Effects of JNK on TGF-beta responses of mouse B lymphoma derived A20 cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE7503 | GEO | 2007/08/01
SECONDARY ACCESSION(S): PRJNA100489
REPOSITORIES: GEO
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Project description:TGF-beta plays multiple functions in a board range of cellular responses such as proliferation, differentiation, motility and survival by activating several cellular signaling pathways, including Smads and MAP kinases (Erk, JNK and p38). In particular, TGF-beta can activate pro- or anti-apoptotic signals depending on the target cells. We found that blockage of JNK activation sensitized mouse B lymphoma derived A20 cells to TGF-beta-induced apoptosis. These results suggest that TGF-beta activate JNK to inhibit the activation of death signal that is simultaneously activated by TGF-beta. We used microarrays to gain insight into the effects of JNK inhibition on gene expression in TGF-b-stimulated A20 cells and identified JNK-dependent TGF-beta inducible genes. Experiment Overall Design: The following six samples were prepared: untreated A20 cells (non-stimulated, DMSO): A20 cells cultured with SP600125 for 24 h (non-stimulated, SP600125): A20 cells stimulated with TGF-beta for 12 h (TGF-beta 12 h, DMSO) and 24 h (TGF-beta 24 h, DMSO): and A20 cells stimulated with TGF-beta in the presence of SP600125 for 12 h (TGF-beta 12 h, SP600125) and 24 h (TGF-beta 24 h, SP600125), respectively. Total RNA was prepared and hybridized to the Affymetrix Mouse Genome 430 2.0 array. Genes whose expression was increased by more than 2-fold at either 12 or 24 h after TGF-beta stimulation were identified as TGF-beta inducible genes. Amongst them, we identified genes whose induction levels were reduced by more than 75% by co-treatment with the JNK inhibitor SP600125.
2008-06-15 | E-GEOD-7503 | biostudies-arrayexpress
Project description:Genome wide transcriptional profiling on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.bgalactosidase transduced livers, before and 24 hours after 78% extended liver resection. Overexpression of the NF-kB inhibitory protein A20 improves recovery of liver function and mass following extended liver resection and severe liver ischemia reperfusion injury in mice. In this project, we explored effects of A20 using transcriptional profiling on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.bgalactosidase transduced livers, before and 24 hours after 78% extended liver resection. A20 or beta-galactosidase gene expression in the mouse liver was achieved by penile vein injection of 1x109 pfu of rAd. in 100uL of normal saline, which results in optimal transgene expression 5 days after injection in 30% to 40% of hepatocytes (Longo et al, 2005). Extended (78%) LR, consisting of resection of the lateral, medial, left, and right lobes, was performed 5 days following rAd. administration in 8-week old BALB/c mice weighing 25 to 30 grams (Taconic, Germantown, NY), as described (Longo et al, 2005). RNA was extracted from the resected portion of the liver (before samples) and from the remnant liver 24 hours after resection (after samples). RNA from three animals was pooled per microarray and 2 microarrays per group were performed.
2010-09-18 | E-GEOD-24203 | biostudies-arrayexpress
Project description:Purpose: The purpose of this study is to investigate role of JNK signaling during EMT. Method: Transcriptome of TGF-b treated NmuMG cells along with DMSO and JNKi treated NMuMG was generated using next generation high throughput sequencing in triplicates and duplicates respectively. Reads were mapped using Tophat and transcript abundance and differential expression was calculated using HTSeq-Count and DESeq programs. Results: Using time course RNA-Seq data, we uncover a large number of coding and noncoding RNAs that are modulated during stepwise progression of TGF-β-induced EMT. Concomitant with their activation behavior, Smad and JNK pathway are required for onset and progression of EMT respectively, a finding that was also confirmed in patients. Transcriptome analysis further revealed a progressive dependency of EMT on JNK signaling. Conclusion: We identified several novel transcription factors that require JNK signaling for their enhanced expression upon EMT and show that depletion of these factors during EMT hampers acquisition of transcriptional and phenotypic changes hallmark of this process. These factors are similarly induced during neurogenesis, a process also involving JNK activation and EMT.
2015-07-13 | GSE54133 | GEO
Project description:A20 is a negative regulator of NF-κB signaling, crucial to control inflammatory responses and ensure tissue homeostasis. A20 is thought to restrict NF-κB activation both by its ubiquitin-editing activity as by non-enzymatic activities. Besides its role in NF-κB signaling, A20 also acts as a protective factor inhibiting apoptosis and necroptosis. Because of the ability of A20 to both ubiquitinate and deubiquitinate substrates and its involvement in many cellular processes, we hypothesized that deletion of A20 might generally impact on protein levels, thereby disrupting cellular processes. We performed a differential proteomics study of bone marrow derived macrophages (BMDMs) from control and myeloid-specific A20 knockout mice, both in untreated conditions and after LPS and TNF treatment, and demonstrate proteome-wide changes in protein expression upon A20 deletion. Several inflammatory proteins are up-regulated in the absence of A20, even without an inflammatory stimulus. Depending on the treatment and the time, more proteins are regulated. Together these changes may affect multiple signaling pathways disturbing tissue homeostasis and inducing (autoimmune) inflammation, as suggested by genetic studies in patients.
2018-05-15 | PXD008726 | Pride
Project description:Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappa B, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease entity. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal (EMZL), nodal (NMZL) and splenic (SMZL) MZLs. Inactivating mutations encoding truncated A20 proteins were identified in 6/32 (18.8%) MZLs, including 3/11 (27.3%) EMZLs, 2/9 (22.2%) NMZLs, and 1/12 (8.3%) SMZLs. Two additional unmutated non-splenic MZLs also showed mono- or biallelic A20 deletions by FISH and/or array-CGH. Thus, A20 loss by both somatic mutations and/or deletions represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-kappa B activation. Keywords: Genome variation profiling by SNP array 27 MZL samples. No technical replications.
2009-04-01 | E-GEOD-13989 | biostudies-arrayexpress
Project description:Purpose: The purpose of this study is to investigate role of JNK signaling during EMT. Method: Transcriptome of TGF-b treated NmuMG cells along with DMSO and JNKi treated NMuMG was generated using next generation high throughput sequencing in triplicates and duplicates respectively. Reads were mapped using Tophat and transcript abundance and differential expression was calculated using HTSeq-Count and DESeq programs. Results: Using time course RNA-Seq data, we uncover a large number of coding and noncoding RNAs that are modulated during stepwise progression of TGF-?-induced EMT. Concomitant with their activation behavior, Smad and JNK pathway are required for onset and progression of EMT respectively, a finding that was also confirmed in patients. Transcriptome analysis further revealed a progressive dependency of EMT on JNK signaling. Conclusion: We identified several novel transcription factors that require JNK signaling for their enhanced expression upon EMT and show that depletion of these factors during EMT hampers acquisition of transcriptional and phenotypic changes hallmark of this process. These factors are similarly induced during neurogenesis, a process also involving JNK activation and EMT. Transcriptome of TGF-b treated NmuMG cells along with DMSO and JNKi treated NMuMG was generated using next generation high throughput sequencing in triplicates and duplicates respectively.
2015-07-13 | E-GEOD-54133 | biostudies-arrayexpress
Project description:Objectives: Genetic variations in TNFAIP3 (A20) de-ubiquitinase (DUB) domain increase the risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis. A20 is a negative regulator of NF-κB but the role of its DUB domain and related genetic variants remain unclear. We aimed to study the functional effects of A20 DUB-domain alterations in immune cells and understand its link to SLE pathogenesis. Methods: CRISPR/Cas9 was used to generate human U937 monocytes with A20 DUB-inactivating C103A knock-in mutation. Whole genome RNA-sequencing was used to identify differentially expressed genes between WT and C103A knock-in cells. Functional studies were performed in A20 C103A U937 cells and in immune cells from A20 C103A mice and genotyped healthy individuals with A20 DUB polymorphism rs2230926. Neutrophil extracellular trap (NET) formation was adressed ex vivo in neutrophils from A20 C103A mice and SLE-patients with rs2230926. Results: Genetic disruption of A20 DUB domain in human and murine myeoloid cells did not give rise to enhanced NF-κB signaling. Instead, cells with C103A mutation or rs2230926 polymorphism presented an upregulated expression of PADI4, an enzyme regulating protein citrullination and NET formation, two key mechanisms in autoimmune pathology. A20 C103A cells exhibited enhanced protein citrullination and extracellular trap formation, which could be suppressed by selective PAD4 inhibition. Moreover, SLE-patients with rs2230926 showed increased NETs and increased frequency of autoantibodies to citrullinated epitopes. Conclusions: We propose that genetic alterations disrupting the A20 DUB domain mediate increased susceptibility to SLE through the upregulation of PADI4 with resultant protein citrullination and extracellular trap formation.
2019-07-10 | GSE116780 | GEO
Project description:Effects of JNK on TGF-beta responses of mouse B lymphoma derived A20 cells
| PRJNA100489 | ENA
Project description:Purpose: The goals of this study are to compare the transcriptome profiling (RNA-seq) of different A20 expression in HCT116 cells, to find potiential target genes for A20 mediated immnue escape. Results: There were 352 genes altered after A20 was knocked out with the log-fold >2 or <-2 compared to WT cells, and p value<0.01 . And 143 genes changed after rescued the expression of A20 in A20-KO cells compared to A20-KO cells. Among these altered genes, 13 genes were changes consistently. Conclusion:Gain- and loss-A20 functional studies proved that A20 could decrease the ¡°eat-me¡± signal calreticulin (CRT) protein on cell membranes via stabilizing stanniocalcin 1 (STC1). Mechanistically, A20 inhibited the degradation of STC1 protein which could capture the CRT inside cell rather than to translocated to cell membrane.
2023-08-30 | GSE206390 | GEO
Project description:Genome wide transcriptional profiling on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.bgalactosidase transduced livers, before and 24 hours after 78% extended liver resection. Overexpression of the NF-kB inhibitory protein A20 improves recovery of liver function and mass following extended liver resection and severe liver ischemia reperfusion injury in mice. In this project, we explored effects of A20 using transcriptional profiling on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.bgalactosidase transduced livers, before and 24 hours after 78% extended liver resection.
2010-09-18 | GSE24203 | GEO