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转录组测序揭示了与间充质干细胞在主动脉夹层患者中作用相关的候选基因。

Transcriptome sequencing revealed candidate genes relevant to mesenchymal stem cells' role in aortic dissection patients.

机构信息

Department of Vascular Surgery, Changzheng Hospital, Shanghai 200003, P.R. China.

出版信息

Mol Med Rep. 2018 Jan;17(1):273-283. doi: 10.3892/mmr.2017.7851. Epub 2017 Oct 20.

Abstract

Aortic dissection (AD) results from the imbalance between synthesis and degradation of extracellular matrices in aortic wall, which is characterized by chronic inflammation. Mesenchymal stem cells (MSCs) are known for anti‑inflammatory and repairing effects and have therefore been studied for treatment for numerous diseases, including AD. However, it is unclear which genes or signaling pathways contribute to MSCs' role in AD. In the present study, RNA sequencing (RNA‑seq) was conducted between MSCs from patients with AS (AD‑MSCs) and those from age‑matched healthy donors (HD‑MSCs). RNA‑seq revealed 201 differentially expressed genes (DEGs) under the filter of fold change>2 and P‑value <0.05, in which 93 genes were upregulated and 108 downregulated. We selectively verified 9 out of 201 DEGs via reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) with an enlarged sample size. The trends of RT‑qPCR results were consistent with RNA‑seq data. Unsupervised hierarchical clustering of the 9‑gene expression profiles enables the division of clinical samples into AD and HD groups. Kyoto Encyclopedia of Genes and Genomes analysis displayed a significant change in adhesion‑related signaling pathways in AD‑MSCs compared with HD‑MSCs, whereas gene ontology analysis demonstrated DEGs were enriched in functions associated with development and morphogenesis, from a functional perspective. The present results indicate that gene expression profiles of AD‑MSCs were significantly changed compared with HD‑MSCs. These changes are probably associated with MSCs' adhesion capacity and development. These results may provide important insights into the role of MSCs in AD pathogenesis.

摘要

主动脉夹层(AD)是由于主动脉壁中外基质的合成和降解失衡引起的,其特征为慢性炎症。间充质干细胞(MSCs)具有抗炎和修复作用,因此已被研究用于治疗多种疾病,包括 AD。然而,尚不清楚哪些基因或信号通路有助于 MSCs 在 AD 中的作用。在本研究中,对来自动脉粥样硬化(AD)患者的 MSCs(AD-MSCs)和来自年龄匹配的健康供体的 MSCs(HD-MSCs)之间进行了 RNA 测序(RNA-seq)。RNA-seq 显示,在倍数变化>2 和 P 值<0.05 的过滤条件下,有 201 个差异表达基因(DEGs),其中 93 个基因上调,108 个基因下调。我们通过逆转录-定量聚合酶链反应(RT-qPCR)选择性地验证了 201 个 DEGs 中的 9 个,扩大了样本量。RT-qPCR 结果的趋势与 RNA-seq 数据一致。9 个基因表达谱的无监督层次聚类使临床样本能够分为 AD 和 HD 组。京都基因与基因组百科全书分析显示,AD-MSCs 中与黏附相关的信号通路发生了显著变化,而与黏附相关的信号通路与 HD-MSCs 相比,AD-MSCs 中与黏附相关的信号通路发生了显著变化。GO 分析显示,DEGs 富集在与发育和形态发生相关的功能中,从功能角度看。这些结果表明,AD-MSCs 的基因表达谱与 HD-MSCs 相比发生了显著变化。这些变化可能与 MSCs 的黏附能力和发育有关。这些结果可能为 MSCs 在 AD 发病机制中的作用提供重要见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab14/5780137/8e9805ad0c78/MMR-17-01-0273-g00.jpg

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