Erschienen:
Springer Science and Business Media LLC, 2017
Erschienen in:Nature Communications
Sprache:
Englisch
DOI:
10.1038/ncomms16106
ISSN:
2041-1723
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>in vitro</jats:italic> sprouting and <jats:italic>in vivo</jats:italic> spheroid assays. Tie2 downstream signalling in pericytes involves Calpain, Akt and FOXO3A. <jats:italic>Ng2-Cre</jats:italic>-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.</jats:p>