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首页> 外文期刊>Cell and Tissue Research >MicroRNA-27a/b mediates endothelin-1-induced PPAR gamma reduction and proliferation of pulmonary artery smooth muscle cells
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MicroRNA-27a/b mediates endothelin-1-induced PPAR gamma reduction and proliferation of pulmonary artery smooth muscle cells

机译:MicroRNA-27A / B介导内皮素-1-诱导的PPARγ还原和肺动脉平滑肌细胞的增殖

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摘要

The down-regulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) expression has been found to correlate with the proliferation of pulmonary artery smooth muscle cells (PASMC), pulmonary vascular remodeling and pulmonary hypertension, while the molecular mechanisms underlying PPAR gamma reduction in PASMC remain largely unclear. The aim of the current study is to address this issue. Endothelin-1 (ET-1) dose- and time-dependently resulted in PPAR gamma reduction and proliferation of primary cultured rat PASMC, which was accompanied by the activation of nuclear factor-kappaB (NF-kappa B) and subsequent induction of microRNA-27a/b (miR-27a/b) expression. Chromatin immunoprecipitation assay revealed that NF-kappa B directly bound to the promoter regions of miR-27a/b. Luciferase reporter assay identified that miR-27a/b directly regulates the expression of PPAR gamma in PASMC. Further study indicated that the presence of either NF-kappa B inhibitor pyrrolidinedithiocarbamate or prior silencing miR-27a/b with anti-miRNA oligonucleotides suppressed ET-1-induced PPAR gamma reduction and proliferation of PASMC, while overexpression of miR-27a/b reduced PPAR gamma expression and enhanced PASMC proliferation. Taken together, our study demonstrates that ET-1 stimulates miR-27a/b expression by activation of the NF-kappa B pathway, which in turn results in PPAR gamma reduction and contributes to ET-1-induced PASMC proliferation.
机译:已经发现过氧化物体增殖物激活的受体γ(PPARγ)表达的下调与肺动脉平滑肌细胞(PASMC),肺血管重塑和肺动脉高压的增殖相关,而PPARγ降低的分子机制PASMC仍然很大程度上不清楚。目前研究的目的是解决这个问题。内皮素-1(ET-1)剂量和时间依赖性导致初级培养大鼠PASMC的PPARγ降低和增殖,其伴随着核因子-κB(NF-Kappa B)的激活和随后的MicroRNA诱导 - 27a / b(miR-27a / b)表达。染色质免疫沉淀测定显示,NF-κB直接与miR-27a / b的启动子区域结合。荧光素酶报告结果确定MiR-27A / B直接调节PASMC中PPARγ的表达。进一步的研究表明,NF-Kappa B抑制剂吡咯烷酰胺的存在或具有抗miRNA寡核苷酸的先前沉默miR-27a / b抑制了抑制的ET-1诱导的PASMC的PPARγ还原和增殖,而MiR-27a / b的过度表达减少了PPARγ表达和增强的脂肪增殖。我们的研究表明,ET-1通过激活NF-Kappa B途径刺激MiR-27A / B表达,这反过来导致PPARγ降低并有助于ET-1诱导的脂肪增殖。

著录项

  • 来源
    《Cell and Tissue Research》 |2017年第3期|共13页
  • 作者单位

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

    Johns Hopkins Univ Div Allergy &

    Clin Immunol Dept Med Sch Med Baltimore MD 21224 USA;

    Xi An Jiao Tong Univ Sch Basic Med Sci Dept Pharmacol Hlth Sci Ctr Xian 710061 Shaanxi;

    Xi An Jiao Tong Univ Affiliated Hosp 1 Dept Resp &

    Crit Care Med Coll Med 277 Yanta West Rd;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Endothelin-1; Nuclear factor-kappaB; miR-27a/b; Peroxisome proliferator-activated receptor gamma; Pulmonary artery smooth muscle cells; Pulmonary hypertension;

    机译:内皮素-1;核因子 - κB;miR-27a / b;过氧化物组血增殖物激活的受体γ;肺动脉平滑肌细胞;肺动脉高压;

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