Long Non-Coding RNA MEG3 Downregulation Triggers Human Pulmonary Artery Smooth Muscle Cell Proliferation and Migration via the p53 Signaling Pathway
Long Non-Coding RNA MEG3 Downregulation Triggers Human Pulmonary Artery Smooth Muscle Cell Proliferation and Migration via the p53 Signaling Pathway
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DOI：
10.1159/000480218
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Liu, Yun
中科院分区：
文献类型：
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作者：
Sun, Zengxian;Nie, Xiaowei;Liu, Yun
背景/目的：越来越多的证据表明，长链非编码rna （IncRNAs）在多种生物过程中发挥着重要作用，其中许多可能在血管重构中发挥功能作用。然而，它们在肺动脉高压（PAH）中的功能在很大程度上仍然未知。肺血管重构是PAH的重要病理特征，导致血管阻力增加，顺应性降低。肺动脉平滑肌细胞（PASMCs）功能障碍与血管重构有关。长链非编码rna是PASMCs功能的潜在调控因子。本文中，我们确定了母体长链非编码RNA表达基因3 （MEG3）是否参与了pah相关的血管重构。方法：采用苏木精和伊红（H&E）染色法检测健康志愿者和PAH患者肺远端肺动脉（PAs）的动脉壁厚度。采用qPCR分析MEG3的表达水平。通过细胞计数Kit-8法、BrdU结合法、流式细胞术、划伤法、免疫荧光法和western blotting对人PASMCs进行检测，评估MEG3对人PASMCs的影响。结果：我们发现MEG3在PAH患者的肺和PAs中表达显著下调。MEG3敲低影响PASMCs体外增殖和迁移。此外，抑制MEG3可调节细胞周期进程，使更多的平滑肌细胞从G(0)/G(1)，期向G(2)/M+S期过渡，该过程可刺激PCNA、Cyclin A和Cyclin e的表达。此外，我们发现p53通路参与了MEG3诱导的平滑肌细胞增殖。结论：本研究确定MEG3是PAH的关键调节因子，并展示了基因治疗和药物开发治疗PAH的潜力。(C) 2017作者：s . Karger AG，巴塞尔出版
Background/Aims: Increasing evidence has demonstrated a significant role of long non coding RNAs (IncRNAs) in diverse biological processes, and many of which are likely to have functional roles in vascular remodeling. However, their functions in pulmonary arterial hypertension (PAH) remain largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Pulmonary artery smooth muscle cells (PASMCs) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of PASMCs function. Herein, we determined whether long noncoding RNA maternally expressed gene 3 (MEG3) was involved in PAH-related vascular remodeling. Methods: The arterial wall thickness was examined by hematoxylin and eosin (H&E) staining in distal pulmonary arteries (PAs) isolated from lungs of healthy volunteers and PAH patients. The expression level of MEG3 was analyzed by qPCR. The effects of MEG3 on human PASMCs were assessed by cell counting Kit-8 assay, BrdU incorporation assay, flow cytometry, scratch-wound assay, immunofluorescence, and western blotting in human PASMCs. Results:We revealed that the expression of MEG3 was significantly downregulated in lung and PAs of patients with PAH. MEG3 knockdown affected PASMCs proliferation and migration in vitro. Moreover, inhibition of MEG3 regulated the cell cycle progression and made more smooth muscle cells from the G(0)/G(1), phase to the G(2)/M+S phase and the process could stimulate the expression of PCNA, Cyclin A and Cyclin E. In addition, we found that the p53 pathway was involved in MEG3 induced smooth muscle cell proliferation. Conclusions: This study identified MEG3 as a critical regulator in PAH and demonstrated the potential of gene therapy and drug development for treating PAH. (C) 2017 The Author(s) Published by S. Karger AG, Basel