Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII

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http://hdl.handle.net/10138/177628

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Chu , M , Li , T , Shen , B , Cao , X , Zhong , H , Zhang , L , Zhou , F , Ma , W , Jiang , H , Xie , P , Liu , Z , Dong , N , Xu , Y , Zhao , Y , Xu , G , Lu , P , Luo , J , Wu , Q , Alitalo , K , Koh , G Y , Adams , R H & He , Y 2016 , ' Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII ' , eLife , vol. 5 , 21032 . https://doi.org/10.7554/eLife.21032

Title: Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII
Author: Chu, Man; Li, Taotao; Shen, Bin; Cao, Xudong; Zhong, Haoyu; Zhang, Luqing; Zhou, Fei; Ma, Wenjuan; Jiang, Haijuan; Xie, Pancheng; Liu, Zhengzheng; Dong, Ningzheng; Xu, Ying; Zhao, Yun; Xu, Guoqiang; Lu, Peirong; Luo, Jincai; Wu, Qingyu; Alitalo, Kari; Koh, Gou Young; Adams, Ralf H.; He, Yulong
Contributor: University of Helsinki, Research Programs Unit
Date: 2016-12-22
Language: eng
Number of pages: 16
Belongs to series: eLife
ISSN: 2050-084X
URI: http://hdl.handle.net/10138/177628
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.
Subject: ARTERIAL SPECIFICATION
VENOUS DIFFERENTIATION
VASCULAR DEVELOPMENT
TYROSINE KINASES
TIP CELLS
MOUSE
ANGIOGENESIS
EXPRESSION
PATHWAY
MICE
3111 Biomedicine
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