Expression data from the mouse liver with constitutively active NF-kB
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE28085 | GEO | 2012/04/01
SECONDARY ACCESSION(S): PRJNA139735
REPOSITORIES: GEO
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Project description:Activation of hepatic NF-kB signaling induces inflammation and ultimately fibrosis. To investigate the underlying mechanism, we used microarrays to detail the global programme of gene expression which is regulated by hepatic NF-kB signaling. We generated transgenic mice which express a constitutively active IKK2 controlled under the LAP promotor. The liver samples were collected from transgenic mice as well as from control animals at the age of 4 weeks. RNA extraction was performed from these liver samples and hybridized on Affymetrix microarrays.
2012-03-31 | E-GEOD-28085 | biostudies-arrayexpress
Project description:Abstract. Deregulated c-MYC is found in a variety of cancers where it promotes proliferation as well as apoptosis. In many hematological malignancies enhanced NF-kB exerts prosurvival functions. Here we investigated the role of NF-kB in mouse and human c-MYC-transformed lymphomas. The NF-kB-pathway is extinguished in murine lymphoma cells and extrinsic stimuli typically inducing NF-kB activity fail to activate this pathway. Genetic activation of the NF-kB pathway induces apoptosis in these cells, while inhibition of NF-kB by an IkBa superrepressor provides a selective advantage in vivo. Furthermore, in human Burkitt´s lymphoma cells we find that NF-kB activation induces apoptosis. NF-kB upregulates Fas and predisposes to Fas-induced cell death, which is caspase 8 mediated and can be prevented by CFLAR overexpression. We conclude that c-MYC overexpression sensitizes cells to NF-kB-induced apoptosis and persistent inacvtivity of NF-kB signaling is a prerequisite for MYC-mediated tumorigenesis. We could also show that low immunogenicity and Fas insensitivity of MYC driven lymphoma cells is reversed by activation of NF-kB. Our observations provide a molecular explanation for the described absence of the NF-kB signaling in Burkitt´s lymphoma and question the applicability of NF-kB inhibitors as candidates for treatment of this cancer.
2009-07-22 | GSE17129 | GEO
Project description:Stringent regulation of TNF signaling prevents aberrant inflammation. TNF engages the canonical NF-kB pathway for activating the RelA:p50 heterodimer, which mediates specific expressions of pro-inflammatory and immune response genes. Importantly, the NF-kB system discriminates between time-varied TNF inputs. Negative feedback regulators of the canonical pathway, including IkBa, thought to ensure transient RelA:p50 responses to brief TNF stimulations. The noncanonical NF-kB pathway controls a separate RelB activity associated with immune differentiation. In a systems modeling approach, we uncovered an unexpected role of p100, a constituent of the noncanonical pathway, in TNF signaling. Brief TNF stimulation of p100-deficient cells produced an additional late NF-kB activity composed of the RelB:p50 heterodimer, which distorted the TNF-induced gene-expression program. Periodic TNF pulses augmented this RelB:p50 activity, which was reinforced by NF-kB-dependent RelB synthesis. In sum, the NF-kB system seems to engage distantly related molecular species for enforcing dynamical and gene controls of immune-activating TNF signaling.
2020-08-22 | GSE119961 | GEO
Project description:The nuclear factor kB (NF-kB) subunits RelA, RelB, c-Rel, p50 and p52 are each critical for B-cell development and function. To systematically characterize their responses to canonical and non-canonical NF-kB pathways activity, we performed ChIP-seq analysis in lymphoblastoid B-cells. We found a surprisingly complex NF-kB binding landscape, which did not readily reflect the two NF-kB pathway paradigm. Instead, ten subunit binding patterns were observed at promoters and eleven at enhancers. Surprisingly, nearly one-third of NF-kB binding sites lacked kB motifs. De novo motif finding uncovered distinct modes of NF-kB recruitment at these sites. The oncogenic forkhead box protein FOXM1 and NF-kB co-occupied many kB sites despite the absence of a FOXM1 DNA motif. FoxM1 knockdown decreased expression of key NF-kB targets and caused apoptosis. Our study highlights opportunities for selective therapeutic NF-kB blockade. ChIP-seq was used to define the genomic landscape of NF-kB DNA binding in lymphoblastoid cells.
2014-08-29 | E-GEOD-55105 | biostudies-arrayexpress
Project description:To address the role of NF-kB in aging in vivo, we utilized a well-characterized system that allows inducible and site-specific inhibition of NF-kB activity in murine skin. The hormone binding domain of the mutant estrogen receptor that is responsive to 4-hydroxytamoxifen (4-OHT) was fused to a mutant of p50 (IDNkB, inducible dominant negative NF-kB) that dimerizes with other NF-kB subunits but is unable to bind DNA, thus dominantly inhibiting NF-kB activity. Expression was driven within the basal layer of murine epidermis by the keratin 14 promoter in transgenic mice. To test whether NF-kB activity is required to maintain age-associated gene expression, we applied topical 4-OHT and ethanol vehicle (EtOH) for two weeks to the right (R) and left (L) dorsal flanks, respectively, of chronologically aged transgenic mice (O, 18-23 months). Young transgenic mice (Y, 1 month) were treated in parallel as control. Skin samples were harvested and analyzed for gene expression using mouse cDNA microarrays containing 35,217 elements, representing 18,880 unique genes. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set Computed
2010-06-30 | E-GEOD-3845 | biostudies-arrayexpress
Project description:Activation of hepatic FoxO3 signaling induces hyperglycemia and hyperinsulinemia. Metformin administration reverses FoxO3-induced phenotype development. To investigate the underlying mechanism, we used microarrays to detail the global programme of gene expression which is regulated by hepatic FoxO3 signaling.
2019-02-22 | GSE44977 | GEO
Project description:The nuclear factor kB (NF-kB) subunits RelA, RelB, c-Rel, p50 and p52 are each critical for B-cell development and function. To systematically characterize their responses to canonical and non-canonical NF-kB pathways activity, we performed ChIP-seq analysis in lymphoblastoid B-cells. We found a surprisingly complex NF-kB binding landscape, which did not readily reflect the two NF-kB pathway paradigm. Instead, ten subunit binding patterns were observed at promoters and eleven at enhancers. Surprisingly, nearly one-third of NF-kB binding sites lacked kB motifs. De novo motif finding uncovered distinct modes of NF-kB recruitment at these sites. The oncogenic forkhead box protein FOXM1 and NF-kB co-occupied many kB sites despite the absence of a FOXM1 DNA motif. FoxM1 knockdown decreased expression of key NF-kB targets and caused apoptosis. Our study highlights opportunities for selective therapeutic NF-kB blockade.
2014-08-29 | GSE55105 | GEO
Project description:Background: Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. Metastasis and relapse are the leading causes of death in MB patients. The initiation of the SHH subgroup of MB (SHH-MB) is due to the aberrant activation of Sonic Hedgehog (Shh) signaling. However, the mechanisms for its metastasis are still unknown. Results: AMP-dependent protein kinase (AMPK) restrains the activation of Shh signaling pathway, thereby impeding the proliferation of SHH-MB cells. More importantly, AMPK also hinders the growth and metastasis of SHH-MB cells by regulating NF-kB signaling pathway. Furthermore, Vismodegib and TPCA-1, which block the Shh and NF-kB pathways, respectively, synergistically restrained the growth, migration, and invasion of SHH-MB cells. Conclusions: This work demonstrates that AMPK functions through two signaling pathways, SHH-GLI1 and NF-kB. AMPK-NF-kB axis is a potential target for molecular therapy of SHH-MB, and the combinational blockade of NF-kB and Shh pathways confers synergy for SHH-MB therapy.
2023-07-01 | GSE218076 | GEO
Project description:To address the role of NF-kB in aging in vivo, we utilized a well-characterized system that allows inducible and site-specific inhibition of NF-kB activity in murine skin. The hormone binding domain of the mutant estrogen receptor that is responsive to 4-hydroxytamoxifen (4-OHT) was fused to a mutant of p50 (IDNkB, inducible dominant negative NF-kB) that dimerizes with other NF-kB subunits but is unable to bind DNA, thus dominantly inhibiting NF-kB activity. Expression was driven within the basal layer of murine epidermis by the keratin 14 promoter in transgenic mice. To test whether NF-kB activity is required to maintain age-associated gene expression, we applied topical 4-OHT and ethanol vehicle (EtOH) for two weeks to the right (R) and left (L) dorsal flanks, respectively, of chronologically aged transgenic mice (O, 18-23 months). Young transgenic mice (Y, 1 month) were treated in parallel as control. Skin samples were harvested and analyzed for gene expression using mouse cDNA microarrays containing 35,217 elements, representing 18,880 unique genes. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2007-12-01 | GSE3845 | GEO