• Title/Summary/Keyword: Extracellular Matrix Proteins

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An Overview of Matrix Metalloproteinase 9 Polymorphism and Gastric Cancer Risk

  • Verma, Sugreev;Kesh, Kousik;Gupta, Arnab;Swarnakar, Snehasikta
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7393-7400
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    • 2015
  • Matrix metalloproteinase (MMP) 9, a key member of multifunctional family of zinc dependent endopeptidases has been found to be upregulated during inflammation and in some cancers. MMPs cleave extracellular matrix (ECM) proteins and play critical roles in cellular apoptosis, angiogenesis, tumor growth and metastasis. Several genetic polymorphisms have been identified that show allele specific effects on MMP9 regulation and are associated with gastric cancer, the fourth most common malignancy in the world. Besides Helicobacter pylori infection, genetic predisposition is another documented risk factor for gastric carcinoma. The single nucleotide polymorphism (SNP) at position -1562C/T of MMP9 results in the modulation for binding of transcription factors to the MMP9 gene promoter and thereby causes differences in protein expression and enzymatic activity. MMP9 transcriptional regulation during gastric cancer development remains poorly known although several studies have demonstrated associations between MMP9 -1562 C/T polymorphism with different diseases. Knowledge on mechanisms of MMP9 upregulation during gastric cancer may provide new paradigm in diagnostics and therapeutics.

Matrix Metalloproteinases, New Insights into the Understanding of Neurodegenerative Disorders

  • Kim, Yoon-Seong;Joh, Tong-H.
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.133-143
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    • 2012
  • Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are re-sponsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, com-partmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain devel-opment, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer's disease, multiple sclerosis, ischemia/reperfusion and Parkinson's disease. We further highlight accumu-lating evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflamma-tion, apoptosis and degradation of ${\alpha}$-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.

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.

Comparative secretome analysis of human follicular dermal papilla cells and fibroblasts using shotgun proteomics

  • Won, Chong-Hyun;Kwon, Oh-Sang;Kang, Yong-Jung;Yoo, Hyeon-Gyeong;Lee, Dong-Hun;Chung, Jin-Ho;Kim, Kyu-Han;Park, Won-Seok;Park, Nok-Hyun;Cho, Kun;Kwon, Sang-Oh;Choi, Jong-Soon;Eun, Hee-Chul
    • BMB Reports
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    • v.45 no.4
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    • pp.253-258
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    • 2012
  • The dermal papilla cells (DPCs) of hair follicles are known to secrete paracrine factors for follicular cells. Shotgun proteomic analysis was performed to compare the expression profiles of the secretomes of human DPCs and dermal fibroblasts (DFs). In this study, the proteins secreted by DPCs and matched DFs were analyzed by 1DE/LTQ FTICR MS/MS, semi-quantitatively determined using emPAI mole percent values and then characterized using protein interaction network analysis. Among the 1,271 and 1,188 proteins identified in DFs and DPCs, respectively, 1,529 were further analyzed using the Ingenuity Pathway Analysis tool. We identified 28 DPC-specific extracellular matrix proteins including transporters (ECM1, A2M), enzymes (LOX, PON2), and peptidases (C3, C1R). The biochemically-validated DPC-specific proteins included thrombospondin 1 (THBS1), an insulin-like growth factor binding protein3 (IGFBP3), and, of particular interest, an integrin beta1 subunit (ITGB1) as a key network core protein. Using the shotgun proteomic technique and network analysis, we selected ITGB1, IGFBP3, and THBS1 as being possible hair-growth modulating protein biomarkers.

Electricity Generation from MFCs Using Differently Grown Anode-Attached Bacteria

  • Nam, Joo-Youn;Kim, Hyun-Woo;Lim, Kyeong-Ho;Shin, Hang-Sik
    • Environmental Engineering Research
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    • v.15 no.2
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    • pp.71-78
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    • 2010
  • To understand the effects of acclimation schemes on the formation of anode biofilms, different electrical performances are characterized in this study, with the roles of suspended and attached bacteria in single-chamber microbial fuel cells (MFCs). The results show that the generation of current in single-chamber MFCs is significantly affected by the development of a biofilm matrix on the anode surface containing abundant immobilized microorganisms. The long-term operation with suspended microorganisms was demonstrated to form a dense biofilm matrix that was able to reduce the activation loss in MFCs. Also, a Pt-coated anode was not favorable for the initial or long-term bacterial attachment due to its high hydrophobicity (contact angle = $124^{\circ}$), which promotes easy detachment of the biofilm from the anode surface. Maximum power ($655.0\;mW/m^2$) was obtained at a current density of $3,358.8\;mA/m^2$ in the MFCs with longer acclimation periods. It was found that a dense biofilm was able to enhance the charge transfer rates due to the complex development of a biofilm matrix anchoring the electrochemically active microorganisms together on the anode surface. Among the major components of the extracellular polymeric substance, carbohydrates ($85.7\;mg/m^2_{anode}$) and proteins ($81.0\;mg/m^2_{anode}$) in the dense anode biofilm accounted for 17 and 19%, respectively, which are greater than those in the sparse anode biofilm.

Cellular and Molecular Pathology of Fungi on Plants Studied by Modern Electron Microscopy

  • Sanwald, Sigrun-Hippe
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 1995.06b
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    • pp.27-53
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    • 1995
  • In plant pathology there is an increasing necessity for improved cytological techniques as basis for the localization of cellular substances within the dynamic fine structure of the host-(plant)-pathogen-interaction. Low temperature (LT) preparation techniques (shock freezing, freeze substitution, LT embedding) are now successfully applied in plant pathology. They are regarded as important tools to stabilize the dynamic plant-pathogen-interaction as it exists under physiological conditions. - The main advantage of LT techniques versus conventional chemical fixation is seen in the maintenance of the hydration shell of molecules and macromolecular structures. This results in an improved fine structural preservation and in a superior retention of the antigenicity of proteins. - A well defined ultrastructure of small, fungal organisms and large biological samples such as plant material and as well as the plant-pathogen (fungus) infection sites are presented. The mesophyll tissue of Arabidopsis thaliana is characterized by homogeneously structured cytoplasm closely attached to the cell wall. From analyses of the compatible interaction between Erysiphe graminis f. sp. hordei on barley (Hordeum vulgare), various steps in the infection sequence can be identified. Infection sites of powdery mildew on primary leaves of barley are analysed with regard to the fine structural preservation of the haustoria. The presentation s focussed on the ultrastructure of the extrahaustorial matrix and the extrahaustorial membrane. - The integration of improved cellular preservation with a molecular analysis of the infected host cell is achieved by the application of secondary probing techniques, i.e. immunocytochemistry. Recent data on the characterization of freeze substituted powdery mildew and urst infected plant tissue by immunogold methodology are described with special emphasis on the localization of THRGP-like (threonine-hydrxyproline-rich glycoprotein) epitopes. Infection sites of powdery mildew on barley, stem rust as well as leaf rust (Puccinia recondita) on primary leaves of wheat were probed with a polyclonal antiserum to maize THRGP. Cross-reactivity with the anti-THRGP antiserum was observed over the extrahaustorial matrix of the both compatible and incompatible plant-pathogen interactions. The highly localized accumulation of THRGP-like epitopes at the extrahaustorial host-pathogen interface suggests the involvement of structural, interfacial proteins during the infection of monocotyledonous plants by obligate, biotrophic fungi.

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Astragalus membranaceus promotes differentiation and mineralization in human osteoblast-like SaOS-2 cells

  • Huh, Jeong-Eun;Kim, Nam-Jae;Yang, Ha-Ru;Cho, Eun-Mi;Baek, Yong-Hyeon;Choi, Do-Young;Kim, Deog-Yoon;Cho, Yoon-Je;Kim, Kang-Il;Park, Dong-Suk;Lee, Jae-Dong
    • Journal of Acupuncture Research
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    • v.22 no.2
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    • pp.181-190
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    • 2005
  • Background & Object : The differentiation of osteoblasts controlled by various growth factors and matrix proteins expression in bone. The aim of this study was to identify the Astragalus membranaceus that may induce the osteogenic activity in human osteoblast-like SaOS-2 cells. Methods : The osteogenic activity of Astragalus membranaceus were evaluated by WST-8 assay, ALP activity, RT-PCR analysis of VEGF, OCN, OPN, Col I mRNA, and ELISA or colorimetric analysis, and mineralization by Alizarin red staining in SaOS-2 cells. Results : Astragalus membranaceus had no effect on viability of osteoblastic cells, and dose dependently increased alkaline phosphatase (ALP) activity. Astragalus membranaceus markedly increased mRNA expression for vascular endothelial growth factor (VEGF), osteocalcin (OCN), osteopontin (OPN), and type I collagen (Col 1) in SaOS-2 cells. Extracellular accumulation of proteins such as VEGF, and Col I was increased in a dose-dependent manner. Also, Astragalus membranaceus significantly induced mineralization in the culture of SaOS-2 cells. Conclusion : This study showed that Astragalus membranaceus not affect on viability, but it enhanced ALP activity, VEGF, bone matrix proteins such as OCN, OPN and Col I, and mineralization in SaOS-2 cells. These results propose that Astragalus membranaceus plays an important role in osteoblastic bone formation, and possibly lead to the development of bone-forming drug.

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Transforming Growth $Factor-{\beta}$ Enhances Tyrosine Phosphorylation of Two Cellular Proteins in HEL Cells

  • Lim, Chang-Su;Chun, Jeong-Seon;Sung, Soo-Kyung;Lee, Kyu-Cheol;Lee, Chan-Hee
    • BMB Reports
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    • v.30 no.2
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    • pp.119-124
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    • 1997
  • Transforming growth $factor-{\beta}\;(TGF-{\beta})$ is a multifunctional polypeptide that exerts biological roles including cell proliferation, differentiation, extracellular matrix deposition and apoptosis in many different cell types. $TGF-{\beta}$, although known as a negative growth regulator, has not been tested in human embryo lung (HEll cells. This study attempts to understand the role of $TGF-{\beta}$ on growth control of HEL cells in relationship to tyrosine phosphorylation pattern of cellular proteins. In density-arrested HEL cells treated with $TGF-{\beta}$, analysis of Western immunoblot showed induction of tyrosine phosphorylation of two major cellular proteins (15 kDa and 45 kDa). In normal proliferating HEL cells with different concentrations of serum, further analysis indicated that the increase in tyrosine phosphorylation of a 45 kDa protein was regulated in serum concentration-dependent manner. However, in proliferating HEL cells treated with $TGF-{\beta}$, tyrosine phosphorylation of 45 kDa was down-regulated. Calcium involvement in the regulation of tyrosine phosphorylation of 45 kDa and 15 kDa proteins was also examined. Tyrosine phosphorylation of 15 kDa protein but not of 45 kDa protein was regulated by exogenous calcium. The level of tyrosine phosphorylation of 15 kDa protein was low at reduced caclium concentration and high at elevated caclium concentration. $TGF-{\beta}$ reversed the pattern of tyrosine phosphorylation of 15 kDa protein. These results suggest that tyrosine phosphorylation of 45 and 15 kDa proteins in HEL cells may be controlled depending on the physiological status of the cells, i.e., low in arrested cells and high in proliferating cells. And the tyrosine phosphorylation of the two proteins appears to be down- or up-regulated by $TGF-{\beta}$.

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Biofilm Signaling, Composition and Regulation in Burkholderia pseudomallei

  • Pravin Kumran Nyanasegran;Sheila Nathan;Mohd Firdaus-Raih;Nor Azlan Nor Muhammad;Chyan Leong Ng
    • Journal of Microbiology and Biotechnology
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    • v.33 no.1
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    • pp.15-27
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    • 2023
  • The incidence of melioidosis cases caused by the gram-negative pathogen Burkholderia pseudomallei (BP) is seeing an increasing trend that has spread beyond its previously known endemic regions. Biofilms produced by BP have been associated with antimicrobial therapy limitation and relapse melioidosis, thus making it urgently necessary to understand the mechanisms of biofilm formation and their role in BP biology. Microbial cells aggregate and enclose within a self-produced matrix of extracellular polymeric substances (EPSs) to form biofilm. The transition mechanism of bacterial cells from planktonic state to initiate biofilm formation, which involves the formation of surface attachment microcolonies and the maturation of the biofilm matrix, is a dynamic and complex process. Despite the emerging findings on the biofilm formation process, systemic knowledge on the molecular mechanisms of biofilm formation in BP remains fractured. This review provides insights into the signaling systems, matrix composition, and the biosynthesis regulation of EPSs (exopolysaccharide, eDNA and proteins) that facilitate the formation of biofilms in order to present an overview of our current knowledge and the questions that remain regarding BP biofilms.

Treatment Response Evaluation of Cardiac Amyloidosis Using Serial T1- and T2-Mapping Cardiovascular Magnetic Resonance Imaging (T1 지도화 기법 심장 자기공명영상 추적 검사를 이용한 심장 아밀로이드증의 치료 반응 평가)

  • Jinwoo Son;Yoo Jin Hong
    • Journal of the Korean Society of Radiology
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    • v.82 no.2
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    • pp.429-434
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    • 2021
  • Amyloidosis is a multisystemic disease characterized by the accumulation of abnormal proteins in extracellular spaces in various organs, with frequent involvement of the myocardium. We report a case of a patient who had cardiac amyloidosis with a trend of reduction in native T1 and T2 values and extracellular volume fraction on serial cardiac magnetic resonance imaging after chemotherapy and stem cell transplantation. The native T1 value and the extracellular volume fraction are closely associated with tissue amyloid burden in amyloidosis patients. This case demonstrated that cardiac magnetic resonance imaging may be used as a non-invasive and quantitative biomarker in the treatment monitoring of amyloidosis.