Skip to main content
main-content

29.05.2018 | Original Paper | Ausgabe 4/2018 Open Access

Angiogenesis 4/2018

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

Zeitschrift:
Angiogenesis > Ausgabe 4/2018
Autoren:
Maarten M. Brandt, Christian G. M. van Dijk, Ihsan Chrifi, Heleen M. Kool, Petra E. Bürgisser, Laura Louzao-Martinez, Jiayi Pei, Robbert J. Rottier, Marianne C. Verhaar, Dirk J. Duncker, Caroline Cheng
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10456-018-9625-6) contains supplementary material, which is available to authorized users.

Abstract

Aims

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.

Methods and results

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. We demonstrated that PKC-induced transcription of Angpt2 and Flt1 involved the transcription factor Ets1.

Conclusions

The current study demonstrates a pro-angiogenic role of Fzd5, which was shown to be involved in endothelial tubule formation, cell cycle progression and migration, and partly does so by repression of PKC/Ets1-mediated transcription of Flt1 and Angpt2.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

e.Med Innere Medizin

Kombi-Abonnement

Mit e.Med Innere Medizin erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Innere Medizin, den Premium-Inhalten der internistischen Fachzeitschriften, inklusive einer gedruckten internistischen Zeitschrift Ihrer Wahl.

e.Med Chirurgie

Kombi-Abonnement

Mit e.Med Chirurgie erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Chirurgie, den Premium-Inhalten der chirurgischen Fachzeitschriften, inklusive einer gedruckten chirurgischen Zeitschrift Ihrer Wahl.

Zusatzmaterial
Supplementary material 1 (DOCX 2907 KB)
10456_2018_9625_MOESM1_ESM.docx
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 4/2018

Angiogenesis 4/2018 Zur Ausgabe

Neu im Fachgebiet Kardiologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Kardiologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise