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rdf:type |
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lifeskim:mentions |
umls-concept:C0028959,
umls-concept:C0205263,
umls-concept:C0302600,
umls-concept:C0631233,
umls-concept:C0813622,
umls-concept:C1314939,
umls-concept:C1332712,
umls-concept:C1332721,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1710082
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pubmed:issue |
4
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pubmed:dateCreated |
2009-9-2
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pubmed:abstractText |
We used short-interfering RNA (siRNA) to knockdown the hyaluronan (HA) receptors CD44 and the receptor for hyaluronan-mediated motility (RHAMM) in vascular endothelial cells to investigate their role in angiogenesis. We showed that CD44 and RHAMM single knockdown inhibited low molecular weight hyaluronan (o-HA)-induced endothelial cell tube formation in Matrigel, but no change in the control, epidermal growth factor-induced tube formation was observed. Using a Kinexus phosphoprotein array and confirmational Western blotting we were able to show a differential effect on HA-induced protein expression after CD44 and RHAMM knockdown. CD44 knockdown abolished o-HA-induced membrane phospho-protein kinase C-alpha (PKC-alpha) and down-stream phospho-gamma-adducin expression. Using the PKC inhibitor Go6976, we demonstrated the involvement of PKC-alpha and gamma-adducin in o-HA-induced tube formation, whilst o-HA-induced enzymatic activity of MMP9 was also reduced. This suggests that endothelial tube formation involves activation of MMP9 via PKC-alpha. Furthermore, the involvement of gamma-adducin in o-HA-induced F-actin cytoskeleton rearrangement was CD44-dependent and the reduction of CD44 expression lead to a change in endothelial cell morphology. Both RHAMM and CD44 knockdown completely inhibited o-HA-induced Cdc2 (Cdk1) phosphorylation suggesting a possible involvement in cell cycle control. Although CD44 and RHAMM are both involved in o-HA-induced endothelial tube formation in Matrigel, they mediate distinct angiogenic signalling pathway and for the first time we demonstrated the specific involvement of gamma-adducin in CD44/o-HA-induced endothelial tube formation. The data presented here extend our understanding of key stages of the processes of o-HA-induced angiogenesis which may have relevance to tumour progression.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD44,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2 Protein Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carbazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Go 6976,
http://linkedlifedata.com/resource/pubmed/chemical/Hyaluronic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Oligosaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/adducin,
http://linkedlifedata.com/resource/pubmed/chemical/hyaluronan-mediated motility...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1791-2423
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
761-73
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pubmed:meshHeading |
pubmed-meshheading:19724912-Actins,
pubmed-meshheading:19724912-Animals,
pubmed-meshheading:19724912-Antigens, CD44,
pubmed-meshheading:19724912-Blotting, Western,
pubmed-meshheading:19724912-CDC2 Protein Kinase,
pubmed-meshheading:19724912-Calmodulin-Binding Proteins,
pubmed-meshheading:19724912-Carbazoles,
pubmed-meshheading:19724912-Cattle,
pubmed-meshheading:19724912-Cell Shape,
pubmed-meshheading:19724912-Cells, Cultured,
pubmed-meshheading:19724912-Endothelial Cells,
pubmed-meshheading:19724912-Epidermal Growth Factor,
pubmed-meshheading:19724912-Extracellular Matrix Proteins,
pubmed-meshheading:19724912-Fluorescent Antibody Technique,
pubmed-meshheading:19724912-Hyaluronic Acid,
pubmed-meshheading:19724912-Matrix Metalloproteinase 9,
pubmed-meshheading:19724912-Neovascularization, Physiologic,
pubmed-meshheading:19724912-Oligosaccharides,
pubmed-meshheading:19724912-Phosphorylation,
pubmed-meshheading:19724912-Protein Array Analysis,
pubmed-meshheading:19724912-Protein Kinase C-alpha,
pubmed-meshheading:19724912-Protein Kinase Inhibitors,
pubmed-meshheading:19724912-RNA, Small Interfering,
pubmed-meshheading:19724912-RNA Interference,
pubmed-meshheading:19724912-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19724912-Signal Transduction
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pubmed:year |
2009
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pubmed:articleTitle |
Oligosaccharides of hyaluronan induce angiogenesis through distinct CD44 and RHAMM-mediated signalling pathways involving Cdc2 and gamma-adducin.
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pubmed:affiliation |
School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester M1 5GD, UK.
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pubmed:publicationType |
Journal Article
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