Abstract:
:Fibulin-5 (FBLN-5) is a widely expressed, integrin-binding extracellular matrix protein that mediates endothelial cell adhesion and scaffolds cells to elastic fibers. It is also a gene target of TGF-beta in fibroblasts and endothelial cells that regulates cell proliferation and motility in a context-specific manner. Whereas FBLN-5 expression is low in adult vasculature, its expression is high in developing and injured vasculature, implicating FBLN-5 in regulating angiogenesis and endothelial cell function. We show here that TGF-beta stimulates FBLN-5 expression in endothelial cells, and that this response was inhibited by coadministration of the proangiogenic factor, VEGF. FBLN-5 expression was downregulated significantly during endothelial cell tubulogenesis, implying that FBLN-5 expression antagonizes angiogenesis. Accordingly, FBLN-5 overexpression in or recombinant FBLN-5 treatment of endothelial cells abrogated their ability to undergo angiogenic sprouting, doing so by inhibiting endothelial cell proliferation and invasion through Matrigel matrices. Moreover, FBLN-5 antagonized VEGF signaling in endothelial cells, as well as enhanced their expression of the antiangiogenic factor, thrombospondin-1. Finally, the ability of FBLN-5 to antagonize angiogenic processes was determined to be independent of its integrin-binding RGD motif. Collectively, our findings establish FBLN-5 as a novel antagonist of angiogenesis and endothelial cell activities, and offer new insights into why tumorigenesis downregulates FBLN-5 expression.
journal_name
DNA Cell Bioljournal_title
DNA and cell biologyauthors
Albig AR,Schiemann WPdoi
10.1089/104454904323145254keywords:
subject
Has Abstractpub_date
2004-06-01 00:00:00pages
367-79issue
6eissn
1044-5498issn
1557-7430journal_volume
23pub_type
杂志文章abstract::In this investigation, we examined the role of the Axl proto-oncogene in renal cell carcinoma (RCC). Axl is a tyrosine kinase receptor implicated in myeloid leukogenesis, and has been found to be overexpressed in lung cancers and breast cancers. Axl has been described to act as a mitogenic factor along with its ligand...
journal_title:DNA and cell biology
pub_type: 杂志文章
doi:10.1089/10445490360708946
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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doi:10.1089/dna.1997.16.9
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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更新日期:1997-05-01 00:00:00
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journal_title:DNA and cell biology
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doi:10.1089/dna.1996.15.339
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journal_title:DNA and cell biology
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doi:10.1089/104454904322759911
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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journal_title:DNA and cell biology
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doi:10.1089/dna.2008.0801
更新日期:2009-02-01 00:00:00
abstract::The activation of H-plk (Human-proviral linked Krüppel), a human Krüppel-related zinc finger gene in organs such as placenta, adrenal cortex, and testis, is probably due to insertion of an endogenous retrovirus, ERV3, upstream of the gene. Several differently spliced transcripts originate from this locus, e.g., a tran...
journal_title:DNA and cell biology
pub_type: 杂志文章
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更新日期:1998-01-01 00:00:00