Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1041289 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26847900.fastq.gz | Fastqsanger.gz | |||
| SRR26847901.fastq.gz | Fastqsanger.gz | |||
| SRR26847902.fastq.gz | Fastqsanger.gz | |||
| SRR26847903.fastq.gz | Fastqsanger.gz | |||
| SRR26847904.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 64 |
Similar Datasets
Project description:A member of the nuclear receptors, retinoic acid-related orphan receptor a (RORa) is an important transcription factor for various biological processes including circadian rhythm, metabolic regulation, immune cell development and cancer. Here we found that RORa is important for intestinal homeostasis by negatively regulating the transcriptional activity of NF-kB, a major inflammatory regulator in intestinal epithelial cells. Intestinal Rora-deficient mice found were highly susceptible to DSS-induced injury. Transcriptome analysis showed that intestine-specific Rora deletion causes regulatory impairment of NF-kB signaling leading to excessive inflammatory responses. RORa specifically binds to the NF-kB target promoter and inhibits transcriptional activity for transcriptional repression of NF-kB activity via histone deacetylase 3 (HDAC3). Taken together, RORa plays a pivotal role in the homeostatic regulation of intestinal epithelial cells in inflammatory conditions. Therefore, therapeutic strategies designed to modulate RORa activity may be beneficial in the treatment of chronic inflammatory diseases such as Inflammatory bowel disease (IBD).
2019-09-30 | GSE121977 | GEO
Project description:The canonical NF-kB module induces nuclear translocation of RelA heterodimers from the latent cytoplasmic complexes. RelA directs inflammatory immune responses against microbial entities. However, aberrant RelA activity also triggers destructive inflammation, including those associated with inflammatory bowel disease (IBD). What provokes this pathological RelA activity remains unclear. As such, the noncanonical NF-kB pathway activates RelB heterodimers and mediates immune organogenesis. Because NF-kB-activating pathways are interlinked, we asked if noncanonical NF-kB signaling exacerbated intestinal inflammation. Our investigation revealed recurrent engagement of the noncanonical pathway in human IBD. In a mouse model of chemical colitis, the noncanonical NF-kB signaling gene Nfkb2 aggravated inflammation by amplifying the RelA activity induced in intestinal epithelial cells. Our mechanistic studies clarified that noncanonical signaling augmented the abundance of latent RelA complexes leading to hyperactive canonical NF-kB response in the colitogenic gut. In sum, latent dimer homeostasis appears to link noncanonical NF-kB signaling to RelA-driven inflammatory pathologies.
2021-07-07 | GSE148577 | GEO
Project description:The nuclear factor-kB (NF-kB) family of transcription factors is important for hematopoietic function, including development, maintenance, and differentiation of different hematopoietic lineages in response to cytokines and infection. Although ligand-independent or basal NF-kB signaling is required for HSC homeostasis in the absence of inflammation, the upstream tonic mediators of NF-kB signaling are not known. Herein we describe TNF receptor associated factor 6 (TRAF6) as an essential regulator of HSC homeostasis by preserving self-renewal and quiescence through basal activation of NF-kB. Hematopoietic-specific deletion of Traf6 resulted in impaired HSC self-renewal and fitness. Gene expression, RNA splicing, and molecular analyses of Traf6-deficient HSPC revealed changes in adaptive immune signaling, innate immune signaling, and NF-kB signaling, indicating that signaling via TRAF6 in the absence of cytokine stimulation and/or infection occurs in HSPC and is required for HSC function. In addition, we established that loss of NF-kB signaling is responsible for the major hematopoietic defects observed in Traf6-deficient HSPC as deletion of IKKb similarly resulted in impaired HSC self-renewal and fitness. Taken together, our observations position TRAF6 as an essential regulator of HSC homeostasis by maintaining a minimal threshold level of IKKb/NF-kB signaling.
2018-01-31 | GSE109050 | GEO
Project description:<p>Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression, and rational therapy design. Here, we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-kB pathway in a total of 41% of cases including CYLD, TRAF3, NFKBIA and NLRC5. Functional analysis confirmed novel inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent member protein 1 (LMP1) functions to constitutively activate NF-kB signaling, and we observed mutual exclusivity among somatic NF-kB pathway aberrations and LMP1-overexpression, suggesting that NF-kB activation is selected for by both somatic and viral events during NPC pathogenesis.</p>
| phs001244 | dbGaP
Project description:Dysfunctional NF-kB signaling is critically involved in Inflammatory bowel disease (IBD). We investigated the mechanism by which RIPK1 and TRADD, two key mediators of NF-kB signaling, in mediating intestinal pathology using TAK1 IEC deficient model. We show that phosphorylation of TRADD by TAK1 modulates RIPK1-dependent apoptosis. TRADD and RIPK1 act cooperatively to mediate cell death mediated by TNF and TLR signaling. We demonstrate the pathological evolution from RIPK1-dependent ileitis to RIPK1- and TRADD-co-dependent colitis in TAK1 IEC deficient condition. Combined RIPK1 inhibition and TRADD knockout completely protect against intestinal pathology and lethality in TAK1 IEC KO mice. Furthermore, we identify distinctive microbiota dysbiosis biomarkers for RIPK1-dependent ileitis and TRADD-dependent colitis. These findings reveal the cooperation between RIPK1 and TRADD in mediating cell death and inflammation in IBD with NF-kB deficiency and suggest the possibility of combined RIPK1 kinase inhibition and TRADD knockout as a new therapeutic strategy for IBD.
2025-01-22 | GSE279702 | GEO
Project description:Dysfunctional NF-kB signaling is critically involved in Inflammatory bowel disease (IBD). We investigated the mechanism by which RIPK1 and TRADD, two key mediators of NF-kB signaling, in mediating intestinal pathology using TAK1 IEC deficient model. We show that phosphorylation of TRADD by TAK1 modulates RIPK1-dependent apoptosis. TRADD and RIPK1 act cooperatively to mediate cell death mediated by TNF and TLR signaling. We demonstrate the pathological evolution from RIPK1-dependent ileitis to RIPK1- and TRADD-co-dependent colitis in TAK1 IEC deficient condition. Combined RIPK1 inhibition and TRADD knockout completely protect against intestinal pathology and lethality in TAK1 IEC KO mice. Furthermore, we identify distinctive microbiota dysbiosis biomarkers for RIPK1-dependent ileitis and TRADD-dependent colitis. These findings reveal the cooperation between RIPK1 and TRADD in mediating cell death and inflammation in IBD with NF-kB deficiency and suggest the possibility of combined RIPK1 kinase inhibition and TRADD knockout as a new therapeutic strategy for IBD.
2025-01-22 | GSE279700 | GEO
Project description:Dysfunctional NF-kB signaling is critically involved in Inflammatory bowel disease (IBD). We investigated the mechanism by which RIPK1 and TRADD, two key mediators of NF-kB signaling, in mediating intestinal pathology using TAK1 IEC deficient model. We show that phosphorylation of TRADD by TAK1 modulates RIPK1-dependent apoptosis. TRADD and RIPK1 act cooperatively to mediate cell death mediated by TNF and TLR signaling. We demonstrate the pathological evolution from RIPK1-dependent ileitis to RIPK1- and TRADD-co-dependent colitis in TAK1 IEC deficient condition. Combined RIPK1 inhibition and TRADD knockout completely protect against intestinal pathology and lethality in TAK1 IEC KO mice. Furthermore, we identify distinctive microbiota dysbiosis biomarkers for RIPK1-dependent ileitis and TRADD-dependent colitis. These findings reveal the cooperation between RIPK1 and TRADD in mediating cell death and inflammation in IBD with NF-kB deficiency and suggest the possibility of combined RIPK1 kinase inhibition and TRADD knockout as a new therapeutic strategy for IBD.
2025-01-22 | GSE279034 | GEO
Project description:Chemoresistance and metastasis are the primary causes of mortality in patients with breast cancer. Here, we demonstrated that the metalloproteinase ADAMTS1 is upregulated in chemotherapy-treated and metastatic breast cancer samples. Mechanistically, the zymogen form of ADAMTS1 undergoes nuclear translocation via importin-dependent transport, where it cooperates with the SWI/SNF complex to activate a set of genes, including TBK1, STING, TRAF6, and MARCHF2, leading to STING ubiquitination and the non-classical cGAS-STING-NF-kB signaling activation, which in turn promotes chemoresistance and metastasis. Notably, long-term chemotherapy establishes a self-reinforcing loop by: (i) NF-kB/p65-mediated transcriptional induction of ADAMTS1, and (ii) MARCHF2-dependent ubiquitin-proteasomal degradation of FURIN, the protease responsible for ADAMTS1 maturation. This dual regulation results in nuclear accumulation of catalytically inactive ADAMTS1 zymogen. Clinical analyses have shown that high ADAMTS1 expression combined with low FURIN expression is strongly associated with poor patient prognosis. These results reveal a key role for the zymogen ADAMTS1 in inducing tumor chemoresistance and metastasis in response to long-term chemotherapy stimulation, supporting the use of its inhibitor melatonin as a therapeutic strategy in combination with chemotherapy for patients with breast cancer.
2025-09-04 | GSE307248 | GEO
Project description:Chemoresistance and metastasis are the primary causes of mortality in patients with breast cancer. Here, we demonstrated that the metalloproteinase ADAMTS1 is upregulated in chemotherapy-treated and metastatic breast cancer samples. Mechanistically, the zymogen form of ADAMTS1 undergoes nuclear translocation via importin-dependent transport, where it cooperates with the SWI/SNF complex to activate a set of genes, including TBK1, STING, TRAF6, and MARCHF2, leading to STING ubiquitination and the non-classical cGAS-STING-NF-kB signaling activation, which in turn promotes chemoresistance and metastasis. Notably, long-term chemotherapy establishes a self-reinforcing loop by: (i) NF-kB/p65-mediated transcriptional induction of ADAMTS1, and (ii) MARCHF2-dependent ubiquitin-proteasomal degradation of FURIN, the protease responsible for ADAMTS1 maturation. This dual regulation results in nuclear accumulation of catalytically inactive ADAMTS1 zymogen. Clinical analyses have shown that high ADAMTS1 expression combined with low FURIN expression is strongly associated with poor patient prognosis. These results reveal a key role for the zymogen ADAMTS1 in inducing tumor chemoresistance and metastasis in response to long-term chemotherapy stimulation, supporting the use of its inhibitor melatonin as a therapeutic strategy in combination with chemotherapy for patients with breast cancer.
2025-09-03 | GSE306824 | GEO
Project description:Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages. Comparison of unstimulated monocytes and macrophages, and flagellin stimulated monocytes and macrophages.
2010-07-07 | E-GEOD-22373 | biostudies-arrayexpress