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

Int J Vasc Med

Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada M5B 1W8; Department of Surgery, University of Toronto, Toronto, ON, Canada M5T 1P5; Institute of Medical Science, University of Toronto, Toronto, ON, Canada M5S 1A8; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada M5S 1A8.

Published: May 2016

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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842052PMC
http://dx.doi.org/10.1155/2016/2459687DOI Listing

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