气候变化领域集成服务门户(CCPortal): A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock

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DOI	10.1073/pnas.2016648118
	A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock
	Vollmers A.C.; Covarrubias S.; Kuang D.; Shulkin A.; Iwuagwu J.; Katzman S.; Song R.; Viswanathan K.; Vollmers C.; Wakeland E.; Carpenter S.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	Recent studies have identified thousands of long noncoding RNAs (lncRNAs) in mammalian genomes that regulate gene expression in different biological processes. Although lncRNAs have been identified in a variety of immune cells and implicated in immune response, the biological function and mechanism of the majority remain unexplored, especially in sepsis. Here, we identify a role for a lncRNA—gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC)—previously characterized for its role in cancer, now in the context of innate immunity, macrophages, and LPS-induced endotoxic shock. Transcriptome analysis of macrophages from humans and mice reveals that GAPLINC is a conserved lncRNA that is highly expressed following macrophage differentiation. Upon inflammatory activation, GAPLINC is rapidly down-regulated. Macrophages depleted of GAPLINC display enhanced expression of inflammatory genes at baseline, while overexpression of GAPLINC suppresses this response. Consistent with GAPLINC-depleted cells, Gaplinc knockout mice display enhanced basal levels of inflammatory genes and show resistance to LPS-induced endotoxic shock. Mechanistically, survival is linked to increased levels of nuclear NF-κB in Gaplinc knockout mice that drives basal expression of target genes typically only activated following inflammatory stimulation. We show that this activation of immune response genes prior to LPS challenge leads to decreased blood clot formation, which protects Gaplinc knockout mice from multiorgan failure and death. Together, our results identify a previously unknown function for GAPLINC as a negative regulator of inflammation and uncover a key role for this lncRNA in modulating endotoxic shock. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Long noncoding RNA \| inflammation \| GAPLINC \| innate immunity \| sepsis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180611
作者单位	Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, United States; Genomics Institute, University of California, Santa Cruz, CA 95064, United States; Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9093, United States; Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, United States
推荐引用方式 GB/T 7714	Vollmers A.C.,Covarrubias S.,Kuang D.,et al. A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock[J],2021,118(7).
APA	Vollmers A.C..,Covarrubias S..,Kuang D..,Shulkin A..,Iwuagwu J..,...&Carpenter S..(2021).A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Vollmers A.C.,et al."A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).