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  1. Article ; Online: Proteomic profiling of secreted proteins for the hematopoietic support of interleukin-stimulated human umbilical vein endothelial cells.

    Bal, Gürkan / Kamhieh-Milz, Julian / Sterzer, Viktor / Al-Samman, Muhammad / Debski, Janusz / Klein, Oliver / Kamhieh-Milz, Sundrela / Bhakdi, Sucharit / Salama, Abdulgabar

    Cell transplantation

    2013  Volume 22, Issue 7, Page(s) 1185–1199

    Abstract: Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly impact the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). These factors remain largely unknown. Here, we report on the ... ...

    Abstract Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly impact the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). These factors remain largely unknown. Here, we report on the most comprehensive proteomic profiling of the HUVEC secretome and identified 827 different secreted proteins. Two hundred and thirty-one proteins were found in all conditions, whereas 369 proteins were identified only under proinflammatory conditions following IL-1β, IL-3, and IL-6 stimulation. Thirteen proteins including complement factor b (CFb) were identified only under IL-1β and IL-3 conditions and may potentially represent HSPC proliferation factors. The combination of bioinformatics and gene ontology annotations indicates the role of the complement system and its activation. Furthermore, CFb was found to be transcriptionally strongly upregulated. Addition of complement component 5b-9 (C5b-9) monoclonal antibody to the stem cell expansion assay was capable of significantly reducing their proliferation. This study suggests a complement-mediated cross-talk between endothelial cells and HSPCs under proinflammatory conditions.
    MeSH term(s) Antibodies, Monoclonal/pharmacology ; Antigens, CD34/metabolism ; Cell Proliferation/drug effects ; Complement C5b/immunology ; Complement System Proteins/metabolism ; Computational Biology ; Electrophoresis, Polyacrylamide Gel ; Flow Cytometry ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/drug effects ; Hematopoietic Stem Cells/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Interleukin-1beta/pharmacology ; Interleukin-3/pharmacology ; Interleukin-6/pharmacology ; Peptides/analysis ; Proteomics ; Spectrometry, Mass, Electrospray Ionization ; Up-Regulation
    Chemical Substances Antibodies, Monoclonal ; Antigens, CD34 ; Interleukin-1beta ; Interleukin-3 ; Interleukin-6 ; Peptides ; Complement C5b (80295-55-2) ; Complement System Proteins (9007-36-7)
    Language English
    Publishing date 2013
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1135816-6
    ISSN 1555-3892 ; 0963-6897
    ISSN (online) 1555-3892
    ISSN 0963-6897
    DOI 10.3727/096368912X657288
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3556: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Chemokine Cxcl9 attenuates liver fibrosis-associated angiogenesis in mice.

    Sahin, Hacer / Borkham-Kamphorst, Erawan / Kuppe, Christoph / Zaldivar, Mirko Moreno / Grouls, Christoph / Al-samman, Muhammad / Nellen, Andreas / Schmitz, Petra / Heinrichs, Daniel / Berres, Marie-Luise / Doleschel, Dennis / Scholten, David / Weiskirchen, Ralf / Moeller, Marcus J / Kiessling, Fabian / Trautwein, Christian / Wasmuth, Hermann E

    Hepatology (Baltimore, Md.)

    2012  Volume 55, Issue 5, Page(s) 1610–1619

    Abstract: Unlabelled: Recent data suggest that the chemokine receptor CXCR3 is functionally involved in fibroproliferative disorders, including liver fibrosis. Neoangiogenesis is an important pathophysiological feature of liver scarring, but a functional role of ... ...

    Abstract Unlabelled: Recent data suggest that the chemokine receptor CXCR3 is functionally involved in fibroproliferative disorders, including liver fibrosis. Neoangiogenesis is an important pathophysiological feature of liver scarring, but a functional role of angiostatic CXCR3 chemokines in this process is unclear. We therefore investigated neoangiogenesis in carbon tetrachloride (CCl(4))-induced liver fibrosis in Cxcr3(-/-) and wildtype mice by histological, molecular, and functional imaging methods. Furthermore, we assessed the direct role of vascular endothelial growth factor (VEGF) overexpression on liver angiogenesis and the fibroproliferative response using a Tet-inducible bitransgenic mouse model. The feasibility of attenuation of angiogenesis and associated liver fibrosis by therapeutic treatment with the angiostatic chemokine Cxcl9 was systematically analyzed in vitro and in vivo. The results demonstrate that fibrosis progression in Cxcr3(-/-) mice was strongly linked to enhanced neoangiogenesis and VEGF/VEGFR2 expression compared with wildtype littermates. Systemic VEGF overexpression led to a fibrogenic response within the liver and was associated with a significantly increased Cxcl9 expression. In vitro, Cxcl9 displayed strong antiproliferative and antimigratory effects on VEGF-stimulated endothelial cells and stellate cells by way of reduced VEGFR2 (KDR), phospholipase Cγ (PLCγ), and extracellular signal-regulated kinase (ERK) phosphorylation, identifying this chemokine as a direct counter-regulatory molecule of VEGF signaling within the liver. Accordingly, systemic administration of Cxcl9 led to a strong attenuation of neoangiogenesis and experimental liver fibrosis in vivo.
    Conclusion: The results identify direct angiostatic and antifibrotic effects of the Cxcr3 ligand Cxcl9 in a model of experimental liver fibrosis. The amelioration of liver damage by systemic application of Cxcl9 might offer a novel therapeutic approach for chronic liver diseases associated with increased neoangiogenesis.
    MeSH term(s) Analysis of Variance ; Animals ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL9/metabolism ; Chemokine CXCL9/pharmacology ; Disease Models, Animal ; Flow Cytometry ; Hepatocytes/cytology ; Hepatocytes/metabolism ; Interferon-gamma/metabolism ; Liver Cirrhosis/drug therapy ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; MAP Kinase Signaling System ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/pathology ; Random Allocation ; Vascular Endothelial Growth Factor Receptor-2/metabolism
    Chemical Substances Chemokine CXCL9 ; Interferon-gamma (82115-62-6) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
    Language English
    Publishing date 2012-05
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.25545
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1660: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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