| Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis. | |
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MedLine Citation:
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PMID: 22053071 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated in innate immunity, cell polarity, and differentiation. Here we studied the role of DMBT1 in endothelial cells. METHODS AND RESULTS: DMBT1 was secreted into the extracellular matrix (ECM) by endothelial cells in vitro and in situ and the presence of DMBT1 in the ECM increased endothelial cell adherence. Endothelial cell-derived DMBT1 associated with galectin-3 (coprecipitation), and human recombinant DMBT1 bound EGF, vascular endothelial growth factor and Delta-like (Dll) 4 (specific ELISAs). Compared to cells from wild-type mice, endothelial cells from DMBT1(-/-) mice demonstrated reduced migration, proliferation, and tube formation. In vivo recovery from hindlimb ischemia was attenuated in DMBT1(-/-) animals as was vascular endothelial growth factor -induced endothelial sprouting from isolated aortic rings; the latter response could be rescued by the addition of recombinant DMBT1. The Notch pathway is involved in multiple aspects of vascular development, including arterial-venous differentiation and we found that endothelial cells from DMBT1(-/-) mice expressed more EphrinB2 than cells from wild-type mice. Levels of Dll1, Dll4, Hes1, Hey1, and EphB4, on the other hand, were increased. CONCLUSIONS: Taken together, the results of this study indicate that DMBT1 functions as an important endothelium-derived ECM protein that is able to bind angiogenic factors and promote adhesion, migration, proliferation, and angiogenesis as well as vascular repair. Mechanistically, DMBT1 interacts with galectin-3 and modulates the Notch signaling pathway as well as the differential expression of ephrin-B2 and EphB4. |
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Authors:
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Hanna Müller; Jiong Hu; Rüdiger Popp; Mirko H H Schmidt; Karin Müller-Decker; Jan Mollenhauer; Beate Fisslthaler; Johannes A Eble; Ingrid Fleming |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-3 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: - ISSN: 1524-4636 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institute for Vascular Signalling and Institute for Vascular Matrix Biology, Centre for Molecular Medicine and Institute of Neurology, Goethe University, Frankfurt, Germany; Core Facility Tumor Models, German Cancer Research Centre, Heidelberg, Germany; Lundbeckfonden Center of Excellence NanoCAN and Molecular Oncology, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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