Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII
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 sign...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/21032 |
| id |
doaj-cfed42cfba284d59971714d7bf2ff36f |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Man Chu Taotao Li Bin Shen Xudong Cao Haoyu Zhong Luqing Zhang Fei Zhou Wenjuan Ma Haijuan Jiang Pancheng Xie Zhengzheng Liu Ningzheng Dong Ying Xu Yun Zhao Guoqiang Xu Peirong Lu Jincai Luo Qingyu Wu Kari Alitalo Gou Young Koh Ralf H Adams Yulong He |
| spellingShingle |
Man Chu Taotao Li Bin Shen Xudong Cao Haoyu Zhong Luqing Zhang Fei Zhou Wenjuan Ma Haijuan Jiang Pancheng Xie Zhengzheng Liu Ningzheng Dong Ying Xu Yun Zhao Guoqiang Xu Peirong Lu Jincai Luo Qingyu Wu Kari Alitalo Gou Young Koh Ralf H Adams Yulong He Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII eLife Tie2 COUP-TFII vein specification |
| author_facet |
Man Chu Taotao Li Bin Shen Xudong Cao Haoyu Zhong Luqing Zhang Fei Zhou Wenjuan Ma Haijuan Jiang Pancheng Xie Zhengzheng Liu Ningzheng Dong Ying Xu Yun Zhao Guoqiang Xu Peirong Lu Jincai Luo Qingyu Wu Kari Alitalo Gou Young Koh Ralf H Adams Yulong He |
| author_sort |
Man Chu |
| title |
Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII |
| title_short |
Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII |
| title_full |
Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII |
| title_fullStr |
Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII |
| title_full_unstemmed |
Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFII |
| title_sort |
angiopoietin receptor tie2 is required for vein specification and maintenance via regulating coup-tfii |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2016-12-01 |
| description |
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. |
| topic |
Tie2 COUP-TFII vein specification |
| url |
https://elifesciences.org/articles/21032 |
| work_keys_str_mv |
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1721476098327314432 |
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doaj-cfed42cfba284d59971714d7bf2ff36f2021-05-05T00:47:12ZengeLife Sciences Publications LtdeLife2050-084X2016-12-01510.7554/eLife.21032Angiopoietin receptor Tie2 is required for vein specification and maintenance via regulating COUP-TFIIMan Chu0Taotao Li1Bin Shen2Xudong Cao3Haoyu Zhong4Luqing Zhang5Fei Zhou6https://orcid.org/0000-0003-1857-8831Wenjuan Ma7Haijuan Jiang8Pancheng Xie9Zhengzheng Liu10Ningzheng Dong11Ying Xu12https://orcid.org/0000-0002-6689-7768Yun Zhao13Guoqiang Xu14Peirong Lu15Jincai Luo16Qingyu Wu17Kari Alitalo18Gou Young Koh19Ralf H Adams20Yulong He21https://orcid.org/0000-0002-0099-3749Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; MOE Key Laboratory for Model Animal and Disease Study, Model Animal Research Institute, Nanjing University, Nanjing, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; MOE Key Laboratory for Model Animal and Disease Study, Model Animal Research Institute, Nanjing University, Nanjing, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; MOE Key Laboratory for Model Animal and Disease Study, Model Animal Research Institute, Nanjing University, Nanjing, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCam-Su Genomic Resources Center, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, ChinaCam-Su Genomic Resources Center, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, ChinaCollege of Pharmaceutical Sciences, Soochow University, Suzhou, ChinaThe First Affiliated Hospital, Soochow University, Suzhou, ChinaLaboratory of Vascular Biology, Institute of Molecular Medicine, Peking University, Beijing, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, ChinaWihuri Research Institute and Translational Cancer Biology Center of Excellence, Biomedicum Helsinki University of Helsinki, Helsinki, FinlandCenter for Vascular Research, Institute of Basic Science and Korea Advanced Institute of Science and Technology (KAIST), Daejeon, KoreaMax-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, Faculty of Medicine, University of Münster, Münster, GermanyCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Cam-Su Genomic Resources Center, Soochow University, Suzhou, China; Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, ChinaMechanisms 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.https://elifesciences.org/articles/21032Tie2COUP-TFIIvein specification |