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 Communjournal_title
Nature communicationsauthors
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 HGdoi
10.1038/ncomms16106subject
Has Abstractpub_date
2017-07-18 00:00:00pages
16106issn
2041-1723pii
ncomms16106journal_volume
8pub_type
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