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Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth

机译:microRNA-23b在Rb磷酸化和内皮细胞生长的流量调节中的作用

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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) hypophosphoryla-tion 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.
机译:MicroRNA(miRs)可以调节许多细胞功能,但它们在调节血管内皮细胞(EC)对机械刺激的反应中的作用仍待探索。我们假设EC的生理反应不仅受mRNA和蛋白质信号网络的调节,还受相应miRs表达的调节。脉动剪切(PS)流动引起的EC生长停滞是EC流量调节的重要特征。 miR分析显示,与静态条件(ST)相比,响应24小时PS,差异表达了21个miR(上调了8个,下调了13个)。 mRNA表达谱表明在24小时PS下EC生长停滞。分析差异表达的miRs可产生68个预测的mRNA靶标,与微阵列mRNA谱分析的结果重叠。 miR谱的功能分析表明,细胞周期网络受到高度调控。发现miR-23b和miR-27b的上调与PS诱导的EC生长停滞有关。使用antagomir-23b寡核苷酸(AM23b)抑制miR-23b可以逆转PS诱导的E2F1减少和视网膜母细胞瘤(Rb)的低磷酸化,并减弱PS诱导的G1 / G0阻滞。 Antagomir AM27b调节E2F1表达,但不影响Rb和生长停滞。我们的发现表明PS通过miR-23b的调节抑制EC增殖,并提供对miR在机械转导中的作用的见解。

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    Department of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093;

    rnDepartment of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093;

    rnDepartment of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093;

    rnDepartment of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093;

    rnDepartment of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093;

    rnDepartment of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093;

    rnKey Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing 100191, China;

    rnDivision of Biomedical Sciences, University of California, Riverside, CA 92521;

    rnDepartment of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093;

    rnDepartment of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cell cycle; shear; bioinformatics; gene regulation; mechanotransduction;

    机译:细胞周期;剪生物信息学基因调控;机械转导;

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