Expression profiles of miRNAs in cholestasis mice and normal mice.
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PROVIDER: PRJNA692429 | ENA |
REPOSITORIES: ENA
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Project description:We report differences in miRNA expression between cholestasis mice and LIX1L knockout cholestasis mice.Liver samples were obtained from mice from different groups, and the liver samples were detected using the Agilent Mouse miRNA Microarray, Release 21.0 (8*60K,Design ID:070155) chip. After the samples were qualitatively controlled, the data were standardized using the Quantile algorithm. According to the analysis confirmation, a total of three groups of differences were compared and the corresponding GO and KEGG were performed.miR-191-3p displayed the most significant reduction in the liver of WT-BDL mice, and the reduced expression of miR-191-3p was restored in Lix1l-/--BDL mice. We demonstrated that miR-191-3p targets and downregulates LRH-1.Finally, we demonstrated that miR-191-3p further alleviated cholestatic liver injury by inhibiting the expression of LRH-1 to inhibit bile acid synthesis.This study provides a reference for the application of a comprehensive miRNA Microarray to characterize differential miRNA expression in cholestasis mice.
2021-01-16 | GSE164903 | GEO
Project description:Viral miRNAs alter cellular miRNAs profiles
| PRJNA421000 | ENA
Project description:Aims Biliary diseases represent around 10% of all chronic liver diseases and affect both adults and children. Currently available biochemical tests detect cholestasis but not early liver fibrosis. Circulating extracellular vesicles (EVs) provide a real-time molecular snapshot of the injured organ in a non-invasive way. We thus aimed at searching for a panel of EV-based biomarkers for cholestasis-induced early liver fibrosis using mice models. Results: Progressive and detectable histological evidence of collagen deposition and liver fibrosis was observed as from Day 8 after bile duct ligation (BDL) in mice. Whole transcriptome and small RNA-seq analyses of circulating EVs revealed differentially enriched RNA species after BDL versus sham controls. Unsupervised hierarchical clustering identified a signature that allowed for discrimination between BDL and controls. In particular, 151 microRNAs enriched in BDL-derived EVs were identified, of which 66 were conserved in humans. The liver was an important source of circulating EVs in BDL animals as evidenced by the enrichment of several hepatic mRNAs, such as Albumin, Haptoglobin, Transferrin receptor 1 and Alas2. Interestingly, among experimentally validated miRNAs, miR194-5p and miR29-3p showed similar enrichment patterns also in EVs derived from DDC-treated (drug-induced cholestasis) and MDR2-/- (genetic cholestasis) mice. Innovation A panel of mRNAs and miRNAs contained in circulating EVs, when combined, provides sensitive biomarkers for the early detection of hepatic damage and fibrosis. Conclusion Analysis of EVs for enrichment in miR29-3p and miR194-5p, in combination with hepatic injury RNA markers, could represent a sensitive biomarker panel for the early detection of cholestasis-induced liver fibrosis.
2022-02-28 | GSE166753 | GEO
Project description:Aims Biliary diseases represent around 10% of all chronic liver diseases and affect both adults and children. Currently available biochemical tests detect cholestasis but not early liver fibrosis. Circulating extracellular vesicles (EVs) provide a real-time molecular snapshot of the injured organ in a non-invasive way. We thus aimed at searching for a panel of EV-based biomarkers for cholestasis-induced early liver fibrosis using mice models. Results: Progressive and detectable histological evidence of collagen deposition and liver fibrosis was observed as from Day 8 after bile duct ligation (BDL) in mice. Whole transcriptome and small RNA-seq analyses of circulating EVs revealed differentially enriched RNA species after BDL versus sham controls. Unsupervised hierarchical clustering identified a signature that allowed for discrimination between BDL and controls. In particular, 151 microRNAs enriched in BDL-derived EVs were identified, of which 66 were conserved in humans. The liver was an important source of circulating EVs in BDL animals as evidenced by the enrichment of several hepatic mRNAs, such as Albumin, Haptoglobin, Transferrin receptor 1 and Alas2. Interestingly, among experimentally validated miRNAs, miR194-5p and miR29-3p showed similar enrichment patterns also in EVs derived from DDC-treated (drug-induced cholestasis) and MDR2-/- (genetic cholestasis) mice. Innovation A panel of mRNAs and miRNAs contained in circulating EVs, when combined, provides sensitive biomarkers for the early detection of hepatic damage and fibrosis. Conclusion Analysis of EVs for enrichment in miR29-3p and miR194-5p, in combination with hepatic injury RNA markers, could represent a sensitive biomarker panel for the early detection of cholestasis-induced liver fibrosis.
2022-02-28 | GSE166752 | GEO
Project description:Mechanism-based toxicogenomics (tgx) is used as a tool to identify markers reflective of the onset and progression of cholestasis in C57BL/6 mice using Cyclosporin A (CsA) as a model compound. Critical doses for tgx analysis were derived from a dose range finding study in which increase of serum cholesterol, total bile acids, and total bilirubin as well as induction of hepatocyte vacuolization 25 days upon repeated CsA administration through oral gavage were considered as critical effects. For tgx analysis to find early markers, livers of mice repeatedly treated with 3 mg/kg BW, 8.9 mg/kg BW, and 26.7 mg/kg BW for one, four, and eleven days were collected.
2013-07-11 | GSE31540 | GEO
Project description:Mechanism-based toxicogenomics (tgx) is used as a tool to identify markers reflective of the onset and progression of cholestasis in C57BL/6 mice using Cyclosporin A (CsA) as a model compound. Critical doses for tgx analysis were derived from a dose range finding study in which increase of serum cholesterol, total bile acids, and total bilirubin as well as induction of hepatocyte vacuolization 25 days upon repeated CsA administration through oral gavage were considered as critical effects. For tgx analysis to find early markers, livers of mice repeatedly treated with 3 mg/kg BW, 8.9 mg/kg BW, and 26.7 mg/kg BW for one, four, and eleven days were collected. 60 samples are analyzed; per treatment duration (1, 4, 11 days), time-matched vehicle (olive oil) controls and three dose groups (3, 8.9, 26.7 mg/kg BW) were included; each group consisted of 5 replicates; 3 arrays were excluded, 2 because of quality control restrictions, 1 because of outlier properties. 2 that failed QC are omitted. Final data consists of 58 CEL files.
2013-07-11 | E-GEOD-31540 | biostudies-arrayexpress
Project description:Recently, study on circulating microRNAs (miRNAs) as potential biomarkers of drug-induced liver injury (DILI), has received increasing attention. It has been demonstrated that miR-122 and miR-192, which are liver enriched, could be potential biomarkers of DILI, however, these miRNAs cannot discern types of injuries. In the present study, we comprehensively analyzed time-dependent plasma miRNA profiles in rats with drug- or chemical-induced hepatocellular injury, cholestasis, and steatosis with high-throughput miRNA sequencing. To enable comparison of miRNA expression levels between DILI models with different severity and peaks of injuries, stages of injury were defined as early, middle and late, according to cluster patterns of miRNA expression profiles. Through differential analysis, we characterized miRNAs that were specifically up- or down-regulated in each DILI model. Interestingly, several miRNAs were dramatically changed earlier than traditional biomarkers such as ALT and AST. For example, in APAP-induced hepatocellular injury model, let-7b-5p was up-regulated as early as 3 h after dosing, while significant change in ALT level was observed at 24 h. Thereafter, we focused on the DILI type-specific miRNAs which were up-regulated at early stage of injury. RT-qPCR study validated that let-7b-5p and miR-1-3p for hepatocellular injury, miR-143-3p and miR-218a-5p for cholestasis, and miR-320-3p for steatosis models have shown significant increase in the early stage of the injuries. The present study suggests the utility of miRNAs as specific biomarkers for early detection of DILI.
2018-09-26 | GSE112934 | GEO
Project description:The liver is the central organ critically regulating the balance of the metabolically potent yet toxic bile acids in the body. While genomic association studies have pointed to hepatic Sel1L – a critical component of mammalian Hrd1 ER-associated degradation (ERAD) machinery – as an influencer of serum bile acid levels, physiological relevance and mechanistic insights of ERAD in bile homeostasis remain unexplored. Using hepatocyte-specific Sel1L-deficient mouse models, we report that hepatic Sel1L-Hrd1 ERAD critically manages bile homeostasis in the body. Mice with hepatocyte-specific Sel1L developed intrahepatic cholestasis, with significant overload of bile acids in the liver and circulation under basal condition, and were hypersensitive to dietary bile acid challenge. By contrast, biliary bile acid and phosphatidylcholine levels were reduced, pointing to an export defect from hepatocytes. Unbiased proteomics analysis followed by biochemical assays revealed significant accumulation of the bile-stabilizing phosphatidylcholine exporter ATP-binding cassette 4 (Abcb4) in the ER of Sel1L-deficient livers, a gene associated with Progressive Familial Intrahepatic Cholestasis type III. Indeed, Abcb4 was a substrate of Sel1L-Hrd1 ERAD. Hence, hepatic Sel1L-Hrd1 ERAD maintains bile equilibrium via quality control of Abcb4 maturation in the ER.
2023-03-11 | PXD035243 | Pride
Project description:Cholestasis is characterized by disrupted bile flow from the liver to the small intestine. Although etiologically different cholestasis display similar symptoms, diverse factors can contribute to the progression of the disease and determines the appropriate therapeutic option. Therefore, stratifying cholestatic patients is essential for the development of tailor-made treatment strategies. Here, we have analyzed the liver proteome from cholestatic patients of different etiology. 7,161 proteins were identified and quantified, of which 263 were differentially expressed between control and cholestasis groups. These differential proteins point to deregulated cellular processes that explain part of the molecular framework of cholestasis progression. However, the clustering of different cholestasis types was limited. Therefore, a machine learning pipeline was designed to identify a panel of 20 differential proteins that segregate different cholestasis groups with high accuracy and sensitivity. In summary, proteomics combined with machine learning algorithms provides valuable insights into the molecular mechanisms of cholestasis progression and a panel of proteins to discriminate across different types of cholestasis. This strategy may prove useful to develop precision medicine approaches for patient care.
2024-05-22 | PXD047823 | Pride
Project description:Increasing studies suggested the treatment potential of mesenchymal stem cells in variety diseases. Evidence showed that MSCs could promote injured tissue repair and improve disease mortality. These indicated that MSC transplantation may be an ideal candidate for cholestasis treatment.We found that MenSC transplantation could significantly improve the symptoms and pathological changes of DDC-induced cholestasis liver injury in mice.
2022-02-16 | PXD028425 | Pride