• Title/Summary/Keyword: Matrix Metalloproteinase

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Study on the Expression of Matrix Metalloproteinase-1 by Promoter Polymorphism in Human Dermal Fibroblast (섬유아세포에서 프로모터 다형성에 의한 Matrix Metalloproteinase-1의 발현에 관한 연구)

  • Lee, Jin Woo;Jung, Yujung;Bong, Sim-Kyu;Park, No-June;Lee, Sang Heon;Noh, Minsoo;Lim, Kyung-Min;Kim, Su-Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.47 no.3
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    • pp.205-212
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    • 2021
  • The skin fibroblasts of different origins showed different expression levels of MMP-1 in response to TNF-α treatment or UV irradiation. We hypothesized that this is caused by polymorphism in the MMP-1 promoter region. To elucidate it, first of all, we analyzed and classified the genotype of the -1607 site of the MMP-1 promoter in 23 commercially available primary fibroblasts, and then we examined the expression of MMP-1 by TNF-α or UVB stimulation for each classified genotype. As a result of the analysis, fibroblasts with 6 1G/1G genotypes, 10 1G/2G genotypes, and 7 2G/2G genotypes were identified. Hs68 and Detroit 551 cell lines were confirmed to have 1G/2G genotypes. In the 1G/1G genotype, MMP-1 was expressed twice as high as that of the control group by TNF-α treatment, and was hardly expressed by UV light. In the case of the 1G/2G genotype, MMP-1 was expressed 2.45 fold higher by TNF-α treatment, and 1.4 fold by UV light than the control. In the case of the 2G/2G genotype, MMP-1 was expressed 1.35 fold by TNF-α treatment, and was highly expressed by 2.5 fold by ultraviolet rays compared to control. It can be estimated that MMP-1 expression is better induced in the 1G genotype by TNF-α and in the 2G genotype by UV light. In addition, it can be presumed that MMP-1 expression is increased by creating a site where the Ets transcription factor can bind by another G inserted at the -1607 position. These studies have not been conducted at all in fibroblasts in relation to skin aging, so it is an area that needs to be further studied in the future. In conclusion, since the skin is an organ that is affected by both intrinsic aging and photoaging at the same time, when analyzing the expression of MMP-1 as a target for improving skin aging, it is necessary to select cells with a genotype suitable for the experimental conditions of the study.

Mechanisms of Korean red ginseng and herb extracts(KTNG0345) for anti-wrinkle activity (홍삼 생약 복합물(KTNG0345)의 피부 주름개선에 관한 작용기전)

  • So, Seung-Ho;Lee, Seong-Kye;Hwang, Eui-Il;Koo, Bon-Suk;Han, Gyeong-Ho;Chung, Jin-Ho;Lee, Min-Jung;Kim, Na-Mi
    • Journal of Ginseng Research
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    • v.32 no.1
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    • pp.39-47
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    • 2008
  • UV irradiation causes skin-aging involving coarse wrinkles, thickening, dyspigmentation, and rough skin surface. These phenomena in complex skin tissue is controlled with receptor of cell surface growth factor and cytokine receptors. The activation of receptors induces multiple downstream signaling pathways including expression of MMPs (matrix metalloproteinases). This study was aimed to elucidate the mechanism for anti-wrinkle activity of Korean red ginseng, Torilis fructus and Corni fructus mixture (KTNG0345). In this animal study, we have investigated decreasing effects of Korean red ginseng mixture on MMP-3 synthesis through diminishing $TNF-{\alpha}$ signaling that express MMP-1, -3, and -9. c-Jun and c-fos as a component of transcription factor AP-1 (activator protein-1) were analyzed the expression level using real time PCR and western blotting. c-Jun was decreased dose dependent manner both gene and protein level where as cfos was not changed. In upstream, JNK and PAK was not changed, but p38 was decreased in down stream. MMP-3, final product in this pathway was significantly decreased in dose dependent manner. These results suggest that Korean red ginseng mixture have a anti-wrinkle activity through $TNF-{\alpha}$ mediated MMPs expression pathway.

Oral Administration of KTNG0345 Prepared from Red Ginseng Extracts Reduces UVB-induced Skin Wrinkle Formation in Hairless Mice

  • Lee, Min-Jung;Won, Chong-Hyun;Lee, Se-Rah;Kim, Ji-Sook;Oh, Inn-Gyung;Hwang, Eui-Il;Kim, Na-mi;Kang, Byeong-Choel;Chung, Jin-Ho
    • Journal of Ginseng Research
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    • v.32 no.1
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    • pp.48-56
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    • 2008
  • Chronic ultraviolet (UV) exposure is the major cause of photoaging that causes skin wrinkling, roughness, dryness, laxity, and pigmentation. Recently, increasing efforts are being made to understand the relationship between foods and skin health. Ginsenosides are present in ginseng (Ginseng Radix Rubra) extract, and are known to have biomedical properties, such as, anti-oxidant and anti-inflammatory effects. In this study, we investigated whether KTNG0345 prepared from red ginseng extracts delivered orally reduces skin wrinkling and ultraviolet B (UVB)-induced wrinkle formation in hairless mouse skin. KTNG0345 was administrated orally to the mice (5 times a week) during the period of UVB-irradiation (3 times a week) for 8 weeks at three different doses of 300 mg/kg, 500 mg/kg and 1000 mg/kg (w/v). UV doses were increased weekly by 1 MED (1MED = 75 $mJ/cm^2)$ up to 4 MED and then maintained at this level. After the 8-week administration period, it was found that orally administered KTNG0345 significantly inhibited UVB-induced wrinkle formation in a dose-dependent manner. Increases in skin thickness caused by UVB were prevented by KTNG0345. Moreover, it also significantly inhibited matrix metalloproteinases (MMP) -13 and MMP-9 expressional inductions by UVB. In addition, KTNG0345 was observed to prevent UVB-induced water loss of epidermis in hairless mouse skin. Our results demonstrate that orally administered KTNG0345 has anti-wrinkling effects in hairless mouse skin, and suggest that dietary red ginseng and herbal mixture may be considered a functional beauty food for preventing UVB-induced skin wrinkles.

Effects of Porphyromonas gingivalis extracts on the function of mouse calvarial primary osteoblastic cells (Porphyromonas gingivalis 추출물이 마우스 두개골 일차 조골세포의 기능에 미치는 효과)

  • Yun, Jeong-Ho;Choi, Seong-Ho;Cho, Kyoo-Sung;Chai, Jung-Kiu;Kim, Chong-Kwan;Kim, Chang-Sung
    • Journal of Periodontal and Implant Science
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    • v.33 no.4
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    • pp.585-597
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    • 2003
  • Porphyromonas gingivalis has been implicated as an important periodontophathic bacterium in the etiology and progression of periodontal diseases. It has been reported that P.gingivalis may mediate periodontal destruction not only directly through its virulence factors, but also indirectly by including complex host mediated inflammatory reponses. The purpose of this study was t o evaluate the effects of P.gingivalis on the bone formation and resorption by osteoblasts. For this purpose, after determining the concentration below which sonicated P.gingivalis extracts (SPEs) have no cytotoxicity on mouse calvarial primary osteoblastic (POB) cells, we investigated the effects of SPEs on the alkaline phosphatase (ALP) activity, matrix metalloproteinase (MMP) expression (MMP-2, -9, 13), and prostaglandin $E_2$ ($PGE_2$) release in POB cells by treatment with SPEs below that concentration. The results were as follows; 1. SPEs showed no cytotoxic effect on POB cells up to a concentration of 1 ${\mu}m$/ml. 2. The treatment with SPEs reduced ALP activity in a dose-dependent manner in POB cells, In addition, when we investigated the effect of SPEs (1 ${\mu}m$/ml) on ALP activity for different exposure periods, statistically significant inhibition of ALP activity was shown at 2 days of exposure, and further significant inhibition occurred by extending the periods of exposure. 3. The treatment with SPEs stimulated the gene expression of MMP-9 in POB cells. 4. The pre-treatment with SPEs increased the amount of $PGE_2$ released in POB cells. In summary, the present study shows that P.gingivalis could inhibit osteogenesis and stimulate bone resorption not only by reducing ALP activity but also by increasing MMP-9 mRNA expression in osteoblasts, possibly through an endogenous $PGE_2$ pathway. In addition, our results suggest that if P.gingivalis affects osteoblasts in early differentiation stage, such effects by P. gingivalis could be irreversible.

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.

Antioxidant and Antiaging Effect of Ginseng Berry Extract Fermented by Lactic Acid Bacteria (유산균 발효에 의한 인삼열매 추출물의 항산화 및 항노화 효과)

  • Jeon, Ji-Min;Choi, Sung-Kyu;Kim, Yun-Jeong;Jang, Su-Jin;Cheon, Jong-Woo;Lee, Hyun-Sang
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.37 no.1
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    • pp.75-81
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    • 2011
  • The effect of lactic acid bacteria.fermented ginseng berry extract (FGBE) on physiological activities was evaluated. The contents of ginsenosides Re, Rc, and Rb1 in ginseng berry extract (GBE) were increased after fermentation by lactic acid bacteria when analyzed by high performance liquid chromatography. Antioxidant activity of GBE and FGBE was also analyzed by DPPH radical scavenging activity assay and SOD.like activity assay. FGBE showed a 86.34 % inhibition of DPPH radical and a 76.82 % inhibition by SOD.like activity at a concentration of 1.00 %. GBE showed a 49.78 % inhibition of DPPH radical and a 40.80 % inhibition by SOD.like activity at the same concentration. Furthermore, procollagen type I (COL1A1) gene expression increased by 823.13 % and matrix metal-loproteinase(MMP)-1 and tumor necrosis factor (TNF)-${\alpha}$ gene expression decreased by 87.88 % and 99.92 %, respectively, in human fibroblast cultured with FGBE at a concentration of 0.50 %. These results suggest that FGBE could be used as an active ingredient for functional cosmetics.

Effect of Phellinus Extracts on Sprouting in Porcine Pulmonary Artery Endothelial Cells (혈관내피세포의 발아에 미치는 상황버섯 추출물의 효과)

  • Oh, In-Suk;Kim, Hwan-Gyu
    • KSBB Journal
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    • v.21 no.4
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    • pp.292-297
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    • 2006
  • One of the steps in angiogenesis is the degradation of the underlying basement membrane via proteases. Endothelial cells release proteinases to degrade the extracellular matrix for their sprouting in vivo. In this study, we examined the effect of water extracts of Phellinus linteusis(Phellinus extracts) and combination of Phellinus extracts and fibroblast growth factor(FGF-2) on cultured porcine pulmonary artery endothelial cells(PPAECs). Phellinus extracts induced sprouting of PPAECs, which was inhibited by MMPs and plasmin inhibitors, and induced the secretion of matrix metalloproteinase-3(MMP-3) and plasmin. At high concentration of Phellinus extracts($200{\sim}400{\mu}g/mL$), the active MMP-2 secretion was induced. It is therefore, suggested that Phellinus extracts induces the sprouting of cultured endothelial cells by means of increased active MMP-2 and plasmin secretion. Also, combination with Phellinus extracts and FGF-2 produced an enhanced effect on sprouting and secretion of active MMP-2, and MMP-3 and plasmin from PPAECs.

Anti-osteoarthritis effects of Pomegranate, Eucommiae cortex and Achyranthis radix extracts on the primary cultured rat articular chondrocytes

  • Choi, Beom-Rak;Ku, Sae-Kwang;Kang, Su-Jin;Park, Hye-Rim;Sung, Mi-Sun;Lee, Young-Joon;Park, Ki-Moon
    • Journal of Society of Preventive Korean Medicine
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    • v.21 no.3
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    • pp.87-98
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    • 2017
  • Objectives : The objective of present study is to evaluate anti-arthritic effects of dried pomegranate concentrate powders (PCP), Eucommiae Cortex aqueous (EC) and ethanolic (ECe) extracts, Achyranthis Radix aqueous (AR) and ethanolic (ARe) extracts on the primary cultured rat articular chondrocytes. Methods : MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium Bromide) assay was performed cytotoxic effect of test substances. In addition, anti-inflammatory effects were also observed on the lipopolysaccaride (LPS) treated chondrocytes through prostaglandin $E_2\;(PGE_2)$ production and 5-lipoxygenase (LPO) activities, and inhibitory effects on metalloproteinase (MMP)-2 and MMP-9 activities were observed on the recombinant human interleukin $(rhIL)-1{\alpha}$ treated chondrocytes with their extracellular matrix (ECM) related mRNA expressions - collagen type II, SOX9 and aggrecan. Results : As results, ECe and ARe showed obvious cytotoxicity against primary cultured rat articular chondrocytes at a dose level of 10 mg/ml, respectively. However, no obvious cytotoxic effects of PCP, EC and AR were demonstrated at a dose level of 10 mg/ml, on the primary cultured rat articular chondrocytes. In addition, treatment of LPS $50{\mu}g/ml$ induced significant increases of $PGE_2$ contents and 5-LPO activities indicating inflammatory responses of the primary cultured rat articular chondrocytes, and also decreases of cell viabilities, increases of MMP-2 and MMP-9 activities with decreases of extracellular matrix (ECM) related collagen type II, SOX9 and aggrecan mRNA expressions were observed by treatment of $rhIL-1{\alpha}$ 50 ng/ml, suggesting damages on the primary cultured rat articular chondrocytes and related ECM degradations. However, these inflammatory responses and related ECM degradations were inhibited by pretreatment of all test substances, in order of PCP > ECe > ARe > EC > AR, and $rhIL-1{\alpha}$ induced chondrocytes deaths are inhibited by treatment in order of PCP > EC > AR > ECe > ARe. Conclusions : Taken together, it is expected that mixed formulation of PCP as main components with appropriate proportion of EC and AR as additional components will be achieved a potent alternative medicinal food for osteoarthritis.

Inhibitory effect of Aralia elata ethanol extract against skin damage in UVB-exposed human keratinocytes and human dermal fibroblasts (두릅순 에탄올 추출물의 인간유래 피부각질형성세포와 피부섬유아세포에서의 자외선에 의한 광노화 억제효과)

  • Yang, Jiwon;Kwak, Chungshil
    • Journal of Nutrition and Health
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    • v.49 no.6
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    • pp.429-436
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    • 2016
  • Purpose: Solar ultraviolet (UV) radiation causes inflammation and matrix metalloproteinase (MMP) overexpression and extracellular matrix depletion, leading to skin photoaging such as wrinkle formation, dryness, and sagging. Activation of MMP is influenced by various molecules such as reactive oxygen species (ROS), proinflammatory cytokines, and transient receptor potential vanilloid type (TRPV)-1, which are increased in UV-irradiated skin cells. Aralia elata (AE) ethanolic extract was reported to inhibit ROS generation caused by UVB-irradiation in keratinocytes. In this study, we investigated the photoprotective effect of AE ethanolic extract on UVB-irradiated human keratinocytes (HaCaT) and human dermal fibroblasts (HDF). Methods: AE was freeze-dried, extracted in 70% ethanol, and concentrated. Skin cells were treated with AE extract for 24 h and then exposed to UVB ($55mJ/cm^2$). After 48 h of incubation, proinflammatory cytokines, MMP-1, type-1 procollagen, and TRPV-1 levels were measured by ELISA or Western blotting. Results: Treatment with AE extract ($100{\mu}g/mL$) significantly inhibited UVB-induced IL-6, IL-8, and $PGE_2$ production in HaCaT by 25.6%, 5.3%, and 70.2%, respectively, and also inhibited elevation of MMP-1 and TRPV-1 caused by UVB irradiation by 20.0% and 41.9%, respectively (p < 0.05). In HDF, AE extract treatment significantly inhibited both elevation of MMP-1 and reduction of type-1 procollagen caused by UVB irradiation (p < 0.05). In addition, type-1 procollagen was elevated by AE extract treatment in normal HDFs (p < 0.05). Conclusion: AE 70% ethanol extract has photoprotective ability via reduction of proinflammatory mediators, TRPV-1 and MMP-1 production, and elevation of collagen synthesis. Our findings suggest that AE extract might be a good natural material to protect against UVB-induced premature skin aging.

Cordycepin Inhibits Migration and Invasion of HCT116 Human Colorectal Carcinoma Cells by Tightening of Tight Junctions and Inhibition of Matrix Metalloproteinase Activity (Cordycepin의 치밀결합 강화 및 MMPs의 활성 억제를 통한 HCT116 인체대장암세포의 이동성 및 침윤성의 억제)

  • Jeong, Jin Woo;Choi, Yung Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.1
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    • pp.86-92
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    • 2014
  • Cordycepin is the major functional component of Cordyceps species and is widely used in traditional oriental medicine. Cordycepin has been shown to possess many pharmacological properties, such as enhancement of immune function along with anti-inflammatory, antioxidant, anti-aging, and anti-cancer effects. Here, we investigated the inhibitory effects of cordycepin on cell migration and invasion, which are two critical cellular processes that are often deregulated during metastasis, using HCT116 human colorectal carcinoma cells. According to our data, cordycepin at non-cytotoxic concentrations markedly inhibited the motility and invasiveness of HCT116 cells in a time-dependent manner. RT-PCR and Western blotting results indicated that cordycepin reduced the levels of claudin proteins, which are major components of tight junctions (TJs), and induced tightening of TJs. Cordycepin also attenuated the expression and activities of matrix metalloproteinases (MMPs)-2 and -9, whereas levels of tissue inhibitor of metalloproteinases (TIMPs)-1 and -2 were simultaneously elevated. These findings suggest that cordycepin reduces the migration and invasion of HCT116 cells by modulating the activities of TJs and MMPs.