Histone Deacetylase 7 Controls Endothelial Cell Growth Through Modulation of β-Catenin
| العنوان: | Histone Deacetylase 7 Controls Endothelial Cell Growth Through Modulation of β-Catenin |
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| المؤلفون: | Eirini Karamariti, Hongling Li, Yanhua Hu, Anna Zampetaki, Lingfang Zeng, Qingbo Xu, Gillian W. Cockerill, Xiaoke Yin, Manuel Mayr, Elena De Falco, Zhongyi Zhang, Qingzhong Xiao, Daniel Martin, Andriana Margariti, Boda Zhou |
| المصدر: | Circulation Research. 106:1202-1211 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Time Factors, Physiology, Genetic Vectors, Active Transport, Cell Nucleus, Neovascularization, Physiologic, Biology, Histone Deacetylases, Mass Spectrometry, Adenoviridae, Cyclin D1, E2F2 Transcription Factor, Transduction, Genetic, Cyclin E, Humans, Immunoprecipitation, Cells, Cultured, beta Catenin, Cell Proliferation, Inhibitor of Differentiation Protein 2, E2F2, Oncogene Proteins, Phospholipase C gamma, Reverse Transcriptase Polymerase Chain Reaction, Cell Cycle, Endothelial Cells, HDAC7, Hypertrophy, Molecular biology, Phosphotransferases (Alcohol Group Acceptor), Cyclin E1, Vascular endothelial growth factor A, 14-3-3 Proteins, Vascular endothelial growth factor C, RNA Interference, Human umbilical vein endothelial cell, Histone deacetylase, Cardiology and Cardiovascular Medicine, Protein Processing, Post-Translational, Protein Binding, Signal Transduction |
| الوصف: | Rationale : Histone deacetylase (HDAC)7 is expressed in the early stages of embryonic development and may play a role in endothelial function. Objective : This study aimed to investigate the role of HDAC7 in endothelial cell (EC) proliferation and growth and the underlying mechanism. Methods and Results : Overexpression of HDAC7 by adenoviral gene transfer suppressed human umbilical vein endothelial cell (HUVEC) proliferation by preventing nuclear translocation of β-catenin and downregulation of T-cell factor-1/Id2 (inhibitor of DNA binding 2) and cyclin D1, leading to G 1 phase elongation. Further assays with the TOPFLASH reporter and quantitative RT-PCR for other β-catenin target genes such as Axin2 confirmed that overexpression of HDAC7 decreased β-catenin activity. Knockdown of HDAC7 by lentiviral short hairpin RNA transfer induced β-catenin nuclear translocation but downregulated cyclin D1, cyclin E1 and E2F2, causing HUVEC hypertrophy. Immunoprecipitation assay and mass spectrometry analysis revealed that HDAC7 directly binds to β-catenin and forms a complex with 14-3-3 ε, ζ, and η proteins. Vascular endothelial growth factor treatment induced HDAC7 degradation via PLCγ-IP3K (phospholipase Cγ–inositol-1,4,5-trisphosphate kinase) signal pathway and partially rescued HDAC7-mediated suppression of proliferation. Moreover, vascular endothelial growth factor stimulation suppressed the binding of HDAC7 with β-catenin, disrupting the complex and releasing β-catenin to translocate into the nucleus. Conclusions : These findings demonstrate that HDAC7 interacts with β-catenin keeping ECs in a low proliferation stage and provides a novel insight into the mechanism of HDAC7-mediated signal pathways leading to endothelial growth. |
| تدمد: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.109.213165 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab7ac613d842139f45637813e1109d0e https://doi.org/10.1161/circresaha.109.213165 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ab7ac613d842139f45637813e1109d0e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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| DOI: | 10.1161/circresaha.109.213165 |