• Title/Summary/Keyword: Extracellular matrix (ECM)

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A Novel Heptapeptide that Promotes Cellular Activity and Inhibits Photoaging in Fibroblasts (섬유아세포에서 세포 활성 촉진 및 광노화 억제 효능을 보이는 신규 헵타펩타이드)

  • Lee, Eung Ji;Kang, Hana;Hwang, Bo Byeol;Chung, Yong Ji;Kim, Eun Mi
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.48 no.2
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    • pp.157-167
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    • 2022
  • In this study, we investigated the effects of heptapeptide on cellular activation and inhibition of cellular damage induced by photoaging condition in NIH3T3 fibroblasts. Cell proliferation and extracellular matrix (ECM) expression were induced by heptapeptide. The reduced cell viability under photoaging condition through ultraviolet A (UVA) irradiation was increased by heptapeptide. And UVA-induced apoptosis, matrix metalloproteinases-1 (MMP-1) expression, and reactive oxygen species (ROS) level were decreased by heptapeptide. In addition, the inhibition of transforming growth factor-β (TGF-β)/smad signaling under UVA irradiation which resulting in reduction of ECM expression was also recovered by heptapeptide. We also tested the effect of heptapeptide under another photoaging condition through heat shock, and pre-treatment of heptapeptide prevented the phosphorylation of mitogen-activated protein kinase (MAPK) and MMP-1 expression induced by heat shock. From these results, it has been shown that the heptapeptide has protective effects on fibroblasts through the up-regulation of cellular activity and through the decreasing of intracellular ROS level induced by UVA irradiation or heat shock. It is expected that the dermal protection effect of heptapeptide can be applied as a new cosmetic material in the future.

Effect of N-Acetylcysteine on the Matrix Metalloproteinases and Their Inhibitors in Carbon Tetrachloride-Induced Hepatotoxicity

  • N, Kamalakkannan;Al-Numair, Khalid S.;Al-Assaf, Abdullah H.;Al-Shatwi, Ali A.;Vp, Menon
    • Preventive Nutrition and Food Science
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    • v.14 no.1
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    • pp.14-20
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    • 2009
  • Matrix metalloproteinases (MMPs) are a group of zinc proteases that serve the function of breaking down extracellular matrix (ECM). The present study evaluated the role of N-acetylcysteine (NAC) on the increased deposition of ECM in hepatic and glomerular fibrosis caused by carbon tetrachloride ($CCl_4$). The activity of MMPs increased and the levels of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) decreased in the liver and kidney of $CCl_4$-treated rats. Rats treated with $CCl_4$ and NAC showed increased activities of MMPs and decreased levels of TIMP-1 and TIMP-2 in the liver and kidney. Treatment with NAC resulted in the effective degradation of ECM due to an increase in the activities of MMPs and a decrease in the levels of TIMPs.

Caveolin-1 inhibits membrane-type 1 matrix metalloproteinase activity

  • Kim, Hye-Nan;Chung, Hye-Shin
    • BMB Reports
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    • v.41 no.12
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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.

Pleiotropic Roles of Metalloproteinases in Hematological Malignancies: an Update

  • Chaudhary, Ajay K;Chaudhary, Shruti;Ghosh, Kanjaksha;Nadkarni, A
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3043-3051
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    • 2016
  • Controlled remodeling of the extracellular matrix (ECM) is essential for cell growth, invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of secreted, zinc-dependent endopeptidases capable of degradation of ECM components. The expression and activity of MMPs in a variety of human cancers have been intensively studied. They play important roles at different steps of malignant tumor formation and have central significance in embryogenesis, tissue remodeling, inflammation, angiogenesis and metastasis. However, increasing evidence demonstrates that MMPs are involved earlier in tumorigenesis. Recent studies also suggest that MMPs play complex roles in tumor progression. MMPs and membrane type (MT)-MMPs are potentially significant therapeutic targets in many cancers, so that designing of specific MMP inhibitors would be helpful for clinical trials. Here, we review the pleiotropic roles of the MMP system in hematological malignancies in-vitro and in-vivo models.

Biomimetic Electrospun Fibers for Tissue Engineering Applications

  • Sin, Heung-Su
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2011.10a
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    • pp.2.2-2.2
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    • 2011
  • The central strategy in tissue engineering involves a biomaterial scaffold as a delivery carrier of cells and a depot to deliver bioactive molecules. The ability of scaffolds to control cellular response to direct particular repair and regeneration processes is essential to obtain functional tissue engineering constructs. Therefore, many efforts have been made to understand local interactions of cells with their extracellular matrix (ECM) microenvironment and exploit these interactions for designing an ideal scaffold mimicking the chemical, physiological, and structural features of native ECM. ECM is composed of a number of biomacromolecules including proteins, glycosaminoglycans, and proteoglycans, which are assembled together to form complex 3-dimensional network. Electrospinning is a process to generate highly porous 3-dimensional fibrous structure with nano to micro scaled-diameter, which can closely mimic the structure of ECM. In this presentation, our approaches to develop biomimetic electrospun fibers for modulation of cell function will be discussed.

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Knockdown of lncRNA PVT1 Inhibits Vascular Smooth Muscle Cell Apoptosis and Extracellular Matrix Disruption in a Murine Abdominal Aortic Aneurysm Model

  • Zhang, Zhidong;Zou, Gangqiang;Chen, Xiaosan;Lu, Wei;Liu, Jianyang;Zhai, Shuiting;Qiao, Gang
    • Molecules and Cells
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    • v.42 no.3
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    • pp.218-227
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    • 2019
  • This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient ($ApoE^{-/-}$) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.

Histologic Analysis of Vocal Folds in Aging Rats (노화 쥐 성대의 조직학적 분석)

  • Shin, Sung-Chan;Kim, Ji Min;Kwon, Hyun-Keun;Cheon, Yong-Il;Lee, Byung-Joo
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.31 no.2
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    • pp.66-70
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    • 2020
  • Background and Objectives Presbyphonia is characterized by hoarse, breathy, weak vocal intensity. Extracellular matrix (ECM) in lamina propria (LP) of the vocal folds play an important role in voice production, and change of ECM according to the aging leads to the presbyphonia. The aim of this study was to investigate the histologic analysis of aging vocal fold of rat. Materials and Method Six and twenty two months old Sprague-Dawley rats (n=8, each group) were used and classified into young (six months old rats) and old (twenty two months old rats) group. Histologic analysis and immunohistochemical staining for ECM of LP were performed. Results Overall cellular density was significantly decreased in old rat group. Elastin fibers of LP were significantly decreased in old rat group. Type I collagen was significantly increased in old rat group. Type III collagen did not show significant difference. Hyaluronic acids did not show significant difference in Alcian blue staining and immunohistochemical staining. Conclusion Decreased general cellular density and elastin fiber and increased type I collagen were observed in the LP of vocal folds of aging rats. These ECM changes might to contribute the aging voice.

Cloning, Purification, and Characterization of Recombinant Human Extracellular Superoxide Dismutase in SF9 Insect Cells

  • Shrestha, Pravesh;Yun, Ji-Hye;Kim, Woo Taek;Kim, Tae-Yoon;Lee, Weontae
    • Molecules and Cells
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    • v.39 no.3
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    • pp.242-249
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    • 2016
  • A balance between production and degradation of reactive oxygen species (ROS) is critical for maintaining cellular homeostasis. Increased levels of ROS during oxidative stress are associated with disease conditions. Antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD), in the extracellular matrix (ECM) neutralize the toxicity of superoxide. Recent studies have emphasized the importance of EC-SOD in protecting the brain, lungs, and other tissues from oxidative stress. Therefore, EC-SOD would be an excellent therapeutic drug for treatment of diseases caused by oxidative stress. We cloned both the full length (residues 1-240) and truncated (residues 19-240) forms of human EC-SOD (hEC-SOD) into the donor plasmid pFastBacHTb. After transposition, the bacmid was transfected into the Sf9-baculovirus expression system and the expressed hEC-SOD purified using FLAG-tag. Western blot analysis revealed that hEC-SOD is present both as a monomer (33 kDa) and a dimer (66 kDa), as detected by the FLAG antibody. A water-soluble tetrazolium (WST-1) assay showed that both full length and truncated hEC-SOD proteins were enzymatically active. We showed that a potent superoxide dismutase inhibitor, diethyldithiocarbamate (DDC), inhibits hEC-SOD activity.

Characterization of Sea Urchin Gonad-derived Extracellular Vesicles and Study of Their Effects on Nerve Cells (성게 생식소 유래 세포외소포체 특성 분석 및 신경세포에 미치는 영향 연구)

  • Byeong-Hoon Choi;Sung-Han Jo;Sang-Hyug Park
    • Journal of Biomedical Engineering Research
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    • v.45 no.1
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    • pp.20-25
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    • 2024
  • Extracellular vesicles (EVs) are nano-sized lipid bilayer vesicles released by cells. EVs act as messengers for cell-to-cell communication. Inside, it contains various substances that show biological activity, such as proteins, lipids, nucleic acids, and metabolites. The study of EVs extracted from terrestrial organisms and stem cells on inflammatory environments and tissue regeneration have been actively conducted. However, marine organisms-derived EVs are limited. Therefore, we have extracted EVs from sea urchins belonging to the Echinoderm group with their excellent regenerative ability. First, we extracted extracellular matrix (ECM) from sea urchin gonads treated with hypotonic buffer, followed by collagenase treatment, and filtration to collect ECM-bounded EVs. The size of sea urchin gonad-derived EVs (UGEVs) is about 20-100 nm and has a round shape. The protein content was higher after EVs burst than before, which is evidence that proteins are contained inside. In addition, proteins of various sizes are distributed inside. PKH-26 was combined with UGEVs, which means that UGEVs have a lipid membrane. PHK-26-labeled UGEVs were successfully uptaken by cells. UGEVs can be confirmed to have the same characteristics as traditional EVs. Finally, it was confirmed that Schwann cells were not toxic by increasing proliferation after treatment.

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

  • Yadav, Lalita;Puri, Naveen;Rastogi, Varun;Satpute, Pranali;Ahmad, Riyaz;Kaur, Geetpriya
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1085-1091
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    • 2014
  • Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.