Ena-DATASET-KCL-CS-01-04-2014-19:21:08:940-7 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001000811 | EGA |
REPOSITORIES: EGA
Publications
Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency.
Iannelli Fabio F Collino Agnese A Sinha Shruti S Radaelli Enrico E Nicoli Paola P D'Antiga Lorenzo L Sonzogni Aurelio A Faivre Jamila J Buendia Marie Annick MA Sturm Ekkehard E Thompson Richard J RJ Knisely A S AS Natoli Gioacchino G Ghisletti Serena S Ciccarelli Francesca D FD
Nature communications 20140513
Hepatocellular carcinoma (HCC) is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is unclear. Here we map acquired genomic alterations in human and mouse HCCs induced by defects in hepatocyte biliary transporters, which expose hepatocytes to bile salts and cause chronic inflammation that develops into cancer. In both human and mouse cancer genomes, we find few somatic point mutations with no impairment o ...[more]
Similar Datasets
Project description:SNP array of 7 HCCs and matched background liver in children with bile salt export pump deficiency
| EGAD00010000560 | EGA
Project description:Massive gene amplification drives pediatric hepatocellular carcinoma caused by bile salt export pump deficiency
| PRJNA243011 | ENA
Project description:Enterohemorrhagic Escherichia coli (EHEC), including serotype O157:H7, cause severe food-borne illness. On route to the human colon, they encounter and resist, numerous anti-microbial ingestion stresses. We hypothesize that these stresses cue EHEC to alter virulence properties. This study investigated the impact of bile salts on virulence properties and examined the genetic basis of the phenotypes. Established assays were used to examine adhesion to human epithelial cells, motility, verotoxin (VT) production and antimicrobial resistance with/without bile salt stress. Bacteria treated for 90 minute in DMEM plus 0.15% (w/v) bile salt mix demonstrated significantly enhanced adhesion to epithelial cells and resistance to several antibiotics but did not increase motility or VT production. To determine the genetic basis of these phenotypes a microarray experiment was conducted. EHEC strain 86-24, in mid-log phase of growth, were grown in DMEM pH 7.4 (control), or DMEM plus bile salt mix (0.15% w/v), for 90 minutes, statically at 37˚C, 5% CO2 prior to harvesting RNA for the microarray study. Four biological replicates were produced for each treatment. Microarray and gene expression analysis (semi-quantitative RT-PCR and beta-galactosidase reporter assays) of bile salt-treated EHEC revealed significant up-regulation of genes for lipid A modification, fimbriae, an efflux pump, and a two-component regulatory system relative to the bacteria grown in DMEM alone. This work points to several mechanisms that EHEC employs to resist the stresses of the human small intestine, notably efflux, antimicrobial resistance, and outer membrane alterations. Bile salts enhanced the virulence-related properties of increased adhesion and resistance to antimicrobials but not VT production or motility. This research contributes to our understanding of how EHEC senses and responds to host environmental signals and the mechanisms this pathogen uses to successfully colonize and infect the human host. Bacteria were grown in LB broth overnight with shaking, then subcultured into DMEM and grown statically at 37˚C, 5%CO2 to mid-log phase. Bacteria were then subjected to one of two 90 minute treatments: 1) Control: DMEM pH 7.4, or 2) Bile Salt Stress: DMEM pH 7.4 plus 0.15%, grown statically at 37˚C, 5%CO2.
2011-09-05 | E-GEOD-22060 | biostudies-arrayexpress
Project description:Hepatic cell lines serve as economical and reproducible alternatives for primary human hepatocytes. However, the utility of hepatic cell lines to examine bile acid homeostasis and cholestatic toxicity is limited due to abnormal expression and function of bile acid-metabolizing enzymes, transporters, and the absence of canalicular formation. Previously, addition of dexamethasone (DEX) and Matrigel™ overlay restored expression, localization, and function of the bile salt export pump (BSEP), and formation of bile canalicular-like structures in four-week cultures of HuH-7 human hepatoma cells. We present here an improved differentiation process with the addition of 0.5% dimethyl sulfoxide (DMSO), which increased the expression and function of the major bile acid uptake and efflux transporters, sodium taurocholate co-transporting polypeptide (NTCP) and BSEP, respectively, in two-week HuH-7 cell cultures. This in vitro model was further characterized for expression of cytochrome P450 enzymes (CYP450s), uridine 5'-diphospho-glucuronosyltransferase (UGTs) and transporters using quantitative targeted proteomics.
2022-10-14 | PXD031731 | Pride
Project description:Enterohemorrhagic Escherichia coli (EHEC), including serotype O157:H7, cause severe food-borne illness. On route to the human colon, they encounter and resist, numerous anti-microbial ingestion stresses. We hypothesize that these stresses cue EHEC to alter virulence properties. This study investigated the impact of bile salts on virulence properties and examined the genetic basis of the phenotypes. Established assays were used to examine adhesion to human epithelial cells, motility, verotoxin (VT) production and antimicrobial resistance with/without bile salt stress. Bacteria treated for 90 minute in DMEM plus 0.15% (w/v) bile salt mix demonstrated significantly enhanced adhesion to epithelial cells and resistance to several antibiotics but did not increase motility or VT production. To determine the genetic basis of these phenotypes a microarray experiment was conducted. EHEC strain 86-24, in mid-log phase of growth, were grown in DMEM pH 7.4 (control), or DMEM plus bile salt mix (0.15% w/v), for 90 minutes, statically at 37˚C, 5% CO2 prior to harvesting RNA for the microarray study. Four biological replicates were produced for each treatment. Microarray and gene expression analysis (semi-quantitative RT-PCR and beta-galactosidase reporter assays) of bile salt-treated EHEC revealed significant up-regulation of genes for lipid A modification, fimbriae, an efflux pump, and a two-component regulatory system relative to the bacteria grown in DMEM alone. This work points to several mechanisms that EHEC employs to resist the stresses of the human small intestine, notably efflux, antimicrobial resistance, and outer membrane alterations. Bile salts enhanced the virulence-related properties of increased adhesion and resistance to antimicrobials but not VT production or motility. This research contributes to our understanding of how EHEC senses and responds to host environmental signals and the mechanisms this pathogen uses to successfully colonize and infect the human host.
2011-09-06 | GSE22060 | GEO
Project description:Effect of bile salt export pump (Bsep) loss on LPS induced liver injury in mice
| PRJNA794745 | ENA
Project description:Chimeric mice with humanized livers are considered a useful animal model for predicting human drug metabolism and toxicity. In this study, the characteristics of fresh h-hepatocytes (cFHHs, PXB-cells®) isolated from chimeric mice (PXB-mice®) were evaluated in vitro to confirm their utility for drug development. The cFHHs cultured at high density (2.13 × 10^5 cells/cm2) displayed stable production of human albumin and cytochrome P450 (CYP) 3A activities for at least 21 days. The mRNA expression levels of 10 of 13 CYPs, UDP-glucuronosyltransferase (UGP), and transporters were maintained at >10% of the levels of freshly isolated cFHHs after 21 days. From 7-days cultured cFHHs at high density, many bile canaliculi were observed between cFHHs, and the accumulation of multidrug resistance-associated protein (MRP2) and bile salt export pump (BSEP) substrates in these bile canaliculi was clearly inhibited by cyclosporin A. We used microarrays to elucidate global gene expressions underlying this higher hepatic functions of high density cultured cFHHs (PXB-cells). Microarray analysis revealed that high density cultured cFHHs maintained high expressions of some transcription factors (HNF4α, PXR, and FXR) perhaps involved in the high CYP, UGT and transporter gene expressions of cFHHs.
2020-08-07 | GSE153298 | GEO
Project description:The study is about the role of Bacteroides thetaiotaomicron in the human gut microbiota, specifically its ability to form biofilms in response to bile salts. The study found that bile induces the expression of certain efflux pumps, and inhibiting these pumps impairs biofilm formation. Among the induced pumps, the BipABC pump is crucial for biofilm formation as it is involved in the efflux of magnesium, which affects the biofilm's extracellular matrix and structure. This discovery sheds light on how intestinal chemical cues, like bile salts, regulate biofilm formation in B. thetaiotaomicron, a significant gut symbiont.
2024-03-19 | E-MTAB-13460 | biostudies-arrayexpress
Project description:ABSTRACT Background & aims: The role of the intestine in the maintenance of cholesterol homeostasis is increasingly recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport (RCT) pathway, to which both biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway are,however, poorly understood. In the current study we aimed to identify treatment modalities that stimulate TICE and to uncover underlying driving mechanisms. Methods: TICE was assessed in a panel of knock-out and transgenic mice as well as in mice treated with the FXR agonist PX20606 either or not combined with the cholesterol absorption inhibitor ezetimibe. Results: We show that TICE is regulated by intestinal farnesoid X receptor (FXR) via its target fibroblast growth factor 15/19 (FGF15/19) and that the pathway can be stimulated to such an extent that mice excrete ~60% of their total cholesterol content each day. Both PX20606 and FGF19 increased the muricholate/cholate ratio in bile, inducing a more hydrophilic bile salt pool. The altered bile salt pool robustly stimulated secretion of cholesterol into the intestinal lumen via the sterol exporting heterodimer ATP binding cassette subfamily G member 5/8 (ABCG5/G8). Of note, we demonstrate that the increase in TICE induced by PX20206 is independent of changes in cholesterol absorption. Conclusions: Hydrophilicity of the bile salt pool, controlled by FXR and FGF15/19, is an important determinant of cholesterol removal via TICE. Translation of these results to humans may offer new treatment modalities for prevention of cardiovascular disease.
2017-01-10 | GSE74101 | GEO