Endothelial loss of Fzd5 stimulates PKC/Ets1-mediated transcription of Angpt2 and Flt1

Angiogenesis
Maarten M BrandtCaroline Cheng

Abstract

Formation of a functional vascular system is essential and its formation is a highly regulated process initiated during embryogenesis, which continues to play important roles throughout life in both health and disease. In previous studies, Fzd5 was shown to be critically involved in this process and here we investigated the molecular mechanism by which endothelial loss of this receptor attenuates angiogenesis. Using short interference RNA-mediated loss-of-function assays, the function and mechanism of signaling via Fzd5 was studied in human endothelial cells (ECs). Our findings indicate that Fzd5 signaling promotes neovessel formation in vitro in a collagen matrix-based 3D co-culture of primary vascular cells. Silencing of Fzd5 reduced EC proliferation, as a result of G0/G1 cell cycle arrest, and decreased cell migration. Furthermore, Fzd5 knockdown resulted in enhanced expression of the factors Angpt2 and Flt1, which are mainly known for their destabilizing effects on the vasculature. In Fzd5-silenced ECs, Angpt2 and Flt1 upregulation was induced by enhanced PKC signaling, without the involvement of canonical Wnt signaling, non-canonical Wnt/Ca2+-mediated activation of NFAT, and non-canonical Wnt/PCP-mediated activation of JNK...Continue Reading

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Citations

Jul 4, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Heleen M KoolRobbert J Rottier
Nov 4, 2020·Cancer Metastasis Reviews·Karlijn van LoonArjan W Griffioen
Jul 3, 2021·Frontiers in Immunology·Dorra Elhaj MahmoudLilia Laadhar
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Methods Mentioned

BETA
FCS
transfection
Protein Assay
electrophoresis
ELISA
PCR
fluorescence microscopy
confocal microscopy
flow cytometry
siSHAM

Software Mentioned

AngioSys
GraphPad Prism

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