Pericyte-expressed Tie2 controls angiogenesis and vessel maturation

Martin Teichert, Laura Milde, Annegret Holm, Laura Stanicek, Nicolas Gengenbacher, Soniya Savant, Tina Ruckdeschel, Zulfiyya Hasanov, Kshitij Srivastava, Junhao Hu, Stella Hertel, Arne Bartol, Katharina Schlereth and Hellmut G. Augustin ()
Additional contact information
Martin Teichert: German Cancer Research Center (DKFZ-ZMBH Alliance)
Laura Milde: German Cancer Research Center (DKFZ-ZMBH Alliance)
Annegret Holm: German Cancer Research Center (DKFZ-ZMBH Alliance)
Laura Stanicek: German Cancer Research Center (DKFZ-ZMBH Alliance)
Nicolas Gengenbacher: German Cancer Research Center (DKFZ-ZMBH Alliance)
Soniya Savant: German Cancer Research Center (DKFZ-ZMBH Alliance)
Tina Ruckdeschel: German Cancer Research Center (DKFZ-ZMBH Alliance)
Zulfiyya Hasanov: German Cancer Research Center (DKFZ-ZMBH Alliance)
Kshitij Srivastava: German Cancer Research Center (DKFZ-ZMBH Alliance)
Junhao Hu: German Cancer Research Center (DKFZ-ZMBH Alliance)
Stella Hertel: German Cancer Research Center (DKFZ-ZMBH Alliance)
Arne Bartol: German Cancer Research Center (DKFZ-ZMBH Alliance)
Katharina Schlereth: German Cancer Research Center (DKFZ-ZMBH Alliance)
Hellmut G. Augustin: German Cancer Research Center (DKFZ-ZMBH Alliance)

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms16106

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