Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95472
Title:
Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan.
Authors:
Deed, Richard W; Rooney, P; Kumar, Patricia; Norton, John D; Smith, J; Freemont, A J; Kumar, Shant
Abstract:
The degradation products of hyaluronan are known to stimulate endothelial-cell proliferation and to promote neovascularization associated with angiogenesis, whilst native high-molecular-weight hyaluronan is inhibitory to these processes. To investigate the cellular signalling pathways coupled to hyaluronan-induced responses in angiogenesis, we have analyzed early-response gene expression in vitro, in cultured bovine aortic endothelial cells. Angiogenic oligosaccharides of hyaluronan induced rapid transient up-regulation of the immediate early genes c-fos, c-jun, jun-B, Krox-20 and Krox-24. In contrast, native hyaluronan when used alone failed to elicit a significant change in expression of any of the genes tested, and when used in combination with angiogenic oligosaccharides of hyaluronan, gave a dose-dependent inhibition of induced gene expression. However, prior addition of angiogenic hyaluronan, as little as one minute before addition of high-molecular-weight hyaluronan, abrogated this inhibition, suggesting that positive or negative responses associated with hyaluronan signalling are integrated at a very early stage following receptor binding. Conversely, prior addition of high-molecular-weight hyaluronan led to an irreversible block in gene expression and proliferative response. These data are consistent with native hyaluronan antagonizing the angiogenic response in part by blocking a signalling cascade at or immediately following ligand-receptor interaction. Finally, we demonstrated that chronic exposure to oligosaccharides of hyaluronan is essential for cell proliferation, indicating that short-term immediate early-gene signalling is insufficient to elicit the proliferation of endothelial cells.
Affiliation:
Paterson Institute for Cancer Research, Manchester, UK.
Citation:
Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan. 1997, 71 (2):251-6 Int. J. Cancer
Journal:
International Journal of Cancer
Issue Date:
10-Apr-1997
URI:
http://hdl.handle.net/10541/95472
DOI:
10.1002/(SICI)1097-0215(19970410)71:2<251::AID-IJC21>3.0.CO;2-J
PubMed ID:
9139851
Type:
Article
Language:
en
ISSN:
0020-7136
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDeed, Richard Wen
dc.contributor.authorRooney, Pen
dc.contributor.authorKumar, Patriciaen
dc.contributor.authorNorton, John Den
dc.contributor.authorSmith, Jen
dc.contributor.authorFreemont, A Jen
dc.contributor.authorKumar, Shanten
dc.date.accessioned2010-04-01T13:32:46Z-
dc.date.available2010-04-01T13:32:46Z-
dc.date.issued1997-04-10-
dc.identifier.citationEarly-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan. 1997, 71 (2):251-6 Int. J. Canceren
dc.identifier.issn0020-7136-
dc.identifier.pmid9139851-
dc.identifier.doi10.1002/(SICI)1097-0215(19970410)71:2<251::AID-IJC21>3.0.CO;2-J-
dc.identifier.urihttp://hdl.handle.net/10541/95472-
dc.description.abstractThe degradation products of hyaluronan are known to stimulate endothelial-cell proliferation and to promote neovascularization associated with angiogenesis, whilst native high-molecular-weight hyaluronan is inhibitory to these processes. To investigate the cellular signalling pathways coupled to hyaluronan-induced responses in angiogenesis, we have analyzed early-response gene expression in vitro, in cultured bovine aortic endothelial cells. Angiogenic oligosaccharides of hyaluronan induced rapid transient up-regulation of the immediate early genes c-fos, c-jun, jun-B, Krox-20 and Krox-24. In contrast, native hyaluronan when used alone failed to elicit a significant change in expression of any of the genes tested, and when used in combination with angiogenic oligosaccharides of hyaluronan, gave a dose-dependent inhibition of induced gene expression. However, prior addition of angiogenic hyaluronan, as little as one minute before addition of high-molecular-weight hyaluronan, abrogated this inhibition, suggesting that positive or negative responses associated with hyaluronan signalling are integrated at a very early stage following receptor binding. Conversely, prior addition of high-molecular-weight hyaluronan led to an irreversible block in gene expression and proliferative response. These data are consistent with native hyaluronan antagonizing the angiogenic response in part by blocking a signalling cascade at or immediately following ligand-receptor interaction. Finally, we demonstrated that chronic exposure to oligosaccharides of hyaluronan is essential for cell proliferation, indicating that short-term immediate early-gene signalling is insufficient to elicit the proliferation of endothelial cells.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAntigens, CD44-
dc.subject.meshCattle-
dc.subject.meshCell Division-
dc.subject.meshCells, Cultured-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshEarly Growth Response Protein 2-
dc.subject.meshEndothelium, Vascular-
dc.subject.meshGene Expression Regulation-
dc.subject.meshHyaluronic Acid-
dc.subject.meshImmediate-Early Proteins-
dc.subject.meshImmunohistochemistry-
dc.subject.meshNeovascularization, Physiologic-
dc.subject.meshProto-Oncogene Proteins c-fos-
dc.subject.meshProto-Oncogene Proteins c-jun-
dc.subject.meshTranscription Factors-
dc.subject.meshUp-Regulation-
dc.titleEarly-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalInternational Journal of Canceren
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