Department of Genetics and Molecular Biology, School of Medicine, Xi'an Jiaotong University, 76 Yanta West Road, Xi'an, 710061, Shaanxi, China.
NIHR Translational Research Facility in Respiratory Medicine Group, School of Translational Medicine, Stopford Building, University of Manchester, Manchester, M13 9PT, UK.
J Physiol Sci. 2013 Jan;63(1):31-38. doi: 10.1007/s12576-012-0230-y. Epub 2012 Sep 25.
Angiotensin II (Ang II) plays a pivotal role in cardiac fibrosis, and microRNAs (miRNAs) have been shown to participate in diverse pathological processes. Our aim is to identify the Ang II-induced miRNAs in cardiac fibroblasts (CFs). The miRNA array was used to analyze the miRNA expression profile in CFs treated by Ang II and control cells. Stem-loop real-time PCR was performed to re-measure the levels of the differentially expressed miRNAs. Analysis of miRNA arrays showed that 33 miRNAs were differentially expressed (13 up- and 20 downregulated) in response to Ang II (100 nM) for 24 h as compared to control cells. Quantitative PCR revealed that Ang II upregulated the levels of miR-132, -125b-3p and miR-146b but downregulated the levels of miR-300-5p, -204* and miR-181b in CFs. The trend of miRNA change is consistent with microarray and qRT-PCR. Bioinformatic analysis revealed that MMP9 as the target of miR-132, MMP16 as the target of miR-146b and TIMP3 as the target of miR-181b have been listed in the miR database with experimentally validated targets, indicating the potential role of those miRNAs in cardiac fibrosis. Our results demonstrated that we did identify a subset of miRNAs that was differentially expressed in Ang II-treated CFs, which provide a starting point to explore their potential roles in cardiac fibrosis and hypertension.
血管紧张素 II(Ang II)在心脏纤维化中起着关键作用,已有研究表明 microRNAs(miRNAs)参与了多种病理过程。我们的目的是鉴定 Ang II 诱导的心肌成纤维细胞(CFs)中的 miRNAs。采用 miRNA 芯片分析 Ang II 处理和对照细胞中 CFs 的 miRNA 表达谱。采用茎环实时 PCR 重新测量差异表达 miRNA 的水平。miRNA 芯片分析显示,与对照细胞相比,Ang II(100 nM)处理 24 h 后,有 33 个 miRNA 表达水平发生差异(13 个上调,20 个下调)。定量 PCR 显示,Ang II 上调了 miR-132、-125b-3p 和 miR-146b 的水平,但下调了 miR-300-5p、-204*和 miR-181b 的水平。miRNA 变化的趋势与微阵列和 qRT-PCR 一致。生物信息学分析显示,MMP9 是 miR-132 的靶标,MMP16 是 miR-146b 的靶标,TIMP3 是 miR-181b 的靶标,这些靶标已在 miR 数据库中列出,并具有实验验证的靶标,表明这些 miRNA 在心脏纤维化中的潜在作用。我们的结果表明,我们确实鉴定了一组在 Ang II 处理的 CFs 中差异表达的 miRNAs,这为探索它们在心脏纤维化和高血压中的潜在作用提供了起点。