Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LncRNA ICR regulates endothelium inflammation through feedback activation of NF-κB signaling

ABSTRACT: The responsive and abundant lncRNAs to pro-inflammatory factors in human ECs were screened and validated by RNA sequencing and qPCR. ICAM1-related non-coding RNA (ICR) was identified as the most potential candidate. In vivo data confirmed ICR was upregulated in atherosclerotic plaque. Knock down and overexpression experiments showed that ICR plays an essential role for EC adhesion and migration as well as for the expression of its adjacent ICAM1 gene. Mechanistically, we unexpectedly found in quiescent ECs, ICR regulates mRNA stabilization of ICAM1 through a RNA duplex formation mechanism while in activated ECs, ICR modulated ICAM1 transcription via a NF-κB-dependent manner. RNA-seq and PCR analysis demonstrated a vast number of pro-inflammatory genes downstream of NF-κB were regulated by ICR. Further, CHIP assay showed p65 directly binds to ICR promoter and facilitate the transcription. Interestingly, we found p65 phosphorylation and degradation was in turn regulated by ICR, forming a feedback activation of NF-κB signaling. Finally, we screened siRNA of mouse ICR and delivered the shRNA adenovirus by intravenous injection in a high fat diet induced ApoE-/- atherosclerosis model, it was found that both aortic root stenosis and plaque area could be markedly inhibited by suppressing ICR.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184512 | GEO | 2022/06/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Genome wide analysis of HDL and cyclodextrin induced gene expression in LPS-stimulated bone marrow derived macrophages

Project description:While LPS as expected induced a strongly upregulatedion of pro-inflammatory genes and signaling pathways, HDL and cyclodextrin clearly enhanced LPS-induced signaling, especially of Interferon Regulatory Factor (IRF)1 and Nuclear Factor-κB (NF-κB)-p65 dependent genes

2016-11-17 | GSE70155 | GEO

Multi-species RELA ChIP-seq of mammalian aortic endothelial cells before and after TNFα stimulation

Project description:TNFα has an evolutionary conserved role in mediating inflammation via activation of the transcription factor NF-κB. The functions of individual NF-κB binding sites are not well understood. To identify conserved and functionally important NF-κB binding sites in mammals, we performed ChIP-seq to map the genome-wide binding of RELA and select histone modifications in primary vascular endothelial cells (ECs) isolated from the aortas of human (HAEC), mouse (MAEC) and cow (BAEC), before and after TNFα. The conserved RELA binding sites show strong epigenetic changes in response to TNFα and enrich near genes controlling vascular development and pro-inflammatory responses. Our method identifies novel modes of RELA-chromatin interactions that are conserved in mammals and shared between multiple cell-types. Particularly, genomic regions bound by RELA prior to stimulation are important responders during TNFα stimulation. We use CRISPR/Cas9 genome editing to validate the roles of the conserved RELA pre-bound sites near pro-inflammatory genes such as CCL2 and PLK2. Our evolutionary approach describes new aspects of mammalian NF-κB biology including its role within super-enhancers and relevance in inflammatory disorders.

2020-10-03 | E-MTAB-7889 | biostudies-arrayexpress

CD95/Fas suppresses NF-B activation through recruitment of KPC2 in a CD95L/FasL-independent mechanism

Project description:CD95 expression is preserved in triple-negative breast cancers (TNBCs) and CD95 loss in these cells triggers the induction of a pro-inflammatory program promoting the recruitment of cytotoxic NK cells impairing tumor growth. Herein, we identify a novel interaction partner of CD95, Kip1 ubiquitination-promoting complex protein 2 (KPC2) using an unbiased proteomic approach. Independently of CD95L, CD95/KPC2 interaction contributes to the partial degradation of p105 (NFκB1) and the subsequent generation of p50 homodimers, which transcriptionally represses NF-κB-driven gene expression. Mechanistically, KPC2 interacts with the C-terminal region of CD95 and serves as an adaptor to recruit RelA (p65) and KPC1, which acts as E3 ubiquitin-protein ligase promoting the degradation of p105 into p50. Loss of CD95 in TNBC cells releases KPC2, limiting the formation of the NF-κB inhibitory homodimer complex (p50/p50), promoting NF-κB activation and the production of pro-inflammatory cytokines, that could account for the immune landscape remodeling in TNBC cells

2021-12-06 | PXD027196 | Pride

The activation of IL-1 induced enhancers depends on TAK1 kinase activity and NF-KB p65 [ChIP-Seq]

Project description:The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-κB subunit p65 in relation to active enhancers and promoters of transcribed genes by ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin (IL)-1-induced H3K27ac and p65 binding. Inhibition of TAK1, IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-κB p50 and of AP-1 transcription factors to both, promoters and enhancers. This study provides a high resolution view of epigenetic changes occurring during the IL-1 response and allows the first genome-wide identification of a novel class of inducible p65 NF-κB-dependent enhancers in epithelial cells. ChIP-seq in KB cells with 5 different antibodies under different treatment conditions

2014-12-16 | E-GEOD-64223 | biostudies-arrayexpress

LncRNA ICR regulates endothelium inflammation through feedback activation of NF-κB signaling

Project description:LncRNA ICR regulates endothelium inflammation through feedback activation of NF-κB signaling

| PRJNA764870 | ENA

The role of MAGI1 (membrane-associated guanylate kinase with inverted domain structure-1) in regulating disturbed flow-induced changes of gene expression

Project description:To understand the function of MAGI1 in ECs, we isolated total RNAs from human umblical vein endothelial cells (HUVECs) transfected with control or Magi1 siRNA and transcriptionally profiled them. Ingenuity pathway Analysis (IPA) demonstrated activation of antiviral responses, including interferon signaling, without affecting NF-κB expression and inhibition of ER stress gene expression induced by the reduction of MAGI1 expression. Because activation of interferon signaling tends to increase NF-κB activation, the finding that depletion of MAGI1 promotes antiviral responses without increasing NF-κB activation is unique, suggesting that MAGI1 is an incomparable molecular switch for pro-viral and pro-inflammatory responses.

2019-05-09 | GSE95066 | GEO

ATAC-seq of primary mammalian aortic endothelial cells before and after TNFα stimulation

Project description:To identify conserved TNFα-induced changes in chromatin-accessibility in mammals, we performed ATAC-seq in primary vascular endothelial cells (ECs) isolated from the aortas of human (HAEC), mouse (MAEC) and cow (BAEC), before and after TNFα. We overlay our data with multi-species NF-κB binding data and identify multiple modes of NF-κB-chromatin interactions that are conserved during mammalian TNFα response. Our cross-species approach identifies conserved changes in chromatin-accessibility at NF-κB binding sites that are disease-relevant and essential during mammalian acute inflammation.

2020-06-01 | E-MTAB-7878 | biostudies-arrayexpress

Cyclin-dependent kinase 6 is a chromatin-bound cofactor for nuclear factor kappaB-dependent gene expression [Agilent]

Project description:Given the intimate link between inflammation and dysregulated cell proliferation in cancer we investigated cytokine-triggered gene expression in different cell cycle stages. High density microarray analysis revealed that G1 release primes and cooperates with the cytokine-driven gene response. This effect is transmitted through CDK6 which shares the ability to regulate expression of inflammatory genes with its functional homologue CDK4. CDK6 contributes to the regulation of inflammatory gene expression by physical and functional cooperation with the NF-κB subunit p65 in the nucleus. ChIPSeq experiments showed a tight co-recruitment of CDK6 and p65 to enhancers and promoters of many transcriptionally active NF-κB target genes. While CDK6 recruitment to distinct chromatin regions of inflammatory target genes had no effect on histone modifications, it was essential for proper loading of NF-κB p65 to its cognate binding sites and for the function of p65 coactivators such as TRIP6. Furthermore, cytokine-inducible nuclear translocation and chromatin association of CDK6 depends on the kinase activity of TAK1 and p38. These results have widespread biological implications, as aberrant CDK6 expression or activation that is frequently observed in human tumors cooperates with NF-κB to shape the cytokine- and chemokine-repertoire in chronic inflammation and cancer. Four sets of experiments were performed in total (Exp1-4). Within each of these sets biological duplicates (Rep1-2) were included and analyzed. HeLa control cells or cells with established shRNA-mediated knockdown of CDK4 or CDK6 were analyzed. Cells were subjected to cell cycle arrest or were released from the arrested state for 6h. Cells were treated for 30 minutes with Interleukin-1-alpha at the arrested state or after release or were left untreated.

2013-12-31 | E-GEOD-52465 | biostudies-arrayexpress

PKCα-LSD1-NF-κB Signaling Cascade Is Crucial for Epigenetic Control of the Inflammatory Response [RNA-Seq]

Project description:The inflammatory response mediated by NF-κB signaling is essential for host defense against pathogens. Although the components and regulatory mechanism of NF-κB signaling have been well-studied, molecular basis for the epigenetic regulation of the inflammatory response is poorly understood. Here, we identify a new signaling axis of PKCα- LSD1-NF-κB p65 which is critical for activation and amplification of the inflammatory response and triggering systemic inflammatory diseases. In response to excessive inflammatory stimuli, PKCα translocates to the nucleus and phosphorylates LSD1. Phosphorylation of LSD1 is required for its interaction with p65 and facilitates demethylation of p65 leading to enhanced protein stability. Genome-wide analysis reveals a critical role of LPS-induced LSD1 phosphorylation in the transcriptional activation of NF-κB target genes. Together, we demonstrate that PKCα-LSD1-NF-κB signaling cascade is crucial for epigenetic control of the inflammatory response.

2018-01-31 | GSE100216 | GEO

PKCα-LSD1-NF-κB Signaling Cascade Is Crucial for Epigenetic Control of the Inflammatory Response [ChIP-Seq]

2018-01-31 | GSE107989 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data