• Title/Summary/Keyword: MMP9

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Protective Effects of Portulaca oleracea L. Extract against Matrix Metalloproteinase Production and Reactive Oxygen Species Generation Induced by Ultraviolet B Radiation in Human Keratinocytes (쇠비름 추출물의 UVB 자외선 조사에 의한 인간각질형성세포 손상에 대한 보호 효과)

  • Oh, Jung Hwan;Karadeniz, Fatih;Lee, Jung Im;Park, So Young;Seo, Youngwan;Kong, Chang-Suk
    • Journal of Life Science
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    • v.28 no.8
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    • pp.892-899
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    • 2018
  • Portulaca oleracea L. is an edible plant widely consumed in daily diet throughout Europe, Asia and America. In this study, protective effects of P. oleracea L. extracts against oxidative stress and matrix metalloproteinase (MMP) activity induced by ultraviolet B (UVB) radiation were investigated using HaCaT immortal human keratinocytes. In this context, the mRNA and protein productions of MMPs (MMP-1, -2, and -9) and type I procollagen, which are major markers of photoaging induced by UVB radiation in HaCaT keratinocytes, were evaluated. Furthermore, UVB-induced reactive oxygen species (ROS) generation and mRNA and protein expression levels of superoxide dismutase-1 (SOD-1), oxygenase-1 (OH-1), and nuclear factor-erythroid 2-related factor-2 (Nrf-2), all of which are associated with the antioxidant balance, were investigated. As shown by the results, UVB radiation induced ROS formation and led to increased production of MMPs and decreased collagen production in human keratinocytes, which resulted in skin photoaging or photodamage. The treatment with P. oleracea L. extracts downregulated MMP (MMP-1, -2, and -9) production and upregulated type I procollagen expression in UVB-induced HaCaT cells. Furthermore, treatment with the extracts decreased UVB-induced ROS generation and increased the expression of antioxidant enzymes, such as SOD-1 and OH-1, through the Nrf-2 pathway. Taken together, these results suggest that P. oleracea L. extracts could be a potential cosmeceutical agent for the prevention of skin photoaging or photodamage.

A Study on the Antioxidant and MMPs Protein Expression Inhibitive Effect of Punica granatum L. Extract and Its Stabilization with Liquid Crystal Emulsion (석류추출물의 항산화와 MMPs 단백질 발현 억제 및 액정 유화물에서의 안정화에 관한 연구)

  • Roh, Jin-Sun;Yeom, Hyeon-Ji;Oh, Min-Jeong;Lee, Jin-Young
    • Journal of Life Science
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    • v.31 no.2
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    • pp.164-174
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    • 2021
  • This study confirmed the potential of Punica granatum L. extract for functional activity verification and cosmetic development. The electron-donating ability of Punica granatum L. extract was shown 60.6% at a 1,000 ㎍/ml concentration. Its ABTS+ radical scavenging ability was shown 93.9% at a 1,000 ㎍/ml concentration. Additionally, the inhibitive effects of elastase and collagenase inhibition effects were measured as 30% and 47.2%, respectively, at a 1,000 ㎍/ml concentration. To determine the effect of Punica granatum L. extract on the proliferation of fibroblasts (CCD-986sk), cell viability was measured using a 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay. As a result, survival rates of 130% or higher at a 500 ㎍/ml concentration or less were confirmed. According to the results of Western blot with Punica granatum L. extract, the expression inhibition rates of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-3 (MMP-3) were decreased by 23.2%, 81.9%, and 69.2%, respectively, at a 100 ㎍/ml concentration. Based on the results above, O/W liquid crystal cream with 0.1% Punica granatum L. extract was prepared. The stabilities were tested at 4, 25, 45, and 50℃. By checking the pH, change over time, and stability by temperature, it was confirmed that all were stable for one month. Thus, Punica granatum L. extract shows potential as a natural material for cosmetics.

Identification of ANXA1 as a Lymphatic Metastasis and Poor Prognostic Factor in Pancreatic Ductal Adenocarcinoma

  • Liu, Qing-Hua;Shi, Mei-Lin;Bai, Jin;Zheng, Jun-Nian
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2719-2724
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    • 2015
  • Objective: The aim of this study was to investigate the clinical significance of annexin a1 (ANXA1) and provide molecular evidence to support that decreased ANXA1 expression could enhance cancer migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Immunohistochemistry of a tissue microarray with 162 surgically resected PDAC specimens was performed to examine the expression of ANXA1. We also investigated the relationship between ANXA1 expression and clinicopathological factors and prognosis of PDAC patients. We further studied the role of ANXA1 in PDAC cell proliferation, migration and invasion by cell proliferation assay, migration assay and matrigel invasion assay with reduced ANXA1 expression by RNAi. Western blotting was used to detect matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. We also detected MMP-9 enzyme activity by gelatin zymography. Results: Decreased expression of ANXA1 was significantly associated with poor differentiation, lymph node metastasis and advanced TNM stage of PDAC patients (p<0.05). Moreover, decreased expression of ANXA1 was correlated with poor survival (p<0.05). Furthermore, we found that ANXA1 knockdown inhibited cell proliferation, induced G1 phase cell cycle arrest, increased PDAC cell migration and invasion capacity compared with controls. In addition, Western blotting showed that ANXA1 knockdown increased the MMP-9 protein level and decreased TIMP-1 expression. Gelatin zymography showed that MMP-9 enzyme activity was also elevated. Conclusions: Negative ANXA1 expression is a most unfavorable prognostic factor for PDAC patients. ANXA1 knockdown inhibits cell proliferation by inducing G1 phase cell cycle arrest and increases migration and invasion of PDAC cells through up-regulating MMP-9 expression and activity, implying that ANXA1 may serve as a promising prognostic biomarker and therapeutic target for PDAC.

Chemokine Lkn-1/CCL15 enhances matrix metalloproteinase-9 release from human macrophages and macrophage-derived foam cells

  • Kwon, Sang-Hee;Ju, Seong-A;Kang, Ji-Hye;Kim, Chu-Sook;Yoo, Hyeon-Mi;Yu, Ri-Na
    • Nutrition Research and Practice
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    • v.2 no.2
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    • pp.134-137
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    • 2008
  • Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCLl5), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions playa crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCLl5 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis.

Water Extracts of Aralia elata Root Bark Enhances Migration and Matrix Metalloproteinases Secretion in Porcine Coronary Artery Endothelial Cells

  • Oh, In-Suk;Han, Ji-Won;Kim, Hwan-Gyu
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.10 no.4
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    • pp.372-377
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    • 2005
  • Aralia elata is an edible mountain vegetable. Angiogenesis, the formation of new blood vessels, is a process involving migration, proliferation and cell differentiation, as well as the formation of new capillary structures. Matrix metalloproteinases (MMPs) plays an important role in angiogenesis. The development of a functional vascular system requires a variety of growth factors, their receptors, and intracellular signals. This study examines the effects of water extracts from: (i) A. elata root bark (Aralia extracts); (ii) a combination of Aralia extracts and fibroblast growth factors (FGF-2) on cultured porcine coronary artery endothelial cells (PCAECs). Aralia extracts induced the migration of PCAECs, which was inhibited by MMPs inhibitors. Combining Aralia extracts and FGF-2 enhanced the migration and the secretion of MMP-2 and MMP­9 from PCAECs. We postulated that the Aralia extracts, which induced migrating activity in PCAECs, may be accomplished by increased secretion levels of MMP-2 and MMP-9.

Inhibitory Effects of Nude Pack Containing Black Tea Water Extract on Skin Wrinkle Formation in Hairless Mice (홍차추출물 함유 누드팩의 Hairless 마우스 피부주름 형성 억제효과)

  • Kim, Young-Chul;Park, Eun-Ye;Kim, Sang-Nam;Yoo, Yong-Gi;Park, Mi-Soon;Lee, Gui-Yeong;Lee, Suk-Jun;Chang, Byung-Soo
    • Applied Microscopy
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    • v.41 no.2
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    • pp.129-137
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    • 2011
  • The aim of this study was to evaluate the inhibitory effect of nude pack containing black tea water extract (NPBT) on skin wrinkle formation in hairless mice. Skin wrinkles were induced by UVB irradiation to the backs of hairless mice for 5 weeks. And at the same time, NPBT was applied topically. Wrinkle formation, histological changes, expression of matrix metalloproteinase-3 (MMP-3) and protein activities of MMP-2 and MMP-9 were observed or analyzed. Wrinkles for the control group were formed as a pattern of deep furrows and thick crests. Whereas wrinkles for the NPBT treated group were formed as a pattern of shallow furrows and thin crests, and their wrinkle areas were significantly (p<0.001) lower than the control group. Collagen fibers were arranged irregularly and sparse in density and some elastic fibers were degenerated in the control group, while they were almost intact in the NPBT treated group. MMP-3 mRNA expression in the control group was significantly (p<0.001) higher than the normal group, and that of NPBT treated group was significantly (p<0.001) lower than the control group. The NPBT treated group showed remarkably lower protein activities of MMP-2 and MMP-9 than the control group. NPBT could have a considerable inhibitory effect on skin wrinkle formation in hairless mice.

Over-expression of MMP-3 in the fissured tissue of cleft lip and palate

  • Park, Young-Wook;Min, Bong-Gi;Kim, Ji-Hyuck;Kim, Soung-Min;Lee, Young-Joon;Lee, Sang-Shin;Lee, Suk-Keun;Moon, Huck-Soo;Chi, Je-Geun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.1
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    • pp.19-26
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    • 2006
  • Objective: In order to elucidate the retrogressive degeneration of orofacial cleft, the fissured tissues of prenatal and postnatal cleft lip and palate were examined by histological and immunohistochemical methods. Design: Totally 42 cases of prenatal (n=17) and postnatal (n=25) cleft lip and/or palate were examined in comparison with 10 cases of normal lip and oral mucosa using immunohistochemical stainings of MMP-3, MMP-9, MMP-10, cathepsin G, PCNA, E-cadherin, TGase 2, HSP-70, vWF, and VEGF. Main Outcome Measures: In the fissured tissue the sebaceous glands were strongly positive for PCNA and grew into the underlying fibromuscular tissue (24/42). Some hyperplastic sebaceous glands of prenatal cleft lip produced infundibular follicular cyst (9/17). The skin and mucosal epithelia from the postnatal cleft lip and palate (10/25) showed severe basal hyperplasia (11/25) and melanocyte infiltration (7/25). Results: The immunostaining of MMP-3 and HSP-70 were strongly positive in the hyperplastic sebaceous glands and nearby atrophying muscle bundles of the fissured tissue, while MMP-9, MMP-10, and cathepsin G were almost negative. The immunoreactions of the other antibodies used in this study were similar between in the fissured tissues and in the normal controls. Conclusions: These data suggest that the over-expression of MMP-3 is closely related to the sebaceous gland hyperplasia, epithelial dysplasia, and the muscle degeneration, and that the over-expression of MMP-3 in the fissured tissue may continuously aggravate the cleft condition in the later life.

Effect of Cnidium japonicum Miq. Crude Extracts on UVB-induced Photoaging Damage in Human Keratinocytes (HaCaT 세포에서 UVB로 유도된 광노화에 대한 갯사상자 추출물의 효능)

  • Eun Seong Lee;Jung Hwan Oh;Chang-Suk Kong;Youngwan Seo
    • Journal of Life Science
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    • v.33 no.5
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    • pp.414-421
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    • 2023
  • Cnidium japonicum (C. japonicum) is a type of halophyte that inhabits soil of a high salinity, and according to previous studies, it is known to have antitumor effects. However, the skin's protective effect, particularly against UVB irradiation, has not been revealed. In this study, C. japonicum crude extract was studied to determine its effect on damage to human keratinocytes (HaCaT) induced by UVB irradiation, and ROS assays were performed, the results of which showed that C. japonicum crude extract affects UVB-induced photoaging damage in human keratinocytes. To examine inhibitory effects against the expressions of MMPs, RT-PCR and Western blot assay were performed by treating the crude extract at concentrations of 10, 50, and 100 ㎍/ml by irradiating UVB at 15 mJ/cm2. As a result, it was confirmed that the mRNA and protein expression levels of MMP-1, MMP-3, and MMP-9 decreased in the group treated with C. japonicum crude extract, which also effectively regulated the antioxidant defense mechanism pathway by activating JNK, ERK, and p38. In conclusion, the current study suggested the possibility that C. japonicum could be used as a raw material for anti-photoaging cosmeceuticals in the future.

Vitamin D maintains E-cadherin intercellular junctions by downregulating MMP-9 production in human gingival keratinocytes treated by TNF-α

  • Oh, Changseok;Kim, Hyun Jung;Kim, Hyun-Man
    • Journal of Periodontal and Implant Science
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    • v.49 no.5
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    • pp.270-286
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    • 2019
  • Purpose: Despite the well-known anti-inflammatory effects of vitamin D in periodontal health, its mechanism has not been fully elucidated. In the present study, the effect of vitamin D on strengthening E-cadherin junctions (ECJs) was explored in human gingival keratinocytes (HGKs). ECJs are the major type of intercellular junction within the junctional epithelium, where loose intercellular junctions develop and microbial invasion primarily occurs. Methods: HOK-16B cells, an immortalized normal human gingival cell line, were used for the study. To mimic the inflammatory environment, cells were treated with tumor necrosis factor-alpha ($TNF-{\alpha}$). Matrix metalloproteinases (MMPs) in the culture medium were assessed by an MMP antibody microarray and gelatin zymography. The expression of various molecules was investigated using western blotting. The extent of ECJ development was evaluated by comparing the average relative extent of the ECJs around the periphery of each cell after immunocytochemical E-cadherin staining. Vitamin D receptor (VDR) expression was examined via immunohistochemical analysis. Results: $TNF-{\alpha}$ downregulated the development of the ECJs of the HGKs. Dissociation of the ECJs by $TNF-{\alpha}$ was accompanied by the upregulation of MMP-9 production and suppressed by a specific MMP-9 inhibitor, Bay 11-7082. Exogenous MMP-9 decreased the development of ECJs. Vitamin D reduced the production of MMP-9 and attenuated the breakdown of ECJs in the HGKs treated with $TNF-{\alpha}$. In addition, vitamin D downregulated $TNF-{\alpha}$-induced nuclear factor kappa B ($NF-{\kappa}B$) signaling in the HGKs. VDR was expressed in the gingival epithelium, including the junctional epithelium. Conclusions: These results suggest that vitamin D may avert $TNF-{\alpha}$-induced downregulation of the development of ECJs in HGKs by decreasing the production of MMP-9, which was upregulated by $TNF-{\alpha}$. Vitamin D may reinforce ECJs by downregulating $NF-{\kappa}B$ signaling, which is upregulated by $TNF-{\alpha}$. Strengthening the epithelial barrier may be a way for vitamin D to protect the periodontium from bacterial invasion.

Effect of Gastrodiae Rhizoma on Apoptosis in Cerebral Infarction Induced by Middle Cerebral Artery Occlusion in Rats (천마가 중대뇌동맥 폐쇄 흰쥐의 신경세포 자연사에 미치는 영향)

  • Youn, You-Suk;Lee, Jong-Soo
    • Journal of Korean Medicine Rehabilitation
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    • v.19 no.3
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    • pp.1-13
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    • 2009
  • Objectives : This study evaluates neuroprotective effect of Gastrodiae Rhizoma on apoptosis in the cerebral infarct. Methods : Cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with intraluminal thread method in Sprague-Dawley rats. Then ethanol extract of Gastrodiae Rhizoma was administered orally for 3 days. Infarct area and volume were evaluated with TTC staining. Neuronal apoptosis was identified with TUNEL labeling. Apoptosis modulatory effect was observed with immunohistochemical Bax, Bcl-2, iNOS, and MMP-9 expressions in penumbra. Results : 1. Ethanol extract of Gastrodiae Rhizoma reduced infarct size partly and volume significantly of in the MCAO rat brain. 2. Ethanol extract of Gastrodiae Rhizoma reduced TUNEL positive cell ratio in the penumbra of MCAO rat brain significantly. 3. Ethanol extract of Gastrodiae Rhizoma suppressed Bax, iNOS and MMP-9 expression in the penumbra of MCAO rat brain significantly. 4. Ethanol extract of Gastrodiae Rhizoma did not change Bcl-2 expression in the penumbra of MCAO rat brain. But expression ratio of Bcl-2 against Bax was increased in the Gastrodiae Rhizoma group. Conclusions : These results suggest that Gastrodiae Rhizoma plays an anti-apoptotic neuroprotective effect through suppression of Bax, iNOS, and MMP-9 expressions and relative up-regulation of Bcl-2 in the ischemic brain tissue.