Pericyte-expressed Tie2 controls angiogenesis and vessel maturation

Nat Commun. 2017 Jul 18;8:16106. doi: 10.1038/ncomms16106.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, SCID
  • Neovascularization, Pathologic*
  • Neovascularization, Physiologic*
  • Pericytes / metabolism*
  • Receptor, TIE-2 / metabolism*
  • Ribonuclease, Pancreatic / metabolism

Substances

  • Receptor, TIE-2
  • TEK protein, human
  • Tek protein, mouse
  • Ang2 protein, mouse
  • Ribonuclease, Pancreatic