Reference : Human peroxidasin 1 promotes angiogenesis through ERK1/2, Akt and FAK pathways
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/226095
Human peroxidasin 1 promotes angiogenesis through ERK1/2, Akt and FAK pathways
English
Medfai, Hayfa []
Khalil, Alia []
Rousseau, Alexandre []
Nuyens, Vincent []
Paumann-Page, Martina []
Sevcnikar, Benjamin []
Furtmüller, Paul []
Obinger, Christian []
Moguilevsky, Nicole []
Peulen, Olivier mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Herfs, Michael mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Castronovo, Vincenzo mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Amri, Mohammed []
Van Antwerpen, Pierre []
Vanhamme, Luc []
Zouaoui Boudjeltia, Karim []
In press
Cardiovascular Research
Elsevier
Yes (verified by ORBi)
International
0008-6363
Netherlands
[en] Human peroxidasin 1 ; Angiogenesis ; Extracellular-signal-regulated kinase 1/2 ; Akt ; Focal adhesion kinase
[en] The term angiogenesis refers to sprouting of new blood vessels from pre-existing ones. The angiogenic process involves cell migration and tubulogenesis requiring interaction between endothelial cells and the extracellular ma- trix. Human peroxidasin 1 (hsPxd01) is a multidomain heme peroxidase found embedded in the basement mem- branes. As it promotes the stabilization of extracellular matrix, we investigated its possible role in angiogenesis
both in vitro and in vivo.
We analysed the effects of peroxidasin 1 gene silencing and supplementation by recombinant hsPxd01 in
TeloHAEC endothelial cells on cell migration, tubulogenesis in matrigel, and intracellular signal transduction as
assessed by kinase phosphorylation and expression of pro-angiogenic genes as measured by qRT–PCR. We further
evaluated the angiogenic potential of recombinant peroxidasin in a chicken chorioallantoic membrane model. RNA
silencing of endogenous hsPxd01 significantly reduced tube formation and cell migration, whereas supplementation
by the recombinant peroxidase promoted tube formation in vitro and stimulated vascularization in vivo through its
catalytic activity. Moreover, recombinant hsPxd01 promoted phosphorylation of Extracellular signal-Regulated
Kinases (ERK1/2), Protein kinase B (Akt), and Focal Adhesion Kinase (FAK), and induced the expression of pro-
angiogenic downstream genes: Platelet Derived Growth Factor Subunit B (PDGFB), endothelial-derived Heparin
Binding EGF-like growth factor (HB-EGF), CXCL-1, Hairy-Related Transcription Factor 1 (HEY-1), DNA-binding
protein inhibitor (ID-2), Snail Family Zinc Finger 1 (SNAI-1), as well as endogenous hsPxd01. However, peroxidasin
silencing significantly reduced Akt and FAK phosphorylation but induced ERK1/2 activation after supplementation
by recombinant hsPxd01. While hsPxd01 silencing significantly reduced expression of HEY-1, ID-2, and PDGFB, it
did not affect expression of SNAI-1, HB-EGF, and CXCL-1 after supplementation by recombinant hsPxd01.
Our findings suggest a role of enzymatically active peroxidasin 1 as a pro-angiogenic peroxidase and a modulator of ERK1/2, Akt and FAK signalling.
Researchers
http://hdl.handle.net/2268/226095
10.1093/cvr/cvy179

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