현이 억제됨을 확인하였다. 이러한, withaferin A에 의한 MMP-9 발현 조절 전사인자로는 NF-${\kappa}B$가 관여함을 확인하였다. Withaferin A는 PMA에 의한 세포이동을 억제하였는데, 이러한 현상은 MMP-9의 발현 및 활성을 조절함으로써 일어날 수 있음을 확인하였다.