Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells

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...

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Main Authors: Krishna K. Singh, Pratiek N. Matkar, Adrian Quan, Laura-Eve Mantella, Hwee Teoh, Mohammed Al-Omran, Subodh Verma
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:International Journal of Vascular Medicine
Online Access:http://dx.doi.org/10.1155/2016/2459687
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author Krishna K. Singh
Pratiek N. Matkar
Adrian Quan
Laura-Eve Mantella
Hwee Teoh
Mohammed Al-Omran
Subodh Verma
author_facet Krishna K. Singh
Pratiek N. Matkar
Adrian Quan
Laura-Eve Mantella
Hwee Teoh
Mohammed Al-Omran
Subodh Verma
author_sort Krishna K. Singh
collection DOAJ
description 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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spelling doaj-art-7396a5f1592b451f8a6b7ed439eb61bf2025-02-03T01:26:51ZengWileyInternational Journal of Vascular Medicine2090-28242090-28322016-01-01201610.1155/2016/24596872459687Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial CellsKrishna K. Singh0Pratiek N. Matkar1Adrian Quan2Laura-Eve Mantella3Hwee Teoh4Mohammed Al-Omran5Subodh Verma6Division of Vascular Surgery, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, M5B 1W8, CanadaInstitute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, CanadaDivision of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, M5B 1W8, CanadaDivision of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, M5B 1W8, CanadaDivision of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, M5B 1W8, CanadaDivision of Vascular Surgery, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, M5B 1W8, CanadaDivision of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, M5B 1W8, CanadaObjective. 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.http://dx.doi.org/10.1155/2016/2459687
spellingShingle Krishna K. Singh
Pratiek N. Matkar
Adrian Quan
Laura-Eve Mantella
Hwee Teoh
Mohammed Al-Omran
Subodh Verma
Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells
International Journal of Vascular Medicine
title Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells
title_full Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells
title_fullStr Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells
title_full_unstemmed Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells
title_short Investigation of TGFβ1-Induced Long Noncoding RNAs in Endothelial Cells
title_sort investigation of tgfβ1 induced long noncoding rnas in endothelial cells
url http://dx.doi.org/10.1155/2016/2459687
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