• 약학회지
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• 제50권4호
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• pp.228-233
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• 2006

Matrix metalloproteinase-2 is known to be involved in pathological processes such as tumor invasion or rheumatoid arthritis. A soil microorganism producing siderophore under low iron stress $(up\;to\;5\;{\mu}m\;of\;iron)$ was identified as Burkholderia sp. Hydroxamate type siderophore produced by Burkholderia sp. CAS-5 was partially purified. MMP inhibitory activity of siderophore was confirmed by gelatin zymography. The $Zn^{2+}-chelating$ activity of siderophore correlated with the inhibition of MMP-2 activity.

• BMB Reports
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• 제41권12호
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• pp.858-862
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• 2008

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent proteinase found in cholesterol-rich lipid rafts on the plasma membrane. MT1-MMP hydrolyzes extracellular matrix (ECM) proteins, activates pro-matrix metalloproteinase-2 (proMMP-2) and plays an important role in ECM remodeling, cancer cell migration and metastasis. The role of caveolin-1, an integral protein of caveolae, in the activation of MT1-MMP remains largely unknown. Here, we show that the expression of caveolin-1 attenuates the activation of proMMP-2, reduces proteolytic cleavage of ECM and inhibits cell migration. We utilized the cytoplasmic tail domain deletion (${\Delta}CT$) or the E240A mutant of MT1-MMP. Co-expression of caveolin-1 with the wild-type or the ${\Delta}CT$ MT1-MMP decreased the proMMP-2 activation and inhibited collagen degradation and cell migration. Caveolin-1 had no effect on the catalytically inert E240A MT1-MMP. Our findings suggest that caveolin-1 is essential in the down-regulation of MT1-MMP activity by promoting internalization from the cell surface.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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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.

• Biomolecules & Therapeutics
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• 제12권1호
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• pp.1-8
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• 2004

In chronic airway inflammatory diseases such as asthma and chronic bronchitis, it has been suggested that matrix metalloproteinases secreted from infiltrating neutrophil contribute the pathogenesis of the disease and have been a focus of intense investigation. We report here that hamster tracheal surface epithelial goblet cells (HTSE cells) produce matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2). Matrix metalloproteinase activities were investigated using [$^3H$]collagen-digestion assay and gelatin zymography. The subtype of matrix metalloproteinases expressed from HTSE cells was MMP-2 (gelatinase A), which was determined by Western blot with various subtype selective anti-matrix metalloproteinase antibodies. The MMP-2 and TIMP-2 cDNAs from HTSE cells were partially cloned by RT-PCR and they reveal more than 90% of sequence homology with those from human, rat and mouse. The collagenolytic activity was increased with the secretory differentiation of the HTSE cell and it was found that zymogen activation was responsible for the increased MMP-2 activity in HTSE cells. The results from the present study suggest that the metaplastic secretory differentiation of airway goblet cells may affect chronic airway inflammatory process by augmenting the zymogen activation of MMP-2.

• Animal cells and systems
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• 제10권2호
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• pp.79-83
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• 2006

Tissue plasminogen activator (tPA) is used to lyse clots and reperfuse brain in ischemic stroke. However, sideeffects of intracerebral hemorrhage (ICH) and edema limit their clinical application. In part, these phenomena has been linked with elevations in matrix metalloproteinase-9 (MMP-9) in neurovascular unit. However little is known about their regulatory signaling pathways in brain cells. Here, I examine the role of MAP kinase pathways in tPA-induced MMP-9 regulation in rat cortical astrocytes. tPA $(1-10\;{\mu}g/ml)$ induced dose-dependent elevations in MMP-9 and MMP-2 in conditioned media. Although tPA increased phosphorylation in two MAP kinases (ERK, JNK), only inhibition of the JNK pathway by the JNK inhibitor SP600126 significantly reduced MMP-9 upregulation. Neither ERK inhibition with U0126 nor p38 inhibition with SB203580 had any significant effects. Taken together, these results suggest that c-jun N-terminal kinase (JNK) plays an essential role for tPA-induced MMP-9 upregulation.

• 대한화장품학회지
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• 제42권4호
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• pp.377-385
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• 2016

본 연구에서는 참깨 추출물의 주름개선 화장품 원료로의 가능성을 확인하기 위하여, 참깨의 70% 에탄올 추출물을 제조하여, 엘라스타제 저해능, 콜라게나제 저해능, matrixmetallopoteinases (MMPs)의 단백질, mRNA 발현 저해 효능을 측정하였다. Elastase와 collagenase 저해활성은 $1000{\mu}g/mL$ 농도에서 각각 37.8%와 45%의 효소 활성을 억제를 나타내었다. 섬유아세포에서 참깨 에탄올 추출물의 세포 생존율을 확인한 결과 $100{\mu}g/mL$ 농도에서 96%의 생존율을 보였다. 참깨 에탄올 추출물을 처리한 섬유아세포에서 matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3 (MMP-3)의 단백질 발현 및 mRNA 발현 억제 효과를 확인한 결과 단백질 발현은 $100{\mu}g/mL$ 농도에서 63%, 43%, 49%의 저해율을 나타내었고, mRNA 발현 억제는 최고농도인 $100{\mu}g/mL$에서 각각 82% 79%, 82%의 저해율을 나타내었다. 이러한 결과로 보아 참깨 70% 에탄올 추출물이 주름개선용 기능성 화장품 소재로서의 응용이 가능할 것으로 판단되었다.

• 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.

• Journal of Periodontal and Implant Science
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• 제43권1호
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• pp.24-29
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• 2013

Purpose: Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, and they are inducible enzymes depending on an inflammatory environment such as periodontitis and bacterial infection in periodontal tissue. Gingival inflammation has been postulated to be correlated with the production of MMP-2 and MMP-9. The objective of this study was to quantify the expression and activity of MMP-9 and -2, and to determine the correlation between activity and expression of these MMPs in human gingival tissues with periodontitis. Methods: The gingival tissues of 13 patients were homogenized in $500{\mu}L$ of phosphate buffered saline with a protease inhibitor cocktail. The expression and activity of MMP-2 and -9 were measured by enzyme-linked immunosorbent assay and Western blot analysis, and quantified by a densitometer. For the correlation line, statistical analysis was performed using the Systat software package. Results: MMP-9 was highly expressed in all gingival tissue samples, whereas MMP-2 was underexpressed compared with MMP-9. MMP-9 activity increased together with the MMP-9 expression level, with a positive correlation (r=0.793, P=0.01). The correlation was not observed in MMP-2. Conclusions: The expression of MMP-2 and -9 might contribute to periodontal physiological and pathological processes, and the degree of MMP-9 expression and activity are predictive indicators relevant to the progression of periodontitis.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제29권4호
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• pp.212-218
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• 2003

Matrix metalloproteinases (MMPs) play an important role in the normal morphogenesis, maintenance, and repair of matrix and also have important functions in pathologic conditions characterized by excessive degradation of extracellular matrix, such as rheumatoid arthritis, osteoarthritis, periodontitis and in tumor invasion and metastasis. In this study, expression of MMP-1 and -2 mRNA in retrodiscal tissue of the temporomandibular joint (TMJ) was examined and compared with magnetic resonance imaging (MRI) and surgical findings. MMP mRNAs in the retrodiscal tissue samples were detected by reverse transcription - polymerase chain reaction. TMJ internal derangement (ID) was categorized as normal disc position, disc displacement with reduction, early stage of disc displacement without reduction (DDsR) and late stage of DDsR. TMJ osteoarthrosis (OA) was classified with normal, mild and advanced OA. The amount of synovial fluid collection was divided into not detected, small, large and extremely large amount on MR T2-weighted imaging. Perforation and adhesion were examined during open surgery of the TMJ. Six out of 37 samples were excluded because of little amount of extracted total mRNA. MMP-2 mRNA was detected whole joints, and so the MMP-2 mRNA seems to be expressed normally in retrodiscal tissue. However, MMP-1 mRNA was expressed in 8 of 31 joints. Frequencies of MMP-1 mRNA expression according to the TMJ IDs, amount of synovial fluid and surgical findings made no significant difference. MMP-1 mRNA was detected more frequently in OA groups (7/16 joints, 43.8%) than in normal bony structure group (1/15 joints, 6.7%). Expression of MMP-1 mRNA in retrodiscal tissue might be related with OA of the TMJ.