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DOI | 10.1038/s41467-019-11652-5 |
Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells | |
Das, Sadhan1; Senapati, Parijat1; Chen, Zhuo1; Reddy, Marpadga A.1; Ganguly, Rituparna1; Lanting, Linda1; Mandi, Varun1; Bansal, Anita1; Leung, Amy1; Zhang, Selena1; Jia, Ye1; Wu, Xiwei2; Schones, Dustin E.1; Natarajan, Rama1 | |
2019-08-15 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Angiotensin II (AngII) promotes hypertension and atherosclerosis by activating growth-promoting and pro-inflammatory gene expression in vascular smooth muscle cells (VSMCs). Enhancers and super-enhancers (SEs) play critical roles in driving disease-associated gene expression. However, enhancers/SEs mediating VSMC dysfunction remain uncharacterized. Here, we show that AngII alters vascular enhancer and SE repertoires in cultured VSMCs in vitro, ex vivo, and in AngII-infused mice aortas in vivo. AngII-induced enhancers/SEs are enriched in binding sites for signal-dependent transcription factors and dependent on key signaling kinases. Moreover, CRISPR-Cas9-mediated deletion of candidate enhancers/SEs, targeting SEs with the bromodomain and extra-terminal domain inhibitor JQ1, or knockdown of overlapping long noncoding RNAs (lncRNAs) blocks AngII-induced genes associated with growth-factor signaling and atherosclerosis. Furthermore, JQ1 ameliorates AngII-induced hypertension, medial hypertrophy and inflammation in vivo in mice. These results demonstrate AngII-induced signals integrate enhancers/SEs and lncRNAs to increase expression of genes involved in VSMC dysfunction, and could uncover novel therapies. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000414915900029 |
WOS关键词 | NF-KAPPA-B ; ETS-1 TRANSCRIPTION FACTOR ; GENE-EXPRESSION ; HUMAN GENOME ; HISTONE MODIFICATIONS ; SELECTIVE-INHIBITION ; BET BROMODOMAINS ; NONCODING RNAS ; DNA ELEMENTS ; INFLAMMATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204499 |
专题 | 资源环境科学 |
作者单位 | 1.City Hope Natl Med Ctr, Beckman Res Inst, Diabet Metab Res Inst, Dept Diabet Complicat & Metab, Duarte, CA 91010 USA; 2.City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol & Cellular Biol, Duarte, CA 91010 USA |
推荐引用方式 GB/T 7714 | Das, Sadhan,Senapati, Parijat,Chen, Zhuo,et al. Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Das, Sadhan.,Senapati, Parijat.,Chen, Zhuo.,Reddy, Marpadga A..,Ganguly, Rituparna.,...&Natarajan, Rama.(2019).Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells.NATURE COMMUNICATIONS,8. |
MLA | Das, Sadhan,et al."Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells".NATURE COMMUNICATIONS 8(2019). |
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