Universität zu Köln

Teichert, Martin, Milde, Laura, Holm, Annegret, Stanicek, Laura, Gengenbacher, Nicolas, Savant, Soniya, Ruckdeschel, Tina, Hasanov, Zulfiyya, Srivastava, Kshitij, Hu, Junhao, Hertel, Stella, Bartol, Arne, Schlereth, Katharina and Augustin, Hellmut G. (2017). Pericyte-expressed Tie2 controls angiogenesis and vessel maturation. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Teichert, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Milde, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Holm, Annegret UNSPECIFIED UNSPECIFIED UNSPECIFIED Stanicek, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Gengenbacher, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED Savant, Soniya UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruckdeschel, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hasanov, Zulfiyya UNSPECIFIED UNSPECIFIED UNSPECIFIED Srivastava, Kshitij UNSPECIFIED UNSPECIFIED UNSPECIFIED Hu, Junhao UNSPECIFIED UNSPECIFIED UNSPECIFIED Hertel, Stella UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartol, Arne UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlereth, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Augustin, Hellmut G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-224929
DOI:	10.1038/ncomms16106
Journal or Publication Title:	Nat. Commun.
Volume:	8
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RECEPTOR TYROSINE KINASE; ENDOTHELIAL-CELLS; DIABETIC-RETINOPATHY; ANGIOPOIETIN-2; HYPOXIA; BLOOD; MOUSE; LYMPHANGIOGENESIS; IDENTIFICATION; MORPHOGENESIS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22492