English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/73370
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

CD105 prevents apoptosis in hypoxic endothelial cells

AuthorsLi, Chenggang; Issa, R.; Kumar, Pat; Hampson, I.N.; López-Novoa, José M.; Bernabéu, Carmelo ; Kumar, Shant
Issue Date2003
PublisherCompany of Biologists
CitationJournal of Cell Science 116 (13) 2677- 2685 (2003)
AbstractCD105, a marker of endothelial cells, is abundantly expressed in tissues undergoing angiogenesis and is a receptor for transforming growth factor β. The pivotal role of CD105 in the vascular system was demonstrated by the severe vascular defects that occur in CD105-knockout mice, but the exact mechanisms for CD105 regulation of vascular development have not been fully elucidated. In light of the function of CD105 and the importance of hypoxia in neovascularisation, we speculated that CD105 is involved in hypoxia-initiated angiogenesis. Using tissue-cultured human microvascular endothelial cells, we have investigated the effects of hypoxic stress on CD105 gene expression. Hypoxia induced a significant increase in membrane-bound and secreted CD105 protein levels. CD105 mRNA and promoter activity were also markedly elevated, the latter returning to the basal level after 16 hours of hypoxic stress. Hypoxia induced cell cycle arrest at the G0/G1 phases and massive cell apoptosis after 24 hours through a reduction in the Bcl-2 to Bax ratio, downregulation of Bcl-XL and Mcl-1, and upregulation of caspase-3 and caspase-8. The consequence of CD105 upregulation was revealed using an antisense approach and a TUNEL assay. Suppression of CD105 increased cell apoptosis under hypoxic stress in the absence of TGFβ1. Furthermore, hypoxia and TGFβ1 synergistically induced apoptosis in the CD105-deficient cells but not in the control cells. We conclude that hypoxia is a potent stimulus for CD105 gene expression in vascular endothelial cells, which in turn attenuates cell apoptosis and thus contributes to angiogenesis.
Publisher version (URL)http://doi.org/10.1242/jcs.00470
URIhttp://hdl.handle.net/10261/73370
DOIhttp://dx.doi.org/10.1242/jcs.00470
ISSN0021-9533
E-ISSN1477-9137
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
jcs_Li_2003.pdf274,93 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.