Hepatic Huwe1 loss protects mice from non-alcoholic fatty liver disease through lipid metabolic rewiring
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1010463 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25782628_1.fastq.gz | Fastqsanger.gz | |||
| SRR25782628_2.fastq.gz | Fastqsanger.gz | |||
| SRR25782629_1.fastq.gz | Fastqsanger.gz | |||
| SRR25782629_2.fastq.gz | Fastqsanger.gz | |||
| SRR25782630_1.fastq.gz | Fastqsanger.gz |
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Project description:Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease worldwide and is estimated to affect nearly a third of the population. Huwe1, also known as ARF-BP1, MULE, and HectH9, is a HECT (homology to E6-APC terminus)-domain E3 ubiquitin ligase originally identified as a binding partner of the tumor suppressor ARF, as well as a direct negative regulator of the tumor suppressor p53. To further elucidate the in vivo role of Huwe1, we generated a liver-specific Huwe1 (Huwe1LKO) knockout mouse model. Surprisingly, liver-specific knockout of Huwe1 protected mice from the development of age-induced hepatic steatosis. To elucidate the mechanism underlying this phenotype, bulk RNAseq analysis was performed on liver tissues from 1-year-old Huwe1LKO and Huwe1WTmice.
2023-12-06 | GSE241875 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease worldwide and is estimated to affect nearly a third of the population. Huwe1, also known as ARF-BP1, MULE, and HectH9, is a HECT (homology to E6-APC terminus)-domain E3 ubiquitin ligase originally identified as a binding partner of the tumor suppressor ARF, as well as a direct negative regulator of the tumor suppressor p53. To further elucidate the in vivo role of Huwe1, we generated a liver-specific Huwe1 (Huwe1LKO) knockout mouse model. Surprisingly, liver-specific knockout of Huwe1 protected mice from the development of age-induced hepatic steatosis. To elucidate the mechanism underlying this phenotype, mass spectrometry analysis was performed on liver tissues from 1-year-old Huwe1LKO and Huwe1WT mice.
2024-01-26 | PXD045279 | Pride
Project description:ChREBPα protects against diet-induced non-alcoholic fatty liver disease
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Project description:Global gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis. Human liver samples of steatosis and non-alcoholic steatohepatitis were selected for RNA extraction and hybridization on Affymetrix microarrays. This dataset is part of the TransQST collection.
2014-11-07 | E-GEOD-63067 | biostudies-arrayexpress
Project description:Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARFBP1, MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells. MIZ1 and MYC ChIPseq experiments in HUWE1 inhibitor-treated Ls174T cells as well as RNAseq experiments in HUWE1- or MIZ1-depleted Ls174T cells after HUWE1 inhibitor treatment. Sequencing was performed on an Illumina Genome Analyzer IIx.
2014-10-21 | E-GEOD-59223 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes. There are 12 samples in our study which belonged to 4 groups, and each group contains 3 different samples.
2015-01-23 | E-GEOD-65220 | biostudies-arrayexpress
Project description:In this study, we explored the role of macrophage scavenger receptor 1 (MSR1) in the progression of non-alcoholic fatty liver disease. Mice lacking Msr1 proved to be protected against high fat-cholesterol diet (HFD)-induced metabolic disorder, showing fewer hepatic lipid-laden foamy macrophages, less hepatic inflammation and changed lipid metabolism.
2022-02-01 | GSE163471 | GEO
Project description:HUWE1 was depleted in Ls174T cells with an shRNA and the expression changes relative to a control shRNA were analyzed with microarray. Ls174T cells were treated with two separate HUWE1 inhibitor compounds (BI8622/BI8626) at concentrations of 20 uM and expression profiles relative to DMSO treated control were monitored via microarray. HUWE1-depleted Ls174T cells were treated with BI8622 (20uM) and expression profiles relative to BI8622-treated non-depleted cells were analyzed.
2014-10-22 | E-MTAB-1890 | biostudies-arrayexpress
Project description:Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII promotes activation of the ATM kinase at TRCs to drive DNA repair. We show the ATPase Wrnip1 that binds and protects stalled replication forks, associates with RNAPII and limits ATM activation. Wrnip1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase Huwe1. Mutation of Huwe1 promotes the transfer of Wrnip1 onto replisome and induces TRCs stimulating ATM activation on RNAPII. This mechanism is evoked early upon replicative stress to induce Wrnip1 translocation and ATM signaling at TRCs. Thus, although primarily considered as genotoxic events, TRCs can provide a mechanism to maintain genome stability under replicative stress.
2023-07-31 | PXD037677 | Pride
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