• Biomolecules & Therapeutics
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• 제20권1호
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• pp.57-61
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• 2012

The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [$H_2O_2$]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyfl avone) was investigated for its in vitro activity against $H_2O_2$-induced damage using a human skin keratinocyte model. Baicalein pretreatment signifi cantly inhibited $H_2O_2$-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6749-6751
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• 2015

Background: Laryngeal cancer is an important malignancy in head and neck area and squamous cell carcinoma (SCC) is the most common type accounting for 95% of cases. Increase in matrix metalloproteinases (MMPs) in different tumors and their correlation with tumor invasiveness has been documented. However, most studies have evaluated MMP-2 and MMP-9 expression and few have evaluated serum levels. The aim of current study was to evaluate serum levels in patients with laryngeal SCC compared to normal subjects and assess any relation with tumor clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included. Serum levels of MMP-2 and MMP-9 were compared between groups and correlations with findings including grade (T) and node involvement (N) were evaluated. Results: Patients with laryngeal SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p=0.03) compared to healthy subjects. Patients with higher T stage (T3,4) had significantly higher MMP-2 (p=0.04) and MMP-9 (p=0.01). There was significant positive correlation between serum levels of MMP-2 with T stage (r=0.45, p=0.04) and lymph node involvement (r=0.563, p=0.01) and between levels of MMP-9 with T stage (r=0.527, p=0.01). Conclusions: Our results showed that compared to healthy subjects, both MMP-2 and MMP-9 are significantly increased in serum of laryngeal SCC cases. MMP-2 was correlated with lymph node involvement while MMP-9 has stronger correlation with T stage compared to MMP-2.

• Nutritional Sciences
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• 제9권3호
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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.

• 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.

• Archives of Plastic Surgery
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• 제39권2호
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• pp.106-112
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• 2012

Background : Complicated diabetic patients show impaired, delayed wound healing caused by multiple factors. A study on wound healing showed that platelet-rich plasma (PRP) was effective in normal tissue regeneration. Nonetheless, there is no evidence that when platelet-rich plasma is applied to diabetic wounds, it normalizes the diabetic wound healing process. In this study, we have analyzed matrix metalloproteinase (MMP)-2, MMP-9 expression to investigate the effect of PRP on diabetic wounds. Methods : Twenty-four-week-old male Otsuka Long-Evans Tokushima Fatty rats were provided by the Tokushima Research Institute. At 50 weeks, wounds were arranged in two sites on the lateral paraspinal areas. Each wound was treated with PRP gel and physiologic saline gauze. To determine the expression of MMP-2, MMP-9, which was chosen as a marker of wound healing, reverse transcription polymerase chain reaction (RT-PCR) was performed and local distribution and expression of MMP-2, MMP-9 was also observed throughout the immunohistochemical staining. Results : RT-PCR and the immunohistochemical study showed that the levels of MMP-2, MMP-9 mRNA expression in PRP applied tissues were higher than MMP-2, MMP-9 mRNA expression in saline-applied tissues. MMP-9 mRNA expression in wounds of diabetic rats decreased after healing began to occur. But no statistical differences were detected on the basis of body weight or fasting blood glucose levels. Conclusions : This study could indicate the extracellular matrix-regulating effect observed with PRP. Our results of the acceleration of wound healing events by PRP under hyperglycemic conditions might be a useful clue for future clinical treatment for diabetic wounds.

• 한국산학기술학회논문지
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• 제14권11호
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• pp.5778-5784
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• 2013

본 연구는 항주름 소재를 개발하기 위해서 목단피로부터 gallic acid (GA)를 분리하여 항산화능을 측정하였고, HaCaT 세포에서 세포독성을 측정하였다. 또한 HaCaT 세포에서 tumor necrosis factor alpha (TNF-${\alpha}$)에 의해 유도되는 matrix metalloproteinase-1 (MMP-1) mRNA 발현, protein 발현, 분비에 대한 GA의 영향을 관찰하였다. 결과로써 GA는 30 ${\mu}g/mL$의 $IC_{50}$과 함께 항산화능을 나타내었고, 그것의 항산화능은 합성항산화제인 butylated hydroxyanisol (BHA)보다 높았다. GA는 HaCaT 세포에서 고농도인 200 ${\mu}g/mL$ 처리시 약한 세포독성을 나타내었다. 또한 HaCaT세포에서 TNF-${\alpha}$ (10 ng/mL)의 처리에 의해 증가된 MMP-1의 mRNA 발현, protein 발현, 분비는 GA의 처리에 의해 농도 의존적으로 유의적인 감소를 나타내었다(p<0.05). 그러므로 GA는 항산화 효과와 TNF-${\alpha}$로부터 유도되는 MMP-1의 발현을 저해함으로써 피부 주름을 개선할 수 있는 주름개선제로서의 활용가능성을 확인하였다.

• 대한화장품학회지
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• 제31권2호
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• pp.161-167
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• 2005

잎새버섯(Grifola frondosa HB0071)이 생산하는 세포외 다당체인 GF-glucan이 사람섬유아세포에서 자외선(UVA)조사 시 증가되는 MMP-1 발현에 미치는 영향을 조사하였다. 자외선으로부터 조사된 섬유아세포에 GF-glucan을 처리한 농도에 따라 MMP-1 발현이 억제되었으며, RT-PCR를 이용해 세포내 MMP-1 mRNA 발현 또한 감소하는 것으로 나타났다 즉, 최대 GF-glucan $0.5\%$를 처리했을 때 $54.4\%$의 MMP-1 발현을 억제하였다. 결과적으로, 잎새버섯 HB0071로부터 생산된 GF-glucan은 피부노화와 관련된 extracellular matrix (ECM) 조직에 손상을 주는 MMP-1의 활성을 억제하여 자외선으로부터 손상된 피부의 광노화로부터 보호해주는 것으로 밝혀졌다.

• 대한화장품학회지
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• 제40권4호
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• pp.365-371
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• 2014

새로운 주름개선제 성분을 찾기 위해서 본 연구에서는 사람 피부 섬유아세포의 세포독성, 콜라겐 생합성, matrix metalloproteinase-I (MMP-1) 및 elastase 저해활성에 대한 Lactobacillus plantarum으로 발효된 오미자 발효액의 주름개선 효과를 평가하였다. 먼저, 오미자 추출물은 L. rhamnosus으로 $37^{\circ}C$에서 1일 동안 발효하였다. 발효물의 세포독성은 cytopathic effect reduction 방법에 의해 평가하였다. 콜라겐 생합성에 대한 발효물의 영향은 procollagen type-IC peptide EIA kit에 의해 평가하였으며, matrix metalloproteinase-I(MMP-1)에 대한 발효물의 영향은 Matrix Metalloproteinase-1 Biotrack activity Assay Kit에 의해 평가하였다. Elastase inhibition assay는 기질로써 N-Suc-$(Ala)_3$-nitroanilide을 사용하여 기질 반응에 의해 평가하였다. 결과로써 오미자 발효물은 사람 피부 섬유아 세포에 대해 $100{\mu}g/mL$의 농도에서 세포독성을 나타내지 않았다. 또한 오미자 발효물은 콜라겐 생합성을 촉진시켰으며, MMP-1의 저해 효과를 나타내었다(p < 0.05). Elastase inhibition assay에서 오미자 발효물의 $IC_{50}$은 $36.4{\mu}g/mL$이었다. 그러므로 본 연구에서 오미자 발효물은 주름개선 효과를 보유하고 있으며, 이것은 피부의 주름개선을 위해 사용가능하리라 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제11권3호
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• pp.85-88
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• 2007

Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. $15{\sim}30min$ prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. $15{\sim}30min$ prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG ire mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.

• 생약학회지
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• 제33권2호통권129호
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• pp.137-143
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• 2002

The inhibitory effects of methanol extracts of 165 medicinal herbs on matrix metalloproteinase-2 (MMP-2) activity were investigated. Amongst the herbal extracts, Youngia denticulate, Platycarya strobilacea, Sedum kamtschaticum, Euscaphis japonica, and Comus controversa showed a significant inhibitory effect with above 80% at $1\;{\mu}g/ml$. Above mentioned five kind extracts, which exclude polyphenols and/or tannin by techniques for their removal, showed a mild inhibitory effect on MMP-2 activity except for Y. denticulate at the same concentration.