2.50
Hdl Handle:
http://hdl.handle.net/10541/78217
Title:
CD105 prevents apoptosis in hypoxic endothelial cells.
Authors:
Li, Chenggang; Issa, Razao; Kumar, Patricia; Hampson, Ian N; Lopez-Novoa, Jose M; Bernabeu, Carmelo; Kumar, Shant
Abstract:
CD105, a marker of endothelial cells, is abundantly expressed in tissues undergoing angiogenesis and is a receptor for transforming growth factorbeta. 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 TGFbeta1. Furthermore, hypoxia and TGFbeta1 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.
Affiliation:
Department of Pathology, Medical School, University of Manchester and Christie Hospital, Manchester M13 9PT, UK.
Citation:
CD105 prevents apoptosis in hypoxic endothelial cells. 2003, 116 (Pt 13):2677-85 J. Cell. Sci.
Journal:
Journal of Cell Science
Issue Date:
1-Jul-2003
URI:
http://hdl.handle.net/10541/78217
DOI:
10.1242/jcs.00470
PubMed ID:
12746487
Type:
Article
Language:
en
ISSN:
0021-9533
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Chenggang-
dc.contributor.authorIssa, Razao-
dc.contributor.authorKumar, Patricia-
dc.contributor.authorHampson, Ian N-
dc.contributor.authorLopez-Novoa, Jose M-
dc.contributor.authorBernabeu, Carmelo-
dc.contributor.authorKumar, Shant-
dc.date.accessioned2009-08-21T14:09:53Z-
dc.date.available2009-08-21T14:09:53Z-
dc.date.issued2003-07-01-
dc.identifier.citationCD105 prevents apoptosis in hypoxic endothelial cells. 2003, 116 (Pt 13):2677-85 J. Cell. Sci.en
dc.identifier.issn0021-9533-
dc.identifier.pmid12746487-
dc.identifier.doi10.1242/jcs.00470-
dc.identifier.urihttp://hdl.handle.net/10541/78217-
dc.description.abstractCD105, a marker of endothelial cells, is abundantly expressed in tissues undergoing angiogenesis and is a receptor for transforming growth factorbeta. 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 TGFbeta1. Furthermore, hypoxia and TGFbeta1 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.en
dc.language.isoenen
dc.subject.meshAntigens, CD-
dc.subject.meshApoptosis-
dc.subject.meshCaspases-
dc.subject.meshCell Hypoxia-
dc.subject.meshCells, Cultured-
dc.subject.meshCyclin D1-
dc.subject.meshEndothelial Cells-
dc.subject.meshG1 Phase-
dc.subject.meshGenes, cdc-
dc.subject.meshHumans-
dc.subject.meshNeovascularization, Pathologic-
dc.subject.meshOligonucleotides, Antisense-
dc.subject.meshPromoter Regions, Genetic-
dc.subject.meshRNA, Messenger-
dc.subject.meshReceptors, Cell Surface-
dc.subject.meshStress, Physiological-
dc.subject.meshTransforming Growth Factor beta-
dc.subject.meshUp-Regulation-
dc.subject.meshVascular Cell Adhesion Molecule-1-
dc.titleCD105 prevents apoptosis in hypoxic endothelial cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, Medical School, University of Manchester and Christie Hospital, Manchester M13 9PT, UK.en
dc.identifier.journalJournal of Cell Scienceen

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