Yes-Associated Protein Promotes Angiogenesis via Signal Transducer and Activator of Transcription 3 in Endothelial Cells

doi:10.1161/CIRCRESAHA.117.311950

. 2018 Feb 16;122(4):591-605.

doi: 10.1161/CIRCRESAHA.117.311950. Epub 2018 Jan 3.

Yes-Associated Protein Promotes Angiogenesis via Signal Transducer and Activator of Transcription 3 in Endothelial Cells

Jinlong He¹, Qiankun Bao¹, Yan Zhang¹, Mingming Liu¹, Huizhen Lv¹, Yajin Liu¹, Liu Yao¹, Bochuan Li¹, Chenghu Zhang¹, Shuang He¹, Guijin Zhai¹, Yan Zhu¹, Xin Liu¹, Kai Zhang¹, Xiu-Jie Wang¹, Ming-Hui Zou¹, Yi Zhu¹, Ding Ai²

Affiliations

¹ From the Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology (J.H., Q.B., M.L., H.L., Y.L., L.Y., B.L., C.Z., G.Z., K.Z., Y.Z., D.A.) and College of Optometry and Ophthalmology, Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute (Y.Z.), Tianjin Medical University, China; Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine (S.H., Y.Z.); Key Laboratory of Network Genetics, Collaborative Innovation Center for Cardiovascular Disorders, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing (X.L., X.-J.W.); Center for Molecular and Translational Medicine, Georgia State University, Atlanta (M.-H.Z.); and Tianjin Key Laboratory of Metabolic Diseases, China (Y.Z., D.A.).
² From the Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology (J.H., Q.B., M.L., H.L., Y.L., L.Y., B.L., C.Z., G.Z., K.Z., Y.Z., D.A.) and College of Optometry and Ophthalmology, Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute (Y.Z.), Tianjin Medical University, China; Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine (S.H., Y.Z.); Key Laboratory of Network Genetics, Collaborative Innovation Center for Cardiovascular Disorders, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing (X.L., X.-J.W.); Center for Molecular and Translational Medicine, Georgia State University, Atlanta (M.-H.Z.); and Tianjin Key Laboratory of Metabolic Diseases, China (Y.Z., D.A.). edin2000cn@gmail.com.

PMID: 29298775
DOI: 10.1161/CIRCRESAHA.117.311950

Yes-Associated Protein Promotes Angiogenesis via Signal Transducer and Activator of Transcription 3 in Endothelial Cells

Jinlong He et al. Circ Res. 2018.

. 2018 Feb 16;122(4):591-605.

doi: 10.1161/CIRCRESAHA.117.311950. Epub 2018 Jan 3.

Authors

Affiliations

¹ From the Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology (J.H., Q.B., M.L., H.L., Y.L., L.Y., B.L., C.Z., G.Z., K.Z., Y.Z., D.A.) and College of Optometry and Ophthalmology, Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute (Y.Z.), Tianjin Medical University, China; Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine (S.H., Y.Z.); Key Laboratory of Network Genetics, Collaborative Innovation Center for Cardiovascular Disorders, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing (X.L., X.-J.W.); Center for Molecular and Translational Medicine, Georgia State University, Atlanta (M.-H.Z.); and Tianjin Key Laboratory of Metabolic Diseases, China (Y.Z., D.A.).
² From the Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology (J.H., Q.B., M.L., H.L., Y.L., L.Y., B.L., C.Z., G.Z., K.Z., Y.Z., D.A.) and College of Optometry and Ophthalmology, Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute (Y.Z.), Tianjin Medical University, China; Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine (S.H., Y.Z.); Key Laboratory of Network Genetics, Collaborative Innovation Center for Cardiovascular Disorders, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing (X.L., X.-J.W.); Center for Molecular and Translational Medicine, Georgia State University, Atlanta (M.-H.Z.); and Tianjin Key Laboratory of Metabolic Diseases, China (Y.Z., D.A.). edin2000cn@gmail.com.

PMID: 29298775
DOI: 10.1161/CIRCRESAHA.117.311950

Erratum in

Correction to: Yes-Associated Protein Promotes Angiogenesis via Signal Transducer and Activator of Transcription 3 in Endothelial Cells.
[No authors listed] [No authors listed] Circ Res. 2019 Sep 13;125(7):e32. doi: 10.1161/RES.0000000000000298. Epub 2019 Sep 12. Circ Res. 2019. PMID: 31513486 No abstract available.

Abstract

Rationale: Angiogenesis is a complex process regulating endothelial cell (EC) functions. Emerging lines of evidence support that YAP (Yes-associated protein) plays an important role in regulating the angiogenic activity of ECs.

Objective: The objective of this study was to specify the effect of EC YAP on angiogenesis and its underlying mechanisms.

Method and results: In ECs, vascular endothelial growth factor reduced YAP phosphorylation time and dose dependently and increased its nuclear accumulation. Using Tie2Cre-mediated YAP transgenic mice, we found that YAP promoted angiogenesis in the postnatal retina and tumor tissues. Mass spectrometry revealed signal transducer and activator of transcription 3 (STAT3) as a potential binding partner of YAP in ECs. Western blot and immunoprecipitation assays indicated that binding with YAP prolonged interleukin 6-induced STAT3 nuclear accumulation by blocking chromosomal maintenance 1-mediated STAT3 nuclear export without affecting its phosphorylation. Moreover, angiopoietin-2 expression induced by STAT3 was enhanced by YAP overexpression in ECs. Finally, a selective STAT3 inhibitor or angiopoietin-2 blockage partly attenuated retinal angiogenesis in Tie2Cre-mediated YAP transgenic mice.

Conclusions: YAP binding sustained STAT3 in the nucleus to enhance the latter's transcriptional activity and promote angiogenesis via regulation of angiopoietin-2.

Keywords: STAT3 transcription factor; angiopoietin-2; endothelial cells; vascular endothelial growth factor A.

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Yes-Associated Protein Promotes Angiogenesis via Signal Transducer and Activator of Transcription 3 in Endothelial Cells

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Yes-Associated Protein Promotes Angiogenesis via Signal Transducer and Activator of Transcription 3 in Endothelial Cells

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