Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis

Bauer, Andrea; Mylroie, Hayley; Thornton, C. Clare; Calay, Damien; Birdsey, Graeme M.; Kiprianos, Allan P.; Wilson, Garrick K.; Soares, Miguel P.; Yin, Xiaoke; Mayr, Manuel; Randi, Anna M.; Mason, Justin C.

Publication

Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis

2016-07-08Journal article

dc.contributor.author	Bauer, Andrea
dc.contributor.author	Mylroie, Hayley
dc.contributor.author	Thornton, C. Clare
dc.contributor.author	Calay, Damien
dc.contributor.author	Birdsey, Graeme M.
dc.contributor.author	Kiprianos, Allan P.
dc.contributor.author	Wilson, Garrick K.
dc.contributor.author	Soares, Miguel P.
dc.contributor.author	Yin, Xiaoke
dc.contributor.author	Mayr, Manuel
dc.contributor.author	Randi, Anna M.
dc.contributor.author	Mason, Justin C.
dc.date.accessioned	2016-07-11T15:08:22Z
dc.date.available	2016-07-11T15:08:22Z
dc.date.issued	2016-07-08
dc.description.abstract	Angiogenesis is an essential physiological process and an important factor in disease pathogenesis. However, its exploitation as a clinical target has achieved limited success and novel molecular targets are required. Although heme oxygenase-1 (HO-1) acts downstream of vascular endothelial growth factor (VEGF) to modulate angiogenesis, knowledge of the mechanisms involved remains limited. We set out identify novel HO-1 targets involved in angiogenesis. HO-1 depletion attenuated VEGF-induced human endothelial cell (EC) proliferation and tube formation. The latter response suggested a role for HO-1 in EC migration, and indeed HO-1 siRNA negatively affected directional migration of EC towards VEGF; a phenotype reversed by HO-1 over-expression. EC from Hmox1(-/-) mice behaved similarly. Microarray analysis of HO-1-depleted and control EC exposed to VEGF identified cyclins A1 and E1 as HO-1 targets. Migrating HO-1-deficient EC showed increased p27, reduced cyclin A1 and attenuated cyclin-dependent kinase 2 activity. In vivo, cyclin A1 siRNA inhibited VEGF-driven angiogenesis, a response reversed by Ad-HO-1. Proteomics identified structural protein vimentin as an additional VEGF-HO-1 target. HO-1 depletion inhibited VEGF-induced calpain activity and vimentin cleavage, while vimentin silencing attenuated HO-1-driven proliferation. Thus, vimentin and cyclins A1 and E1 represent VEGF-activated HO-1-dependent targets important for VEGF-driven angiogenesis.	pt_PT
dc.description.sponsorship	National Heart and Lung Institute Foundation UK charity studentship: (Charity no. 1048073); National Institute for Health Research (NIHR); Biomedical Research Centre; Imperial College Healthcare NHS; Trust and Imperial College London.	pt_PT
dc.identifier.citation	Bauer, A. et al. Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis. Sci. Rep. 6, 29417; doi: 10.1038/srep29417 (2016).	pt_PT
dc.identifier.doi	10.1038/srep29417	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.7/680
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Nature Publishing Group	pt_PT
dc.relation.publisherversion	http://www.nature.com/articles/srep29417#additional-information	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	Cell migration	pt_PT
dc.subject	cell signalling	pt_PT
dc.title	Identification of cyclins A1, E1 and vimentin as downstream targets of heme oxygenase-1 in vascular endothelial growth factor-mediated angiogenesis	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.endPage	1	pt_PT
oaire.citation.issue	16	pt_PT
oaire.citation.startPage	29417	pt_PT
oaire.citation.title	Scientific Reports	pt_PT
oaire.citation.volume	6	pt_PT
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT