Investigation of TGF beta 1-Induced Long Noncoding RNAs in Endothelial Cells

被引:15
作者
Singh, Krishna K. [1 ,2 ,3 ,4 ]
Matkar, Pratiek N. [4 ,5 ]
Quan, Adrian [2 ]
Mantella, Laura-Eve [2 ,6 ]
Teoh, Hwee [2 ,7 ]
Al-Omran, Mohammed [1 ,3 ,4 ,8 ,9 ]
Verma, Subodh [2 ,3 ,4 ,6 ]
机构
[1] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Div Vasc Surg, 30 Bond St, Toronto, ON M5B 1W8, Canada
[2] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Div Cardiac Surg, 30 Bond St, Toronto, ON M5B 1W8, Canada
[3] Univ Toronto, Dept Surg, Toronto, ON M5T 1P5, Canada
[4] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada
[5] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Div Cardiol, 30 Bond St, Toronto, ON M5B 1W8, Canada
[6] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada
[7] St Michaels Hosp, Li Ka Shing Knowledge Inst, Div Endocrinol & Metab, 30 Bond St, Toronto, ON M5B 1W8, Canada
[8] King Saud Univ, Dept Surg, Riyadh 12372, Saudi Arabia
[9] King Saud Univ, Li Ka Shing Collaborat Res Program, Riyadh 12372, Saudi Arabia
基金
加拿大健康研究院;
关键词
D O I
10.1155/2016/2459687
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Objective. To evaluate the relationship between TGF beta 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 TGF beta 1 ( 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 TGF beta. 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 TGF beta in endothelial cells, was the most (similar to 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 TGF beta-mediated changes in human endothelial cells. These observations may reveal potential new targets of TGF beta in endothelial cells and novel therapeutic avenues for cardiovascular disease-associated endothelial dysfunction.
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页数:12
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