Redox-dependent stimulation of angiogenesis and tissue repair by pentose phosphate derivatives: an alternative to pro-angiogenic growth factors?
|Starts:||14:00 17 Oct 2014|
|Ends:||15:00 17 Oct 2014|
|What is it:||Seminar|
|Organiser:||Faculty of Life Sciences|
|Who is it for:||University staff, Current University students|
This seminar is part of the Manchester Tissue Regeneration & Stem Cell Network seminar series. Redox-dependent regulation of angiogenesis is an important and emerging topic in vascular sciences. Modulations in the levels of reactive oxygen species (ROS) generation have been shown to play a critical role in the stimulation of the angiogenic response in vivo and in the modulation of vascular endothelial cell proliferation and migration in vitro. In this study, we uncovered the link between the pro-angiogenic activity of deoxyribose-1-phosphate (dRP) and other pentose phosphate molecules (i.e. deoxyribose-5-phospate (dR5P), ribose-1-phosphate (R1P)) and the effect of these molecules on endothelial cell redox state. We demonstrated that endothelial cell treatment with dRP, dR5P and R1P induces the activation of NADP oxidases (NOXs) and stimulates a sharp increase in the superoxide anion generation rate. The oxidative stress induced by physiological levels of these molecules was shown to activate the redox-sensitive transcription factor NF-kB and to initiate profound changes in the physiology of endothelial cells, which include the upregulation of adhesion molecules (e.g. integrin ?3), anti-apoptotic molecules (e.g. Bcl-2) and pro-angiogenic effectors (e.g. VEGFR2). Especially the upregulation of VEGFR2 and the sensitisation of the VEGF pathway appeared to be crucial for the stimulation of the pro-angiogenic responses stimulated by pentose phosphates. Functionally, endothelial cell treatment with pentose phosphates in vitro resulted in a significant increase in cell migration rates and tubulogenic activity in 3D cell cultures, while the administration of dRP in vivo stimulated tissue vascularisation and accelerated wound healing. Taken together, we propose that dRP and other chemically-related pentose phosphates are novel and convenient pro-angiogenic molecules and we advocate their study for regenerative medicine purposes.
Organisation: University of Bath
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