ZFP36L1 Regulates Fgf21 mRNA Turnover and Modulates Alcoholic Hepatic Steatosis and Inflammation in Mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE163444 | GEO | 2021/01/01
REPOSITORIES: GEO
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Project description:ZFP36L1 post-transcriptionally regulates Fgf21 and modulates the pathogenesis of alcoholic hepatic steatosis and inflammation
| PRJNA686111 | ENA
Project description:To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR), we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages. Five-week-old C3H/HeN female mice (CLEA, Japan) were acclimated to the maintenance condition (25°C, 8:00-20:00 day / 20:00-8:00 night cycle and 35~40 % humidity), fed a CE-2 diet (CLEA, Japan), and given water ad libitum for one week. Each group of mice (n=4 for wild type mice analysis and n=3 for CAR decficient mice analysis) was fed Lieber's isocaloric diet (Oriental yeast, Japan) containing water, containing ethanol, containing ethanol and ellagic acid (Fluka Biochemika, Switzerland), or containing ethanol and trans-resveratrol (Sigma, USA) (Supplementary Table 1) for one week at 10:00 ad libitum. Then, the mice were fed each diet at 12 g / day for four weeks (Supplementary Fig. 1A). The approximate intake of each polyphenol was 50 mg / kg body weight / day. At 10:00 of the final day of the experimental period, the animals were anesthetized by diethyl ether, sacrificed by cervial fracture, and the heart blood, and the liver were collected.
2014-02-01 | E-GEOD-52644 | biostudies-arrayexpress
Project description:To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR), we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages.
2014-02-01 | GSE52644 | GEO
Project description:ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved Adenylate-Uridylate-rich Elements (AREs) located in 3' untranslated regions (UTRs) to mediate RNA decay. We hypothesized that ZFP36L1 is a negative regulator of a post-transcriptional hub involved in the RNA half-life regulation of cancer-related transcripts. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo; whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wildtype and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells ± tet-on ZFP36L1, was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1, including HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3' UTRs of these targets for RNA degradation, thus suppressing their expression. Collectively, our findings reveal an indispensable role of ZFP36L1 as a post-transcriptional safeguard against aberrant hypoxic signaling and abnormal cell cycle progression.
2020-10-02 | GSE136180 | GEO
Project description:High-throughput sequencing analysis of transcriptome from LPS-activated B cells from Lymph node of Zfp36l1(fl/fl) and Zfp36l1(fl/fl) x Cd79a(Cre/+) mice
2020-11-20 | GSE146073 | GEO
Project description:We report our study of the function of two members of the TTP (tristetraprolin) mRNA binding protein family, Zfp36l1 and Zfp36l2, in retinal development. We found that Zfp36l1 and Zfp36l2 were expressed in retinal progenitor cells during development and Müller glial cells and photoreceptors in the mature retina. Our analysis of the mutant retinas showed that, whereas the single knockout retinas appeared largely normal, the double knockout (DKO) retina manifested decreased RPC proliferation and increased differentiation of multiple retinal cell types. RNA-seq analysis not only confirmed the imbalance of proliferation and differentiation in the DKO retina but also revealed Zfp36l1 and Zfp36l2 interact with multiple signaling pathways including the sonic hedgehog pathway and the Notch pathway, to regulate this process.
2021-09-01 | GSE158718 | GEO
Project description:ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved Adenylate-Uridylate-rich Elements (AREs) located in 3' untranslated regions (UTRs) to mediate RNA decay. We hypothesized that ZFP36L1 is a negative regulator of a post-transcriptional hub involved in the RNA half-life regulation of cancer-related transcripts. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo; whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wildtype and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells ± tet-on ZFP36L1, was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1, including HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3' UTRs of these targets for RNA degradation, thus suppressing their expression. Collectively, our findings reveal an indispensable role of ZFP36L1 as a post-transcriptional safeguard against aberrant hypoxic signaling and abnormal cell cycle progression.
2020-10-02 | GSE136181 | GEO
Project description:Alcohol induced fatty liver cause a dangerous health problem and is the major cause of morbidity and mortality worldwide. Garlic (Allium sativum) is documented to possess anti-fatty liver properties. However the exact molecular mechanisms are unknown. The main aim of this experiment is to elucidate the underlying pathways through which garlic ameliorates alcohol induced fatty liver. Dially disulfide and garlic oil were the garlic compounds used in this study. Leiber DeCarli ethanol liquid diet was to induce fatty liver in C57BL/6 mice model. Also the expression impaired by alcohol induced fatty liver is another aim of this study. Leiber-Decarli ethanol diet was used to induce fatty liver in male C57BL/6 mice (n=12). For control, Lieber-DeCarli liquid control diet was fed to mice (n=4). The control mice were pair-fed to the ethanol mice. After adaptation, the ethanol fed mice were divided into three groups viz. alcohol (n=4), dially disulfide [DADS] (n=4) and garlic oil [GO] (n=4). The study started with the administration of DADS (15 mg/kg bw) or GO (50 mg/kg bw) mixed in 0.1 ml olive oil through gavage. For the control and alcohol groups, same amount of olive oil (0.1 ml) was gavaged. The mice were gavaged daily for 4 weeks. The mice were euthanized by CO2 and blood was collected by cardiac puncture. Liver, kidney, spleen, lungs and hearts were collected and their weights recorded. A portion of liver was snap frozen in liquid nitrogen (200 mg) for RNA extraction.
2012-10-01 | E-GEOD-40334 | biostudies-arrayexpress
Project description:We expressed either a wt or a phosphomutant version of ZFP36L1 in IMR90 ER:RAS cells. 7 days upon RAS induction (when the cells reach a fully senescent phenotype) we collected the RNA. ZFP36L1 is a RNA binding protein that binds to AU-rich elements in the 3âUTR of mRNAs and triggers their degradation. Our previous experiments showed that the activity of ZFP36L1 was key in the regulation of the senescent phenotype.By performing RNAseq we have uncovered the effect of expressing a constitutively active mutant of ZFP36L1 within the senescent transcriptome. 4 samples examined: Non-senescent cells (EV - 4OHT), Senescent cells (EV + 4OHT), Senescent cells expressing ZFP36L1wt and Senescent cells expressing ZFP36L1mut
2015-07-07 | E-GEOD-61130 | biostudies-arrayexpress