Liver-specific loss of the three TTP family proteins results in the development of hepatocellular carcinoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA687270 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13291348_1.fastq.gz | Fastqsanger.gz | |||
| SRR13291348_2.fastq.gz | Fastqsanger.gz | |||
| SRR13291349_1.fastq.gz | Fastqsanger.gz | |||
| SRR13291349_2.fastq.gz | Fastqsanger.gz | |||
| SRR13291350_1.fastq.gz | Fastqsanger.gz |
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Project description:The objective of this project is to identify the differential gene expression changes between WT and liver-specific knockout of the three TTP family proteins post HCC development
2021-01-01 | GSE163728 | GEO
Project description:Members of the tristetraprolin (TTP) family of RNA-binding proteins can bind to and promote the decay of specific transcripts containing AU-rich motifs. ZFP36 (TTP) is best known for regulating cytokine expression in myeloid cells; however, the mammalian paralogues ZFP36L1 and ZFP36L2 have not been viewed as important in controlling inflammation. To study potential functional overlaps of these three TTP family proteins in myeloid cells, we developed myeloid-specific knock-out (M-KO) mice of these genes, singly and together. M-Zfp36-KO mice exhibited a mild inflammatory syndrome late in life, while M-Zfp36l1-KO and M-Zfp36l2-KO mice had no apparent spontaneous phenotypes. Mice with simultaneous deficiency of all three TTP family members in myeloid cells developed a severe, spontaneous, inflammatory phenotype, with a median survival of 8 weeks. Macrophages derived from these mice contained many more stabilized transcripts than cells from M-Zfp36-KO mice, many encoding pro-inflammatory cytokines and chemokines. Our findings emphasize the importance of all three family members, acting in concert, in myeloid cell function.
2023-10-20 | GSE229923 | GEO
Project description:Tristetraprolin (TTP) is a tandem CCCH zinc finger protein that was identified through its rapid induction by mitogens in fibroblasts. Studies of TTP-deficient mice, and cells derived from them, showed that TTP could bind to certain AU-rich elements in mRNAs, leading to increases in the rates of mRNA deadenylation and destruction. Known physiological target mRNAs for TTP include tumor necrosis factor alpha (TNF), granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 2 beta (IL2 beta). Here we used microarray analysis of RNA from wild-type and TTP-deficient fibroblast cell lines to identify transcripts with different decay rates, after serum stimulation and actinomycin D treatment. Of 250 mRNAs apparently stabilized in the absence of TTP, 23 contained conserved TTP binding sites; 10 of these were shown by secondary analyses to be stabilized. The most dramatically affected transcript encoded the protein Ier3, recently implicated in the physiological control of blood pressure. The Ier3 transcript contained several conserved TTP binding sites that could bind TTP directly, and conferred TTP sensitivity to the mRNA in cell transfection studies. These studies have identified several new, physiologically relevant TTP target transcripts in fibroblasts; these target mRNAs encode proteins from a variety of functional classes. Keywords: mRNA degradation, time course, knockout experiment
2006-10-17 | GSE5324 | GEO
Project description:Members of the tristetraprolin (TTP) family of RNA-binding proteins can bind to and promote the decay of specific transcripts containing AU-rich motifs. ZFP36 (TTP) is best known for regulating cytokine expression in myeloid cells; however, the mammalian paralogues ZFP36L1 and ZFP36L2 have not been viewed as important in controlling inflammation. To study potential functional overlaps of these three TTP family proteins in myeloid cells, we developed myeloid-specific knock-out (M-KO) mice of these genes, singly and together. M-Zfp36-KO mice exhibited a mild inflammatory syndrome late in life, while M-Zfp36l1-KO and M-Zfp36l2-KO mice had no apparent spontaneous phenotypes. Mice with simultaneous deficiency of all three TTP family members in myeloid cells developed a severe, spontaneous, inflammatory phenotype, with a median survival of 8 weeks. Macrophages derived from these mice contained many more stabilized transcripts than cells from M-Zfp36-KO mice, many encoding pro-inflammatory cytokines and chemokines. Our findings emphasize the importance of all three family members, acting in concert, in myeloid cell function.
2023-10-20 | GSE229922 | GEO
Project description:Controlled decay of cytokine and chemokine mRNAs restrains the time and amplitude of inflammatory responses. Tristetraprolin (TTP) binds to AU-rich elements in 3´ untranslated regions of mRNA and targets the bound mRNA for degradation. We have addressed here the function of TTP in balancing the macrophage activation state by a comprehensive analysis of TTP-dependent mRNA decay in LPS-stimulated macrophages from WT and TTP-deficient mice.
2011-12-15 | GSE28880 | GEO
Project description:Tristetraprolin (TTP) binds to specific AU-rich elements in the 3'UTR of certain transcripts and regulates post-transcriptional gene expression by increasing the rate of mRNA turnover. Here, we generated a novel TTP mouse line (TTPΔARE) with a 136 base deletion in the 3'UTR AU-rich region of TTP mRNA, which resulted in a moderate increase in TTP protein expression in many tissues. In this study, we evaluated the effects of the moderate TTP overexpression on the overall pattern of gene expression in spleen, to investigate the effect of this mutation on mRNA targets of TTP under normal conditions. We utilized "TTPΔARE" (136 b deletion in the 3'UTR AU-rich region of Zfp36 mRNA) mice that overexpress TTP and compared the transcriptomic changes to the littermate "WT" mice. Spleen mRNA from four WT and four "TTPΔARE" mice were subjected to mRNA-Seq. All the animals used in this study were males between the ages of 8-12 weeks and were on a C57BL/6 background.
2019-01-19 | GSE65357 | GEO
Project description:Tristetraprolin (TTP) is a tandem CCCH zinc finger protein that was identified through its rapid induction by mitogens in fibroblasts. Studies of TTP-deficient mice, and cells derived from them, showed that TTP could bind to certain AU-rich elements in mRNAs, leading to increases in the rates of mRNA deadenylation and destruction. Known physiological target; mRNAs for TTP include tumor necrosis factor alpha (TNF), granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 2 beta (IL2 beta). Here we used microarray analysis of RNA from wild-type and TTP-deficient fibroblast cell lines to identify transcripts with different decay rates, after serum stimulation and actinomycin D treatment. Of 250 mRNAs apparently stabilized in the absence of TTP, 23 contained conserved TTP binding sites; 10 of these were shown by secondary analyses to be stabilized. The most dramatically affected transcript encoded the protein Ier3, recently implicated in the physiological control of blood pressure. The Ier3 transcript contained several conserved TTP binding sites that could bind TTP directly, and conferred TTP sensitivity to the mRNA in cell transfection studies. These studies have identified several new, physiologically relevant TTP target transcripts in fibroblasts; these target mRNAs encode proteins from a variety of functional classes. Experiment Overall Design: Cell lines were derived from mouse embryonic fibroblast (MEF) cultures from littermate E14.5 embryos (for Zfp36 +/+ and -/- cells). MEFs were maintained at 37o C (5% CO2) in DMEM containing 10% FBS, 100 Experiment Overall Design: U/ml penicillin, 100 μg/ml streptomycin and 2 mM L-glutamine. When the cells had reached approximately 70-90 % confluence, they were trypsinized and diluted 2-50 fold in the same medium, based on morphology and growth rate, such that they would reach near confluence in 3-4 days when subcultured. Experiment Overall Design: Five identical experiments involving sequential serum deprivation, serum stimulation and actinomycin D treatment were performed on five different days; each experiment involved simultaneous identical experiments with the WT and KO cell lines. In each experiment, the cells were serum deprived for 16h, and a sample was taken at that point as a serum-deprived control. The cells were then stimulated by 10% FBS for Experiment Overall Design: 90 min and another sample taken, after which 5μg/ml actinomycin D was added; samples for RNA analysis were then removed at 30, 60, 90 and 120 min after actinomycin D treatment. In all experiments, each sample represented three combined 100 mm dishes of cells.
2008-11-22 | E-GEOD-5324 | biostudies-arrayexpress
Project description:Controlled decay of cytokine and chemokine mRNAs restrains the time and amplitude of inflammatory responses. Tristetraprolin (TTP) binds to AU-rich elements in 3´ untranslated regions of mRNA and targets the bound mRNA for degradation. We have addressed here the function of TTP in balancing the macrophage activation state by a comprehensive analysis of TTP-dependent mRNA decay in LPS-stimulated macrophages from WT and TTP-deficient mice. We compared mRNA stability in LPS-treated BMDMs from WT and TTP-/- mice by microarray-based measurement of the remnant mRNA after transcriptional blockade with actinomycin D (act D). To increase the sensitivity of the mRNA decay profiling we inhibited the LPS-activated p38 MAPK with the specific inhibitor SB203580 since p38 MAPK negatively regulates the mRNA-destabilizing activity of TTP. LPS stimulation was for 3h before addition of act D. RNA was harvested at 0', 45' and 90' thereafter.
2011-12-15 | E-GEOD-28880 | biostudies-arrayexpress
Project description:In order to examine the effects of bone marrow TTP deficiency on inflammation and lipid metabolism and determine the driving force during atherosclerosis, 8 week-old female LDLR−/− mice on C57BL/6J background were lethally irradiated and reconstituted with a wild type (TTP+/+) or TTP knockout (TTP−/−) bone marrow cells and fed a Western diet for 12 weeks. Then mice were sacrificed and tissues were collected for analysis. Liver tissues were collected and gene expression was analysed using a whole genome microarray. Bone marrow TTP−/− recipients displayed a significantly higher systemic and multi-organ inflammation compared to the BM-TTP+/+ recipients. BM-TTP−/− mice displayed a significant reduction of serum lipid levels, attenuated hepatic steatosis, and decreased lipid excretion than the control mice. microarray data showed that BM-TTP deficiency modulate liver genes involved in lipid metabolism and inflammatory response. RT-qPCR was used to confirm the results in several genes from microarray data. BM-TTP deficiency did not further accelerate atherorogenesis process in LDLR−/− mice after a Western diet feeding. TTP promoted VLDL to drive proinflammatory mechanism into proatherogenic mechanism.
2019-08-12 | GSE126481 | GEO
Project description:This study sought correlates of relapse tendency in TTP by examining gene expression profiles in peripheral blood leukocytes from patients with acquired ADAMTS13-deficient TTP in remission and matched healthy controls for global gene expression and autoantibodies. Total RNA was isolated from PAXgene RNA tubes from 39 patients with with acquired ADAMTS13-deficient TTP (all patients had relapsed) and 39 healthy controls.
2013-03-07 | E-GEOD-36418 | biostudies-arrayexpress