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.
引用
收藏
页数:12
相关论文
共 70 条
  • [61] HELLP babies link a novel lincRNA to the trophoblast cell cycle
    van Dijk, Marie
    Thulluru, Hari K.
    Mulders, Joyce
    Michel, Omar J.
    Poutsma, Ankie
    Windhorst, Sandra
    Kleiverda, Gunilla
    Sie, Daoud
    Lachmeijer, Augusta M. A.
    Oudejans, Cees B. M.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (11) : 4003 - 4011
  • [62] Long Noncoding RNAs in Patients With Acute Myocardial Infarction
    Vausort, Melanie
    Wagner, Daniel R.
    Devaux, Yvan
    [J]. CIRCULATION RESEARCH, 2014, 115 (07) : 668 - U180
  • [63] Targeting long non-coding RNA to therapeutically upregulate gene expression
    Wahlestedt, Claes
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2013, 12 (06) : 433 - 446
  • [64] Long noncoding RNAs and human disease
    Wapinski, Orly
    Chang, Howard Y.
    [J]. TRENDS IN CELL BIOLOGY, 2011, 21 (06) : 354 - 361
  • [65] LincRNA-p21 Regulates Neointima Formation, Vascular Smooth Muscle Cell Proliferation, Apoptosis, and Atherosclerosis by Enhancing p53 Activity
    Wu, Gengze
    Cai, Jin
    Han, Yu
    Chen, Jinghai
    Huang, Zhan-Peng
    Chen, Caiyu
    Cai, Yue
    Huang, Hefei
    Yang, Yujia
    Liu, Yukai
    Xu, Zaicheng
    He, Duofen
    Zhang, Xiaoqun
    Hu, Xiaoyun
    Pinello, Luca
    Zhong, Dan
    He, Fengtian
    Yuan, Guo-Cheng
    Wang, Da-Zhi
    Zeng, Chunyu
    [J]. CIRCULATION, 2014, 130 (17) : 1452 - U64
  • [66] Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Improves Survival of Patients with Peritoneal Carcinomatosis from Gastric Cancer: Final Results of a Phase III Randomized Clinical Trial
    Yang, Xiao-Jun
    Huang, Chao-Qun
    Suo, Tao
    Mei, Lie-Jun
    Yang, Guo-Liang
    Cheng, Fu-Lin
    Zhou, Yun-Feng
    Xiong, Bin
    Yonemura, Yutaka
    Li, Yan
    [J]. ANNALS OF SURGICAL ONCOLOGY, 2011, 18 (06) : 1575 - 1581
  • [67] MALAT1 long non-coding RNA in cancer
    Yoshimoto, Rei
    Mayeda, Akila
    Yoshida, Minoru
    Nakagawa, Shinichi
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2016, 1859 (01): : 192 - 199
  • [68] Endothelial-to-mesenchymal transition contributes to cardiac fibrosis
    Zeisberg, Elisabeth M.
    Tarnavski, Oleg
    Zeisberg, Michael
    Dorfman, Adam L.
    McMullen, Julie R.
    Gustafsson, Erika
    Chandraker, Anil
    Yuan, Xueli
    Pu, William T.
    Roberts, Anita B.
    Neilson, Eric G.
    Sayegh, Mohamed H.
    Izumo, Seigo
    Kalluri, Raghu
    [J]. NATURE MEDICINE, 2007, 13 (08) : 952 - 961
  • [69] The lncRNA Malat1 Is Dispensable for Mouse Development but Its Transcription Plays a cis-Regulatory Role in the Adult
    Zhang, Bin
    Arun, Gayatri
    Mao, Yuntao S.
    Lazar, Zsolt
    Hung, Gene
    Bhattacharjee, Gourab
    Xiao, Xiaokun
    Booth, Carmen J.
    Wu, Jie
    Zhang, Chaolin
    Spector, David L.
    [J]. CELL REPORTS, 2012, 2 (01): : 111 - 123
  • [70] Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome
    Zhao, Jing
    Sun, Bryan K.
    Erwin, Jennifer A.
    Song, Ji-Joon
    Lee, Jeannie T.
    [J]. SCIENCE, 2008, 322 (5902) : 750 - 756