e-space
Manchester Metropolitan University's Research Repository

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

Deed, Richard and Rooney, Paul and Kumar, Patricia and Norton, John D. and Smith, Julia and Freemont, Anthony J. and Kumar, Shant (1997) Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan. International journal of cancer, 71 (2). pp. 251-6. ISSN 0020-7136

Full text not available from this repository.

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.

Impact and Reach

Statistics

Downloads
Activity Overview
0Downloads
228Hits

Additional statistics for this dataset are available via IRStats2.

Altmetric

Actions (login required)

View Item View Item