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Pericyte-expressed Tie2 controls angiogenesis and vessel maturation

Author

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  • Martin Teichert

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Present address: GE Healthcare, SE-751 84 Uppsala, Sweden)

  • Laura Milde

    (German Cancer Research Center (DKFZ-ZMBH Alliance))

  • Annegret Holm

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Present address: Clinic for Paediatrics, University of Cologne, D-50924 Cologne, Germany)

  • Laura Stanicek

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Present address: Institute of Cardiovascular Regeneration, University of Frankfurt, D-60590 Frankfurt, Germany)

  • Nicolas Gengenbacher

    (German Cancer Research Center (DKFZ-ZMBH Alliance))

  • Soniya Savant

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Medical Faculty Mannheim, Heidelberg University
    Present address: Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden)

  • Tina Ruckdeschel

    (German Cancer Research Center (DKFZ-ZMBH Alliance))

  • Zulfiyya Hasanov

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Medical Faculty Mannheim, Heidelberg University)

  • Kshitij Srivastava

    (German Cancer Research Center (DKFZ-ZMBH Alliance))

  • Junhao Hu

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Present address: Interdisciplinary Research Center on Biology and Chemistry, Chinese Academy of Sciences, CN-200031 Shanghai, China)

  • Stella Hertel

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Medical Faculty Mannheim, Heidelberg University)

  • Arne Bartol

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Medical Faculty Mannheim, Heidelberg University)

  • Katharina Schlereth

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Medical Faculty Mannheim, Heidelberg University)

  • Hellmut G. Augustin

    (German Cancer Research Center (DKFZ-ZMBH Alliance)
    Medical Faculty Mannheim, Heidelberg University)

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.

Suggested Citation

  • Martin Teichert & Laura Milde & Annegret Holm & Laura Stanicek & Nicolas Gengenbacher & Soniya Savant & Tina Ruckdeschel & Zulfiyya Hasanov & Kshitij Srivastava & Junhao Hu & Stella Hertel & Arne Bart, 2017. "Pericyte-expressed Tie2 controls angiogenesis and vessel maturation," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16106
    DOI: 10.1038/ncomms16106
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    Cited by:

    1. Qiuxia Li & Quanjiang Zhang & Young-Rae Kim & Ravinder Reddy Gaddam & Julia S. Jacobs & Markus M. Bachschmid & Tsneem Younis & Zhiyong Zhu & Leonid Zingman & Barry London & Adam J. Rauckhorst & Eric B, 2023. "Deficiency of endothelial sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Gyunghee Jo & Jeomil Bae & Ho Jeong Hong & Ah-reum Han & Do-Kyun Kim & Seon Pyo Hong & Jung A Kim & Sangkyu Lee & Gou Young Koh & Ho Min Kim, 2021. "Structural insights into the clustering and activation of Tie2 receptor mediated by Tie2 agonistic antibody," Nature Communications, Nature, vol. 12(1), pages 1-18, December.

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