• 제목/요약/키워드: Matrix Metalloproteinases

검색결과 333건 처리시간 0.03초

구강 편평 상피 암종에서 TGF-${\beta}1$과 MMP-2의 발현과 경부 임파절 전이 간의 상관 관계에 관한 연구 (THE CLINICAL SIGNIFICANCE OF THE EXPRESSION OF TGF-${\beta}1$ AND MMP-2 RELATED TO THE REGIONAL LYMPH NODE METASTASIS IN THE ORAL SQUAMOUS CELL CARCINOMA)

  • 김좌영;;김성곤
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제33권3호
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    • pp.199-203
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    • 2007
  • Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (OSCC). The members of the TGF-$\beta$ signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis and molecular targets for the prevention and the treatment of cancer and metastasis. The aim of the present study was to find the clinical significance of the expression of TGF-${\beta}1$ and MMP-2 related to the regional lymph node metastasis in OSCC. This study included 76 cases of primary OSCC, of which 42 cases showed regional lymph node metastases. Immunohistochemistry was used for the localization of protein. The relation between the expression of each protein and clinical variables was statistically evaluated. In results, the expression of TGF-${\beta}1$ both main mass with lymph node metastasis and without lymph node metastasis was found not to be statistically significant (p>0.05). The expression of MMP-2 was found to be statistically significant related to regional lymph node metastasis (p<0.05). When compared the expression in the metastatic lymph node, TGF-${\beta}1$ was significantly highly expressed than MMP-2 (p<0.05). In conclusion, the expression of MMP-2 was significantly elevated in patients with lymph node metastasis as compared to the patients without lymph node metastasis, which could be useful in predicting the risk of lymph node metastasis in OSCC.

PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model

  • Hwang, Hyun Sook;Park, In Young;Kim, Dae Won;Choi, Soo Young;Jung, Young Ok;Kim, Hyun Ah
    • BMB Reports
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    • 제48권7호
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    • pp.407-412
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    • 2015
  • The 12 kDa FK506-binding protein (FK506BP12), an immunosuppressor, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13 in addition to cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression. [BMB Reports 2015; 48(7): 407-412]

The influence of type 2 diabetes mellitus on the expression of inflammatory mediators and tissue inhibitor of metalloproteinases-2 in human chronic periodontitis

  • Kim, Jae-Bung;Jung, Mi-Hwa;Cho, Je-Yeol;Park, Jin-Woo;Suh, Jo-Young;Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • 제41권3호
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    • pp.109-116
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    • 2011
  • Purpose: The purpose of this study was to compare and quantify the expression of C-reactive protein (CRP), matrix metalloproteinase (MMP)-14, and tissue inhibitor of metalioproteinases (TIMP)-2 in gingival tissues of patients with chronic periodontitis accompanied with inflammatory reaction related to alveolar bone resorption with or without type 2 diabetes mellitus (DM). Methods: Twelve patients with type 2 DM and chronic periodontitis (group 3), twelve patients with chronic periodontitis (group 2), and twelve healthy individuals (group 1) were included in the study. Gingival tissue biopsies were collected from each patient and from healthy individuals at the time of periodontal surgery (including surgical crown lengthening) or tooth extraction. The concentrations of cytokines were determined by a western blot analysis. Results: The expression levels of CRP and MMP-14 increased in group 2 and 3, and they were highest in group 3. The expressions of TIMP-2 also increased in group 2 and 3. Conclusions: This study demonstrated that the expression levels of CRP, MMP-14, and TIMP-2 might be inflammatory markers in periodontal inflamed tissue. It can be assumed that CRP, MMP-14, and TIMP-2 may be partly involved in the progression of periodontal inflammation associated to type 2 DM.

대영전의 Monosodium Iodoacetate 유발 관절연골손상 억제 효과 (Inhibitory Effects of Daeyeoungjeon on the Injury of Articular Cartilage Induced by Monosodium Iodoacetate in Rats)

  • 서일복;정수현;박동수
    • 한방재활의학과학회지
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    • 제27권2호
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    • pp.9-17
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    • 2017
  • Objectives This study was aimed to evaluate the effects of Daeyoungjeon (hereinafter referred to DYJ) treatment on the injury of articular cartilage induced by monosodium iodoacetate in rats. Methods Twenty-four male rats were divided into normal, osteoarthritic control and DYJ group. Rats of normal group were injected with 0.1 ml physiological saline, rats of control and DYJ groups were injected with 0.1 ml monosodium iodoacetate (3 mg/ml) into each left and right knee joint cavities. Rats of DYJ group were administrated extracts of DYJ during 60 days per orally. At 60 days after treatment, gross lesions, area and proteoglycan contents of articular cartilage, histopathological lesions, immunohistochemistry on matrix metalloproteinases (MMP-2, MMP-3, MMP-7) were evaluated. Results Grossly, degenerative changes of articular cartilages were observed weak in DYJ group. The areas of articular cartilages were broader significantly in DYJ group. The proteoglycan contents in articular cartilages were lesser significantly in DYJ group. Histopathologically, the chondrocyte score was lesser significantly in DYJ group. MMP-3 expression in articular cartilages was observed weak in DYJ group. Conclusions From above results, DYJ treatment has inhibitory effects on the injuries of articular cartilage induced by monosodium iodoacetate in rats, and it's effects may be related with down regulation of MMP-3.

Evaluation of Effective MMP Inhibitors from Eight Different Brown Algae in Human Fibrosarcoma HT1080 Cells

  • Bae, Min Joo;Karadeniz, Fatih;Ahn, Byul-Nim;Kong, Chang-Suk
    • Preventive Nutrition and Food Science
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    • 제20권3호
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    • pp.153-161
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    • 2015
  • Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that have important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Marine plants are on the rise for their potential to provide natural products that exhibit remarkable health benefits. In this context, brown algae species have been of much interest in the pharmaceutical field with reported instances of isolation of bioactive compounds against tumor growth and MMP activity. In this study, eight different brown algae species were harvested, and their extracts were compared in regard to their anti-MMP effects. According to gelatin zymography results, Ecklonia cava, Ecklonia bicyclis, and Ishige okamurae showed higher inhibitory effects than the other samples on MMP-2 and -9 activity at the concentrations of 10, 50, and $100{\mu}g/mL$. However, only I. okamurae was able to regulate the MMP activity through the expression of MMP and tissue inhibitor of MMP observed by mRNA levels. Overall, brown algae species showed to be good sources for anti-MMP agents, while I. okamurae needs to be further studied for its potential to yield pharmaceutical molecules that can regulate MMP-activity through cellular pathways as well as enzymatic inhibition.

Estrogen-related receptor γ is a novel catabolic regulator of osteoarthritis pathogenesis

  • Son, Young-Ok;Chun, Jang-Soo
    • BMB Reports
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    • 제51권4호
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    • pp.165-166
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    • 2018
  • Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability with a large socioeconomic cost. OA is a whole-joint disease characterized by cartilage destruction, synovial inflammation, osteophyte formation, and subchondral bone sclerosis. To date, however, no effective disease-modifying therapies for OA have been developed. The estrogen-related receptors (ERRs), a family of orphan nuclear receptor transcription factors, are composed of $ERR{\alpha}$, $ERR{\beta}$, and $ERR{\gamma}$, which play diverse biological functions such as cellular energy metabolism. However, the role of ERRs in OA pathogenesis has not been studied yet. Among the ERR family members, $ERR{\gamma}$ is markedly upregulated in human and various models of mouse OA cartilage. Adenovirus-mediated overexpression of $ERR{\gamma}$ in the mouse knee joint tissue caused OA pathogenesis. Additionally, cartilage-specific $ERR{\gamma}$ transgenic (Tg) mice exhibited enhanced experimental OA. Consistently, $ERR{\gamma}$ in articular chondrocytes directly caused expression of matrix metalloproteinase (MMP) 3 and MMP13, which play a crucial role in cartilage destruction. In contrast, genetic ablation of Esrrg or shRNA-mediated Esrrg silencing in the joint tissues abrogated experimental OA in mice. These results collectively indicated that $ERR{\gamma}$ is a novel catabolic regulator of OA pathogenesis and can be used as a therapeutic target for OA.

The Processed Radish Extract Melanogenesis in Humans and Induces Anti-Photoaging Effects in Ultraviolet B-Induced Hairless Mouse Model

  • Kim, Hyun-Kyoung
    • International Journal of Advanced Culture Technology
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    • 제7권4호
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    • pp.125-136
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    • 2019
  • The radish skin and radish greens are an edible part of the radish. But they are removed before eating the radish and used as a byproduct or an animal feed material because of their tough and rough texture. Melanin is a pigment that gives colour to our skin. But increased production of melanin can turn into benign or malignant tumours. These days due to global warming, the amount of Ultra violet (UVB) rays has been extensively increased with sunlight. Due to this, a phenomenon called exogenous photo aging is widely observed for all skin colour and types. As a result of this phenomenon, a set of enzymes called matrix metalloproteinases (MMP's) that serves as degradation enzymes for extracellular matrix proteins mainly collagen is increased, causing depletion in collagen and resulting in early wrinkles formation. Therefore in our study we used the murine melanoma cell line B16/F10 to study the melanogenesis inhibition by Heated radish extract (HRE) in vitro and we used HRM-2 hair less mice exposed to artificial UVB for checking the efficacy of Heated radish extract in vivo. Furthermore, we prepared a 3% Heated radish extract (HRE) cream and checked its effects on human skin. Our results have clearly demonstrated that Heated radish extract (HRE) have potently suppressed the tyrosinase activity and melanin production in B16/F10 cells. It had also reduced the expression of components involved in melanin production pathway both transcriptionally and transitionally. In in vivo studies, HRE had potently suppressed the expression of MMP's and reduced the wrinkle formation and inhibited collagen degradation. Moreover, on human skin, ginseng cream increased the resilience, skin moisture and enhanced the skin tone. Therefore in light of these findings, we conclude that HRE is an excellent skin whitening and antiaging product.

사멸세포에서의 metalloproteinase-9의 작용 (Up-regulation of Matrix Metalloproteinase-9 in Smooth Muscle Cell Undergoing Death)

  • 이경아;김선미;김관회
    • 생명과학회지
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    • 제16권7호
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    • pp.1229-1234
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    • 2006
  • 배지에 tetracycline이 없으면 사멸하는 평활근세포 (FADD-SMC)를 이용하여 metalloproteinase (MMP)와 사멸세포의 상관관계를 조사하였다. FADD-SMC를 tetracycline이 없는 배지에서 배양하는 경우 핵이 조각으로 잘라졌고 인산화한 p38과 ERK가 증가하고 MMP-9의 발현과 활성이 증가한 반면, cyclin D와 cyclin D의 발현은 감소하였다. 그리고 죽는 FADD-SMC에서 MMP-9의 발현은 immunofluorescen로 재확인하였다. MMP-9의 증가는 MAPK 억제제인 PD098059와 p38 MAPK 억제제인 SB203S80에 의하여 감소하였다. 그리고 MMP 억제제인 BB94는 FADD-SMC의 사멸을 감소시켰다.

Characterization of H460R, a Radioresistant Human Lung Cancer Cell Line, and Involvement of Syntrophin Beta 2 (SNTB2) in Radioresistance

  • Im, Chang-Nim;Kim, Byeong Mo;Moon, Eun-Yi;Hong, Da-Won;Park, Joung Whan;Hong, Sung Hee
    • Genomics & Informatics
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    • 제11권4호
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    • pp.245-253
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    • 2013
  • A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and ${\gamma}$-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy.

Blockade of vascular angiogenesis by Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujuba

  • Kang, Sang-Wook;Choi, Jung-Suk;Bae, Ji-Young;Li, Jing;Kim, Dong-Shoo;Kim, Jung-Lye;Shin, Seung-Yong;You, Hyun-Ju;Park, Hyoung-Sook;Ji, Geun-Eog;Kang, Young-Hee
    • Nutrition Research and Practice
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    • 제3권1호
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    • pp.3-8
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    • 2009
  • The matrix metalloproteinases (MMP) play an important role in tumor invasion, angiogenesis and inflammatory tissue destruction. Increased expression of MMP was observed in benign tissue hyperplasia and in atherosclerotic lesions. Invasive cancer cells utilize MMP to degrade the extracellular matrix and vascular basement membrane during metastasis, where MMP-2 has been implicated in the development and dissemination of malignancies. The present study attempted to examine the antiangiogenic activity of the medicinal herbs of Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujube (tAgR and tZj) with respect to MMP-2 production and endothelial motility in phorbol 12-myristate 13-acetate (PMA)- or VEGF-exposed human umbilical vein endothelial cells (HUVEC). Nontoxic tAgR and tZj substantially suppressed PMA-induced MMP-2 secretion. In addition, $25{\mu}g/mL$ tAgR and tZj prevented vascular endothelial growth factor-stimulated endothelial cell transmigration and tube formation. The results reveal that tAgR and tZj dampened endothelial MMP-2 production leading to endothelial transmigration and tube formation. tAgR and tZj-mediated inhibition of endothelial MMP may boost a therapeutic efficacy during vascular angiogenesis.