Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells.

IF 2.5 Q2 PERIPHERAL VASCULAR DISEASE
International Journal of Vascular Medicine Pub Date : 2016-01-01 Epub Date: 2016-04-10 DOI:10.1155/2016/2459687
Krishna K Singh, Pratiek N Matkar, Adrian Quan, Laura-Eve Mantella, Hwee Teoh, Mohammed Al-Omran, Subodh Verma
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引用次数: 15

Abstract

Objective. To evaluate the relationship between TGFβ signaling and endothelial lncRNA expression. Methods. Human umbilical vein endothelial cell (HUVECs) lncRNAs and mRNAs were profiled with the Arraystar Human lncRNA Expression Microarray V3.0 after 24 hours of exposure to TGFβ1 (10 ng/mL). Results. Of the 30,584 lncRNAs screened, 2,051 were significantly upregulated and 2,393 were appreciably downregulated (P < 0.05) in response to TGFβ. In the same HUVEC samples, 2,148 of the 26,106 mRNAs screened were upregulated and 1,290 were downregulated. Of these 2,051 differentially expressed upregulated lncRNAs, MALAT1, which is known to be induced by TGFβ in endothelial cells, was the most (~220-fold) upregulated lncRNA. Bioinformatics analyses indicated that the differentially expressed upregulated mRNAs are primarily enriched in hippo signaling, Wnt signaling, focal adhesion, neuroactive ligand-receptor interaction, and pathways in cancer. The most downregulated are notably involved in olfactory transduction, PI3-Akt signaling, Ras signaling, neuroactive ligand-receptor interaction, and apoptosis. Conclusions. This is the first lncRNA and mRNA transcriptome profile of TGFβ-mediated changes in human endothelial cells. These observations may reveal potential new targets of TGFβ in endothelial cells and novel therapeutic avenues for cardiovascular disease-associated endothelial dysfunction.

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tgf - β1诱导内皮细胞长链非编码rna的研究。
目标。目的:探讨tgf - β信号通路与内皮细胞lncRNA表达的关系。方法。暴露于tgf - β1 (10 ng/mL) 24小时后,使用Arraystar Human lncRNA Expression Microarray V3.0分析人脐静脉内皮细胞(HUVECs)的lncRNA和mrna。结果。在筛选的30584个lncrna中,2051个响应tgf - β显著上调,2393个明显下调(P < 0.05)。在相同的HUVEC样本中,筛选的26106个mrna中有2148个表达上调,1290个表达下调。在这2051个差异表达的上调lncRNA中,已知由内皮细胞TGFβ诱导的MALAT1是上调最多(约220倍)的lncRNA。生物信息学分析表明,差异表达的上调mrna主要富集于hippo信号、Wnt信号、局灶黏附、神经活性配体-受体相互作用和癌症通路。下调幅度最大的是嗅觉转导、PI3-Akt信号转导、Ras信号转导、神经活性配体受体相互作用和细胞凋亡。结论。这是人类内皮细胞中tgf β介导变化的第一个lncRNA和mRNA转录组谱。这些观察结果可能揭示内皮细胞中TGFβ的潜在新靶点和心血管疾病相关内皮功能障碍的新治疗途径。
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来源期刊
International Journal of Vascular Medicine
International Journal of Vascular Medicine PERIPHERAL VASCULAR DISEASE-
CiteScore
3.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
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