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Investigation of novel LPS-induced differentially expressed long non-coding RNAs in endothelial cells.
Mol Cell Biochem 2016; 421(1-2):157-68MC

Abstract

The molecular mechanisms responsible for sepsis-induced endothelial dysfunction leading to an elevated risk of cardiovascular diseases remain undefined. Endotoxic or septic shock is a potentially lethal complication of systemic infection by Gram-negative bacteria. Lipopolysaccharide (LPS) is a critical glycolipid component of the outer wall of Gram-negative bacteria, and many of the sepsis-associated cellular signals by Gram-negative bacteria are attributed to LPS. Given that LPS has an established role in the pathophysiology of sepsis and long non-coding RNAs (lncRNAs) have been reported to critically regulate vascular homeostasis, a systematic transcriptional survey was conducted to evaluate the impact of LPS stimulation on human endothelial lncRNAs and protein-coding transcripts (mRNAs). LncRNAs and mRNAs from LPS-treated (100 ng/mL; 24 h) human umbilical vein endothelial cells (HUVECs) were profiled with the Arraystar Human lncRNA Expression Microarray V3.0. Of the 30,584 lncRNAs screened, 871 were significantly upregulated and 1068 significantly downregulated (p < 0.05) in response to LPS. In the same HUVEC samples, 733 of the 26,106 mRNAs screened were upregulated and 536 were downregulated. Among the differentially expressed lncRNAs, AL132709.5 was the most upregulated (~70 fold) and CTC-459I6.1 the most downregulated (~28 fold). Bioinformatics analyses indicated that the differentially expressed upregulated mRNAs are primarily enriched in cytokine-cytokine receptor interaction, infectious diseases, TNF signaling pathway, FoxO signaling pathway, and pathways in cancer. This is the first lncRNA and mRNA transcriptome profile of LPS-mediated changes in human endothelial cells. These observations may reveal novel endothelial targets of LPS that may be involved in the vascular pathology of sepsis.

Authors+Show Affiliations

Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. singhk@smh.ca. Division of Vascular Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. singhk@smh.ca. Department of Surgery, University of Toronto, Toronto, ON, Canada. singhk@smh.ca. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. singhk@smh.ca.Division of Cardiology, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada. Institute of Medical Science, University of Toronto, Toronto, ON, Canada.Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.Division of Vascular Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. Department of Surgery, University of Toronto, Toronto, ON, Canada. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. King Saud University-Li Ka Shing Collaborative Research Program, Department of Surgery, King Saud University, Riyadh, Kingdom of Saudi Arabia.Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, 8th Floor, Bond Wing, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. vermasu@smh.ca. Department of Surgery, University of Toronto, Toronto, ON, Canada. vermasu@smh.ca. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. vermasu@smh.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27565812

Citation

Singh, Krishna K., et al. "Investigation of Novel LPS-induced Differentially Expressed Long Non-coding RNAs in Endothelial Cells." Molecular and Cellular Biochemistry, vol. 421, no. 1-2, 2016, pp. 157-68.
Singh KK, Matkar PN, Muhammad S, et al. Investigation of novel LPS-induced differentially expressed long non-coding RNAs in endothelial cells. Mol Cell Biochem. 2016;421(1-2):157-68.
Singh, K. K., Matkar, P. N., Muhammad, S., Quan, A., Gupta, V., Teoh, H., ... Verma, S. (2016). Investigation of novel LPS-induced differentially expressed long non-coding RNAs in endothelial cells. Molecular and Cellular Biochemistry, 421(1-2), pp. 157-68. doi:10.1007/s11010-016-2797-8.
Singh KK, et al. Investigation of Novel LPS-induced Differentially Expressed Long Non-coding RNAs in Endothelial Cells. Mol Cell Biochem. 2016;421(1-2):157-68. PubMed PMID: 27565812.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of novel LPS-induced differentially expressed long non-coding RNAs in endothelial cells. AU - Singh,Krishna K, AU - Matkar,Pratiek N, AU - Muhammad,Shoaib, AU - Quan,Adrian, AU - Gupta,Vijay, AU - Teoh,Hwee, AU - Al-Omran,Mohammed, AU - Verma,Subodh, Y1 - 2016/08/26/ PY - 2016/06/13/received PY - 2016/08/10/accepted PY - 2016/8/28/entrez PY - 2016/8/28/pubmed PY - 2017/2/7/medline KW - Endothelial cells KW - LPS KW - lncRNA SP - 157 EP - 68 JF - Molecular and cellular biochemistry JO - Mol. Cell. Biochem. VL - 421 IS - 1-2 N2 - The molecular mechanisms responsible for sepsis-induced endothelial dysfunction leading to an elevated risk of cardiovascular diseases remain undefined. Endotoxic or septic shock is a potentially lethal complication of systemic infection by Gram-negative bacteria. Lipopolysaccharide (LPS) is a critical glycolipid component of the outer wall of Gram-negative bacteria, and many of the sepsis-associated cellular signals by Gram-negative bacteria are attributed to LPS. Given that LPS has an established role in the pathophysiology of sepsis and long non-coding RNAs (lncRNAs) have been reported to critically regulate vascular homeostasis, a systematic transcriptional survey was conducted to evaluate the impact of LPS stimulation on human endothelial lncRNAs and protein-coding transcripts (mRNAs). LncRNAs and mRNAs from LPS-treated (100 ng/mL; 24 h) human umbilical vein endothelial cells (HUVECs) were profiled with the Arraystar Human lncRNA Expression Microarray V3.0. Of the 30,584 lncRNAs screened, 871 were significantly upregulated and 1068 significantly downregulated (p < 0.05) in response to LPS. In the same HUVEC samples, 733 of the 26,106 mRNAs screened were upregulated and 536 were downregulated. Among the differentially expressed lncRNAs, AL132709.5 was the most upregulated (~70 fold) and CTC-459I6.1 the most downregulated (~28 fold). Bioinformatics analyses indicated that the differentially expressed upregulated mRNAs are primarily enriched in cytokine-cytokine receptor interaction, infectious diseases, TNF signaling pathway, FoxO signaling pathway, and pathways in cancer. This is the first lncRNA and mRNA transcriptome profile of LPS-mediated changes in human endothelial cells. These observations may reveal novel endothelial targets of LPS that may be involved in the vascular pathology of sepsis. SN - 1573-4919 UR - https://www.unboundmedicine.com/medline/citation/27565812/Investigation_of_novel_LPS_induced_differentially_expressed_long_non_coding_RNAs_in_endothelial_cells_ L2 - https://doi.org/10.1007/s11010-016-2797-8 DB - PRIME DP - Unbound Medicine ER -