Pericyte-expressed Tie2 controls angiogenesis and vessel maturation.

Abstract:

:The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through its supposed endothelial-specific expression. Yet, Tie2 is also expressed at lower levels by pericytes and it has not been unravelled through which mechanisms pericyte Angiopoietin/Tie signalling affects angiogenesis. Here we show that human and murine pericytes express functional Tie2 receptor. Silencing of Tie2 in pericytes results in a pro-migratory phenotype. Pericyte Tie2 controls sprouting angiogenesis in in vitro sprouting and in vivo spheroid assays. Tie2 downstream signalling in pericytes involves Calpain, Akt and FOXO3A. Ng2-Cre-driven deletion of pericyte-expressed Tie2 in mice transiently delays postnatal retinal angiogenesis. Yet, Tie2 deletion in pericytes results in a pronounced pro-angiogenic effect leading to enhanced tumour growth. Together, the data expand and revise the current concepts on vascular Angiopoietin/Tie signalling and propose a bidirectional, reciprocal EC-pericyte model of Tie2 signalling.

journal_name

Nat Commun

journal_title

Nature communications

authors

Teichert M,Milde L,Holm A,Stanicek L,Gengenbacher N,Savant S,Ruckdeschel T,Hasanov Z,Srivastava K,Hu J,Hertel S,Bartol A,Schlereth K,Augustin HG

doi

10.1038/ncomms16106

subject

Has Abstract

pub_date

2017-07-18 00:00:00

pages

16106

issn

2041-1723

pii

ncomms16106

journal_volume

8

pub_type

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