Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

YAP mediates TNF effect on pro-fibrotic genes expression

ABSTRACT: YAP/TAZ are transcription co-factors recently described responsive to pro-inflammatory cytokines and involved in inflammatory-related disorders. However, the role of tumor necrosis factor (TNF), a major pro-inflammatory cytokine, on YAP signaling is not well understood and controversial. Here, we observe in vitro, using wild type and YAP knockout HEK293 cells, that TNF triggers YAP nuclear translocation and transcriptional activity, thus being dependent on Rho family of GTPases. In response to TNF, YAP transcriptional activity orientates cell fate toward survival. Transcriptional analysis with Nanostring technology reveals that YAP modulates TNF-induced increase in fibro-inflammatory pathways such as NF-κB, inflammasomes, cytokines or chemokines signaling as well as pro-fibrotic pathways involving TGF-β and extracellular matrix remodeling. Therefore, in response to TNF, YAP acts as a sustainer of the inflammatory response and as a molecular link between inflammation and fibrotic processes. This work identifies that YAP is critical to drive several biological effects of TNF which are involved in cancer and inflammatory disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE194136 | GEO | 2022/03/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Modeling of Aberrant Epithelial Reprogramming in Idiopathic Pulmonary Fibrosis using Human Induced Pluripotent Stem Cell-derived Alveolar Organoids

Project description:Alveolar type 2 (AT2) organoids, derived from induced pluripotent stem cells, were stimulated with a fibrosis cocktail containing the pro-fibrotic and inflammatory cytokines TGF-β (5 ng/ml), TNF-α (10 ng/ml), PDGF-AB (10 ng/ml) and LPA (5 μM) or control cocktail containing diluents for 72 h.

2023-05-22 | E-MTAB-11676 | biostudies-arrayexpress

YAP mediates TNF effect on pro-fibrotic genes expression

Project description:YAP mediates TNF effect on pro-fibrotic genes expression

| PRJNA799310 | ENA

Inflammatory stress-mediated chromatin changes underlie dysfunction in endothelial cells. [ATAC-Seq]

Project description:Inflammatory stresses underlie endothelial dysfunction and contribute to the development of chronic cardiovascular disorders such as atherosclerosis and vascular fibrosis. The initial transcriptional response of endothelial cells to pro-inflammatory cytokines such as TNF-alpha is well established. However, very few studies uncover the effects of inflammatory stresses on chromatin architecture. We used integrative analysis of ATAC-seq and RNA-seq data to investigate chromatin alterations in human endothelial cells in response to TNF-alpha and febrile-range heat stress exposure. Multi-omics data analysis suggests a correlation between the transcription of stress-related genes and endothelial dysfunction drivers with chromatin regions exhibiting differential accessibility.

2024-05-25 | GSE267931 | GEO

Inflammatory stress-mediated chromatin changes underlie dysfunction in endothelial cells. [RNA-Seq]

2024-05-25 | GSE267930 | GEO

TRIM21 innate immune detection of GBP1-positive Toxoplasma gondii is essential for host survival

Project description:Interferon gamma (IFN) is the major pro-inflammatory cytokine conferring resistance to the intracellular vacuolar pathogen Toxoplasma gondii. Autophagy along with immunity-related GTPases (IRGs), guanylate binding proteins (GBPs) and the E3 ubiquitin ligase TNF receptor-associated factor 6 (TRAF6) mediate clearance of Toxoplasma in IFN-stimulated cells. With the exception of inflammasomes, no host innate immune mediators impacting host survival have been identified at disrupted parasitophorous vacuoles. We show that IFN drives recruitment of the E3 ubiquitin ligase TRIM21 to GBP1-positive avirulent Toxoplasma vacuoles. This led to Lys63-linked ubiquitination of the vacuole and secretion of pro-inflammatory cytokines. GBPs were ubiquitinated during infection and TRIM21 controlled their expression levels and the efficient recruitment of GBP1 to the vacuole. TRIM21 deficiency led to an enhanced early replication of Toxoplasma without interfering with vacuolar disruption. TRIM21-/- mice were highly susceptible to Toxoplasma infection, exhibiting decreased levels of pro-inflammatory cytokines and higher parasite burden in the brain. This study identifies TRIM21 as a previously unknown modulator of Toxoplasma gondii resistance thereby extending host innate immune recognition of eukaryotic pathogens to include E3 ubiquitin ligases.

2018-03-12 | PXD003217 | Pride

Lipopolysaccharide induced inflammatory response in mouse intestinal epithelial cells

Project description:Lipopolysaccharides (LPS) can lead to a lethal endotoxemia, which is a systemic inflammatory response syndrome (SIRS) characterized by a systemic release of cytokines, such as TNF. Endotoxemia is studied intensely, as a model system of gram-negative infections. LPS- as well as TNF-induced SIRS involve a strong induction of pro-inflammatory genes. In this study we investigate the response of the intestinal epithelium cells (IECs) ot LPS and may produce pro-inflammatory cytokines or suffer cell death.

2020-03-20 | GSE139903 | GEO

Influence of Interferon-beta on expression profile of memory T-cells

Project description:Inflammasomes are multi-protein complexes that control the production of pro-inflammatory cytokines such as IL-1beta. Inflammasomes play an important role in the control of immunity to tumors and infections, and also in autoimmune diseases, but the mechanisms controlling the activation of human inflammasomes are largely unknown. We found that human activated CD4+CD45RO+ memory T-cells specifically suppress P2X7R-mediated NLRP3 inflammasome activation, without affecting P2X7R-independent NLRP3 or NLRP1 inflammasome activation. The concomitant increase in pro-IL-1β production induced by activated memory T-cells concealed this effect. Priming with IFNβ decreased pro-IL-1β production in addition to NLRP3 inflammasome inhibition and thus unmasked the inhibitory effect on NLRP3 inflammasome activation. IFNβ did not suppress NLRP3 inflammasome activation by acting directly on monocytes. The inhibition of pro-IL-1β production and suppression of NLRP3 inflammasome activation by IFNβ-primed human CD4+CD45RO+ memory T-cells is partly mediated by soluble FasL and is associated with down-regulated P2X7R mRNA expression and reduced response to ATP in monocytes. CD4+CD45RO+ memory T-cells from multiple sclerosis (MS) patients showed a reduced ability to suppress NLRP3 inflammasome activation, however their suppressive ability was recovered following in vivo treatment with IFNβ. Thus, our data demonstrate that human P2X7R-mediated NLRP3 inflammasome activation is regulated by activated CD4+CD45RO+ memory T cells, and provide new information on the mechanisms mediating the therapeutic effects of IFNβ in MS. Memory T-cells were cultured in the presence of monocytes with and without Interferon-beta, resorted and expression profile was determined

2012-12-01 | E-GEOD-35601 | biostudies-arrayexpress

Mind Bomb 2 limits inflammatory dermatitis in Sharpin mutant mice independently of cell death

Project description:Skin inflammation is a complex process implicated in various dermatological disorders. The chronic proliferative dermatitis (cpd) phenotype driven by the cpd mutation (cpdm) in the Sharpin gene is characterized by dermal inflammation and epidermal abnormalities. TNF and caspase-8-driven cell death causes the pathogenesis of Sharpincpdm mice, however, the role of MIB2, a pro-survival E3 ubiquitin ligase involved in TNF-signalling, in skin inflammation remains unknown. Here we demonstrate that MIB2 antagonises inflammatory dermatitis in the context of the cpd mutation. Surprisingly, the role of MIB2 in limiting skin inflammation is independent of its known pro-survival function and E3 ligase activity. Instead, MIB2 enhances the production of wound healing molecules, G-CSF and Eotaxin, within the skin. This discovery advances our comprehension of inflammatory cytokines and chemokines involved in cpdm pathogenesis, and highlights the significance of MIB2 in inflammatory skin disease that is independent of its ability to regulate TNF-induced cell death.

2024-01-25 | PXD045850 | Pride

Anti-Interleukin-10 unleashes transcriptional response to leishmanial antigen in whole blood of visceral leishmaniasis patients

Project description:Visceral leishmaniasis (VL; Leishmania donovani) cases produce interferon- (IFN) and tumour necrosis factor (TNF) in response to soluble leishmanial antigen (SLA) in whole blood assays. These pro-inflammatory cytokines are crucial for activation of macrophages to kill L. donovani parasites. Detailed immunological studies comparing active with cured patients suggest that a balance exists between the pro-inflammatory cytokines TNF and IFN, and anti-inflammatory interleukin-10 (IL10). Our interest was to obtain a global understanding of the response to SLA in whole blood from active VL cases, and to determine what effect neutralising anti-IL10 would have on this response. Transcriptional profiles following SLA stimulation of whole blood from VL patients showed very few differentially expressed genes (DEGs), the majority belonging to a single network with TNF at the hub. In contrast, when anti-IL10 was added with SLA, hundreds of DEGs were observed, 65% belonging to a single network with TNF, IFNG, NFKBIA, IL6 and IL1B as hub genes in concert with a remarkable chemokine/cytokine storm. Our data demonstrate the singular impact of IL10 as a potent immune modulator in VL.

2021-03-31 | GSE146908 | GEO

Pla2g6-dependent cytokine signaling in MIN6 cells

Project description:Analysis of MIN6 murine beta cell line transfected with Pla2g6 RNAi and treated with pro-inflammatory cytokines TNF-alpha, IL-1beta and IFN-gamma.

2024-02-08 | PXD017863 | Pride

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