Human peroxidasin 1 promotes angiogenesis through ERK1/2, Akt and FAK pathways

[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.

Disciplines :

Oncology

Author, co-author :

Medfai, Hayfa

Khalil, Alia

Rousseau, Alexandre

Nuyens, Vincent

Paumann-Page, Martina

Sevcnikar, Benjamin

Furtmüller, Paul

Obinger, Christian

Moguilevsky, Nicole

Peulen, Olivier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques

More authors (6 more)

Language :

English

Title :

Human peroxidasin 1 promotes angiogenesis through ERK1/2, Akt and FAK pathways

Publication date :

2019

Journal title :

Cardiovascular Research

ISSN :

0008-6363

eISSN :

1755-3245

Publisher :

Elsevier, Netherlands

Volume :

115(2)

Pages :

463-475

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 29 June 2018

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