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学科主题: 基础医学
题名:
Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth
作者: Wang, Kuei-Chun1,2; Garmire, Lana Xia1,2; Young, Angela1,2; Nguyen, Phu1,2; Trinh, Andrew1,2; Subramaniam, Shankar1,2; Wang, Nanping3; Shyy, John Y. J.4; Li, Yi-Shuan1,2; Chien, Shu1,2
关键词: cell cycle ; shear ; bioinformatics ; gene regulation ; mechanotransduction
刊名: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
发表日期: 2010-02-16
DOI: 10.1073/pnas.0914825107
卷: 107, 期:7, 页:3234-3239
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: LAMINAR SHEAR-STRESS ; GENE-EXPRESSION ; TARGET PREDICTIONS ; ANGIOGENESIS ; IDENTIFICATION ; PROLIFERATION ; RECRUITMENT ; MECHANISM ; PROFILES ; GENOMICS
英文摘要:

MicroRNAs (miRs) can regulate many cellular functions, but their roles in regulating responses of vascular endothelial cells (ECs) to mechanical stimuli remain unexplored. We hypothesize that the physiological responses of ECs are regulated by not only mRNA and protein signaling networks, but also expression of the corresponding miRs. EC growth arrest induced by pulsatile shear (PS) flow is an important feature for flow regulation of ECs. miR profiling showed that 21 miRs are differentially expressed (8 up- and 13 downregulated) in response to 24-h PS as compared to static condition (ST). The mRNA expression profile indicates EC growth arrest under 24-h PS. Analysis of differentially expressed miRs yielded 68 predicted mRNA targets that overlapped with results of microarray mRNA profiling. Functional analysis of miR profile indicates that the cell cycle network is highly regulated. The upregulation of miR-23b and miR-27b was found to correlate with the PS-induced EC growth arrest. Inhibition of miR-23b using antagomir-23b oligonucleotide (AM23b) reversed the PS-induced E2F1 reduction and retinoblastoma (Rb) hypophosphorylation and attenuated the PS-induced G1/G0 arrest. Antagomir AM27b regulated E2F1 expression, but did not affect Rb and growth arrest. Our findings indicate that PS suppresses EC proliferation through the regulation of miR-23b and provide insights into the role of miRs in mechanotransduction.

语种: 英语
所属项目编号: HL064382 ; HL085159 ; HL080518 ; HL087375 ; DK074868 ; HL89940 ; TMS-094-1A-004
项目资助者: National Institutes of Health ; Taiwan National Science Council
WOS记录号: WOS:000274599500094
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62362
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
2.Univ Calif San Diego, Inst Engn Med, La Jolla, CA 92093 USA
3.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
4.Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA

Recommended Citation:
Wang, Kuei-Chun,Garmire, Lana Xia,Young, Angela,et al. Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2010,107(7):3234-3239.
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