TY  - JOUR
AU  - Teichert, Martin
AU  - Milde, Laura
AU  - Holm, Annegret
AU  - Stanicek, Laura
AU  - Gengenbacher, Nicolas
AU  - Savant, Soniya
AU  - Ruckdeschel, Tina
AU  - Hasanov, Zulfiyya
AU  - Srivastava, Kshitij
AU  - Hu, Junhao
AU  - Hertel, Stella
AU  - Bartol, Arne
AU  - Schlereth, Katharina
AU  - Augustin, Hellmut G
TI  - Pericyte-expressed Tie2 controls angiogenesis and vessel maturation.
JO  - Nature Communications
VL  - 8
SN  - 2041-1723
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2017-01436
SP  - 16106 -
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28719590
C2  - pmc:PMC5520106
DO  - DOI:10.1038/ncomms16106
UR  - https://inrepo02.dkfz.de/record/125298
ER  -