Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII
- Soochow University, China
- Peking University, China
- University of Helsinki, Finland
- Institute of Basic Science and Korea Advanced Institute of Science and Technology, Republic of Korea
- Max-Planck-Institute for Molecular Biomedicine, Germany
Abstract
Mechanisms underlying the vein development remain largely unknown. Tie2 signaling mediates endothelial cell (EC) survival and vascular maturation and its activating mutations are linked to venous malformations. Here we show that vein formation are disrupted in mouse skin and mesentery when Tie2 signals are diminished by targeted deletion of Tek either ubiquitously or specifically in embryonic ECs. Postnatal Tie2 attenuation resulted in the degeneration of newly formed veins followed by the formation of haemangioma-like vascular tufts in retina and venous tortuosity. Mechanistically, Tie2 insufficiency compromised venous EC identity, as indicated by a significant decrease of COUP-TFII protein level, a key regulator in venogenesis. Consistently, angiopoietin-1 stimulation increased COUP-TFII in cultured ECs, while Tie2 knockdown or blockade of Tie2 downstream PI3K/Akt pathway reduced COUP-TFII which could be reverted by the proteasome inhibition. Together, our results imply that Tie2 is essential for venous specification and maintenance via Akt mediated stabilization of COUP-TFII.
Article and author information
Author details
Funding
National Natural Science Foundation of China (91539101,31271530,31071263)
- Yulong He
Ministry of Science and Technology of the People's Republic of China (2012CB947600)
- Yulong He
Priority Program Development of Jiangsu Higher Education Institutions
- Yulong He
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Elisabetta Dejana, FIRC Institute of Molecular Oncology, Italy
Ethics
Animal experimentation: Conditional mice with Tek gene targeted flox sites for gene deletion were generated by the National Resource Center for Mutant Mice, Nanjing University. All animal experiments were performed in accordance with the institutional guidelines of the Soochow and Nanjing University Animal Center (MARC-AP#YH2).
Version history
- Received: August 28, 2016
- Accepted: December 21, 2016
- Accepted Manuscript published: December 22, 2016 (version 1)
- Version of Record published: January 6, 2017 (version 2)
Copyright
© 2016, Chu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII
eLife 5:e21032.
https://doi.org/10.7554/eLife.21032
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