• Title/Summary/Keyword: Matrix Metalloproteinases

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The Investigation of Synovial Fluid and Serum for Biochemical Markers of Joint Diseases in the Horse (말의 활액 및 혈청 분석을 통한 관절질환의 생화학적 예측 인자)

  • 배종환;김갑수;유영춘;이회영;이경복
    • Journal of Veterinary Clinics
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    • v.18 no.3
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    • pp.304-310
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    • 2001
  • The joint disease including osteoarthris (OA) and rheumatoid arthritis (RA) are common in the horse. Many studies have been performed to develop biochemical markers reflecting the abnormalities of cartilage and synovial membrane. However, no specific, sensitive and clinically well established assay systems have been yet available to characterize the severity of joint diseases. Indeed, radiography is still doctor's best choice of assessing joint damage in OA/RA. This review focuses on biochemical molecules such as proteoglycan, collagen, matrix metalloproteinases (MMPs), lectin and cytokine to assess their potential value for not only predicting stage of joint disease but also monitoring treatment efficacy.

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Inhibitory Effect of Naringenin on MMP-2, -9 Activity and Expression in HT-1080 Cells (HT1080 세포주에서 naringenin의 MMP-2, -9 효소 활성 및 발현 억제 효과)

  • Chae, Soo-Chul
    • Environmental Analysis Health and Toxicology
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    • v.24 no.1
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    • pp.63-70
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    • 2009
  • Naringenin, major one of the citrus flavonoids, have been identified that exert antioxidative, anticancer effects. The present study investigated the effects of naringenin on tumor invasion and matrix metalloproteinases(MMPs) activities. Naringenin inhibited cell invasion of HT-1080 fibrosarcoma cells in a dose-dependent manner. The activities of MMP-2 and MMP-9 were inhibited by naringenin as demonstrated by gelatin zymography assay. Furthermore, the amounts of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed in the cells. MMP-2, MMP-9, and MT1-MMP mRNA expression were suppressed by naringenin with time and dose-dependent. These results demonstrate that anti-metastatic activities of naringenin resulted from blocking of invasion of the HT-1080 cells. Taken together, the results of this studies provide evidence that naringenin possess an anti-metastatic activity.

Antitumor effects of ophiopogonin D on oral squamous cell carcinoma

  • Nguyen Thi Kieu Trang;Vu Phuong Dong;Hoon Yoo
    • International Journal of Oral Biology
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    • v.49 no.2
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    • pp.42-47
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    • 2024
  • Ophiopogonin D (OPD) is a steroidal glycoside derived from Ophiopogon japonicus, a traditional Chinese medicine with diverse biological activities, including antithrombosis, anti-inflammation, and antitussive effects. To investigate the cellular effects and mechanisms of OPD on oral squamous cell carcinoma, cell viability was explored, and the effects of OPD on cell cycle regulators, apoptotic marker proteins, and key proteins involved in metastasis and signaling pathways were examined by MTT assay and Western blotting in YD38 cells. OPD strongly inhibited cell proliferation and induced caspase-dependent apoptosis of YD38 cells by suppressing the cell cycle and activating caspase-3 and poly ADP ribose polymerase. Additionally, OPD suppressed the expression of vital proteins regulating metastasis and proliferation within the integrin/matrix metalloproteinases/FAK and AKT/PI3K/mTor pathways. Thus, OPD can be a potential treatment candidate for gingival cancer.

Gene Expression of Metalloproteinases, Tissue Inhibitors of Metalloproteinases and Cytokines in Adriamycin-induced Cardiomyopathy (아드리아마이신으로 유도된 심근증에서 Metalloproteinase, Metalloproteinase 조직억제자, Cytokine 유전자 발현에 대한 연구)

  • Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.48 no.2
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    • pp.197-203
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    • 2005
  • Purpose : Changes in metalloproteinases(MMP) activity have been demonstrated in several disease states, including rheumatoid arthritis and tumor metastasis. More importantly, increased myocardial MMP activity has been reported to occur in both clinical and experimental forms of dilated cardiomyopathy. There was no report about MMP in adriamycin(ADR)-induced cardiomyopathy. The purpose of this study was to investigate gene expression of MMP and tissue inhibitor of metalloproteinases(TIMP) in ADR-induced cardiomyopathy and clarify the relationship between MMP and cytokines. Methods : Male Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injections of ADR(5 mg/kg) twice a week over two weeks. Serum concentrations of MMP, TIMP, interleukin(IL)-6 and tumor necrosis factor(TNF)-${\alpha}$ were measured. RNA extraction was performed from frozen rat hearts. Reverse transcription polymerase chain reaction(RT-PCR) was employed. cDNA Microarray analysis was performed by using a set of 5,184 sequence-verified rat cDNA clones. Results : Serum MMP and TIMP levels were not significantly different between the two groups. IL-6 was $36.8{\pm}2.8pg/mL$ and TNF-${\alpha}$ $2.2{\pm}2.7pg/mL$ in the ADR group. They were significantly higher than in the control group. Serum MMP correlated significantly with TNF-${\alpha}$(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-${\alpha}$ in the hearts of both groups. Gene expression of TIMP was significantly depressed in the hearts of the ADR group. Conclusion : These results suggested a potential role for TNF-${\alpha}$ in the regulation of extracellular matrix remodeling in ADR induced cardiomyopathy. Rapid screening of multiple decreased gene expression by DNA chip may be a useful diagnostic test to detect early cardiac injury before developing ADR induced cardiomyopathy.

Comparison of Antioxidant and Matrix Metalloproteinases Inhibitory Effects of Sorbus commixta Twig Extracts before and after Fermentation with Lactobacillus pentosus (Lactobacillus pentosus에 의한 발효 전후 마가목 가지 추출물의 항산화 활성 및 Matrix Metalloproteinases 발현 억제 효과)

  • Park, Young Min;Park, So Hyun;Cha, Mi Yeon;Kang, Hee Cheol;Park, Soo Nam
    • Applied Chemistry for Engineering
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    • v.28 no.6
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    • pp.696-704
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    • 2017
  • In this study, we investigated antioxidative and matrix metalloproteinases (MMPs) inhibitory effects of Sorbus commixta twig extracts and fermented extracts with Lactobacillus pentosus and analyzed active ingredients. The free radical scavenging activity ($FSC_{50}$) of non-fermented and fermented extracts of S. commixta twig' were 41.04 and $58.2{\mu}g/mL$, respectively. In the $Fe^{3+}-EDTA/H_2O_2$ system, the active oxygen scavenging activity ($OSC_{50}$) was 2.6 and $3.0{\mu}g/mL$, respectively. In the dermal fibroblasts, the intracellular reactive oxygen species (ROS) scavenging activity was 35.3% for non-fermented extract and 40.2% for fermented extracts at the concentration of $10{\mu}g/mL$. Also at the same concentration, the expression of MMPs (MMP-1, -2, -3) by western blot was 68.3, 35.0 and 24.2%, respectively for non-fermented extracts and 84.3, 70.5 and 69.2% for fermented extracts. TLC, HPLC, and LC/ESI-MS/MS were used for measuring the changes in the components of the extract before and after fermentation. As a result, caffeic acid, (-)-epicatechin, isoquercitrin, and quercetin were identified. From the results, S. commixta twig fermented extracts by L. pentosus showed greater ROS scavenging activity and inhibitory effects on MMPs expression than those of using non-fermented extracts. Therefore, it is suggested that S. commixta twig fermented extracts can be used as an anti-aging cosmetic material.

Effect of Soybean Fallen Leaves Ethanolic Extract on Expression of Proteins Related to Antioxidant Activity and Cell Invasion (항산화 및 암전이 관련 단백질의 발현에 미치는 콩잎낙엽 에탄올 추출물의 영향)

  • Song, Chaeeun;Lee, Su-Gyeong;Hong, Sugyeong;Ryu, Zoon Ha;Kim, Moon-Moo;Oh, Yunghee
    • Journal of Life Science
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    • v.26 no.4
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    • pp.439-445
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    • 2016
  • Soybean leaves, a Korean edible plant material, have been reported to prevent the development of osteoporosis and breast cancer. Based on this rational, soybean fallen leaves ethanolic extract (SBFL) was used for the experiment of cell invasion related to metastasis and antioxidant activity. The effect of SBFL on matrix metalloproteinases (MMPs) in human fibrosarcoma cells, HT1080 as well as its anti-oxidant activity was investigated in this study. The effect of SBFL on scavenging activity of reactive oxygen species was evaluated in vitro using lipid peroxidation assay,DPPH radical and reducing power assay. SBFL showed the positive effects on antioxidant activity, compared with vitamin C and vitamin E used as positive controls. Furthermore, SBFL showed cytotoxicity above 16 µg/ml in MTT assay. In particular, it was found that SBFL decreased the activation of MMP-9 stimulated by phorbol 12-myristate 13-acetae (PMA) and phenazine methosulfate (PMS). SBFL treatment increased the expression levels of p-FoxO-1 and SOD-1. Moreover, SBFL inhibited cell invasion stimulated by vascular endothelial growth Factor (VEGF). These results indicate that SBFL could inhibit cell invasion related to the activation of MMP-9 and oxidative stress, suggesting that it could be available as a main ingredient for prevention of metastasis.

The Effects of HangAmDan(HAD) on Anti-Metastasis and Preventing Relapses, Administered to 69 Cancer Patients (각종 암환자 69례에 대한 항암단의 항전이 및 재발억제효과)

  • Lee, Yong-Yeon;Song, Kee-Cheol;Choi, Byung-Lyul;Seo, Sang-Hoon;Cho, Jung-Hyo;Lee, Yeon-Weol;Son, Chang-Gue;Cho, Chong-Kwan;Yoo, Hwa-Seung
    • The Journal of Internal Korean Medicine
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    • v.23 no.2
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    • pp.165-173
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    • 2002
  • Purpose : Among numerous biological symptoms of cancer, matrix metalloproteinases (MMPs) are essential for tumor invasion and metastasis. HAD is used as an inhibitor of MMP gene. This study was designed to evaluate the effects of HAD on anti metastasis and preventing recurrence in cancer patients. Materials and Methods : We retrospectively analyzed the medical records of 69 cancer patients who had been administered with HAD for over 12 months continuously in East-West Cancer Center of Oriental Hospital of Daejeon University, from January 1993 to May 2002. Results : We analyzed gender, portion, stage and anti-metastasis & recurrence rates of cancer patients. Analysis of sex cases showed that the percentage of male is 62.3%, female is 37.7%. Analysis of cancer portion showed that the percentage of stomach is 31.9%, colorectum is 26.1%, lung is 21.7%, liver is 8.7%, breast is 8.7% Analysis of stage showed that the rate of III is 78.3%, IV is 13.0% and II is 8.7%. Analysis of anti-metastasis and recurrence rates showed that colorectal cancer is 77.8%, stomach cancer is 63.6%, lung cancer is 33.4% and breast cancer is 33.3% (mean : 53.6%). Conclusions : HAD has significant effects on anti-metastasis and preventing recurrence of tumor on cancer patients. So it helps to prolong the survival rates of cancer patients.

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Metallothinein 1E Enhances Glioma Invasion through Modulation Matrix Metalloproteinases-2 and 9 in U87MG Mouse Brain Tumor Model

  • Hur, Hyuk;Ryu, Hyang-Hwa;Li, Chun-Hao;Kim, In Young;Jang, Woo-Youl;Jung, Shin
    • Journal of Korean Neurosurgical Society
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    • v.59 no.6
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    • pp.551-558
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    • 2016
  • Malignant glioma cells invading surrounding normal brain are inoperable and resistant to radio- and chemotherapy, and eventually lead to tumor regrowth. Identification of genes related to motility is important for understanding the molecular biological behavior of invasive gliomas. According to our previous studies, Metallothionein 1E (MT1E) was identified to enhance migration of human malignant glioma cells. The purpose of this study was to confirm that MT1E could modulate glioma invasion in vivo. Firstly we established 2 cell lines; MTS23, overexpressed by MT1E complementary DNA construct and pV12 as control. The expression of matrix metalloproteinases (MMP)-2, -9 and a disintegrin and metalloproteinase 17 were increased in MTS23 compared with pV12. Furthermore it was confirmed that MT1E could modulate MMPs secretion and translocation of NFkB p50 and B-cell lymphoma-3 through small interfering ribonucleic acid knocked U87MG cells. Then MTS23 and pV12 were injected into intracranial region of 5 week old male nude mouse. After 4 weeks, for brain tissues of these two groups, histological analysis, and immunohistochemical stain of MMP-2, 9 and Nestin were performed. As results, the group injected with MTS23 showed irregular margin and tumor cells infiltrating the surrounding normal brain, while that of pV12 (control) had round and clear margin. And regrowth of tumor cells in MTS23 group was observed in another site apart from tumor cell inoculation. MT1E could enhance tumor proliferation and invasion of malignant glioma through regulation of activation and expression of MMPs.

Anti-wrinkle effect of berberine by inhibition of MMP-2 and MMP-9 activity in fibroblasts (섬유아세포에서의 MMP-2 및 MMP-9 활성 억제에 의한 베르베린의 항주름 효과)

  • Jang, Young-Ah;Lee, Jin-Tae
    • Journal of Applied Biological Chemistry
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    • v.61 no.1
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    • pp.9-15
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    • 2018
  • We analyzed the antioxidant and anti-wrinkle activities of berberine, isolated from dried rhizome of Coptis japonica Makino, to determine its cosmetic potential. We performed the 3-[4,5-dimethylthiazol]-2-yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay to evaluate the toxicity of the berberine. We also measured the ROS and hyaluronic acid production, and expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and tumor necrosis factor-alpha ($TNF-{\alpha}$) to evaluate the antioxidant and anti-wrinkle activities of berberine, respectively. The cytotoxicity of ultraviolet light, in presence of berberine, was measured by the MTT assay using CCD-986sk fibroblasts, and no cytotoxicity was observed at concentrations less than $25{\mu}g/mL$. We also found that berberine decreased ROS production in a concentration-dependent manner and promoted the synthesis of hyaluronic acid. Further, berberine reduced the protein levels and mRNA expression of MMP-2 and MMP-9, which are associated with wrinkle formation, and increased the expression of TIMP-1 and TIMP-2. In addition, the inhibitory effect of berberine on $TNF-{\alpha}$, known as pro-inflammatory cytokine, was inhibited by $TNF-{\alpha}$ gene in a concentration-dependent manner. These results suggest that berberine holds cosmetic value owing to its antioxidant activity, by inhibiting ROS production and anti-wrinkle activity by reducing MMP-2 and MMP-9 and increasing TIMP-1 and TIMP-2 expression.

Collagen synthesis ability and inhibitory effect of MMPs in keratinocytes of Lysimachia christinae Hance Extract (금전초 추출물의 케라티노사이트 내 collagen 합성능 및 MMPs 억제효과)

  • Kim, Ju-Eun;Choi, Yun-Sik;Kim, Hye Kyung;Jang, Young-Ah
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.4
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    • pp.820-829
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    • 2020
  • This study was conducted to investigate the anti-oxydant and anti-winkle efficacy as cosmetics ingredient of Lysimachia christinae Hance. Recently, the study of wrinkle improvement of natural products has received continuous interest. so we looked at relationship between reactive oxygen species (ROS) generation and pro-collagen synthesis and matrix metalloproteinases (MMPs) through this study. L. christinae Hance were extracted with 70% ethanol (LcHE) and distilled water (LcHW), respectively, and the experiment was conducted. LcHE had better ROS inhibition effect than LcHW and showed no toxicity up to 250 ㎍/mL concentration as a result of MTT assay in HaCaT cells, so we selected LcHE and conducted the wrinkle improvement material study. We confirmed that the synthesis of type-1 pro-collagen reduced by UVB is activated through pro-collagen synthesis assay. we confirmed that LcHE inhibited the increase in MMP-1 -3 -9 of MMPs induced by UVB in skin cells through western blot and we also performed real-time PCR to confirm the effect of the extract with dependence of concentration at mRNA levels. Therefore, it is expected that Lysimachia christinae Hance is used as a natural material for cosmetics that can effectively prevent wrinkles and skin aging by UVB.