Exposure of squamous esophageal cell line HET-1A to deoxycholic acid (DCA)
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Shane Duggan
PROVIDER: E-GEOD-13378 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrettâs metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisons with data derived from gene expression studies of Barrettâs esophagus and associated adenocarcinoma. SKGT4 cells were exposed to 300um DCA over 24 hours in duplicate experiments including matched timepoint controls. RNA samples were taken at 4, 8, 12 and 24 hours from DCA (DCA) exposed and resting (REST) timepoint controls.
2010-02-28 | E-GEOD-13376 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE13376: Exposure of Barrett's associated adenocarcinoma cell lines SKGT4 to deoxycholic acid (DCA) GSE13378: Exposure of squamous esophageal cell line HET-1A to deoxycholic acid (DCA) Refer to individual Series
2010-03-02 | E-GEOD-13400 | biostudies-arrayexpress
Project description:The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrett’s metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisions with data derived from gene expression studies of Barrett’s esophagus and associated adenocarcinoma. Additionally this study may be used to assess divergence in response to bile acids by comparisons with similar study performed in SKGT4 barrett''s assocaited adenocarcinoma cell line.
2010-02-20 | GSE13378 | GEO
Project description:The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrett’s metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisons with data derived from gene expression studies of Barrett’s esophagus and associated adenocarcinoma.
2010-02-20 | GSE13376 | GEO
Project description:The major aetiological risk factor for Barrett's oesophagus and oesophageal adenocarcinoma is gastroesophageal reflux. This study's aim was to identify genes involved in the celular response to reflux in vitro. The Barrettâ??s oesophagus cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5; 152 genes were up-regulated at 2 hours (91 at 6 hours) and 10 down-regulated at 2 hours (34 at 6 hours). 12 genes were identified and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma; Background and Aims: The major etiological risk factor for Barrettâ??s esophagus and esophageal adenocarcinoma is gastro-esophageal reflux. This studyâ??s aim was to identify genes involved in the cellular response to components of reflux both in vitro and in patients with reflux-related disease. Methods: The Barrettâ??s cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. 12 genes of interest were analysed by Real Time PCR both in cell line and biopsies from 110 patients with non-erosive reflux disease, esophagitis, Barrettâ??s esophagus and esophageal adenocarcinoma. Results: In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5. Of 12 genes analysed in biopsies, 10 were significantly different between the 4 groups with the largest change for anterior gradient homolog 2, which may modulate p53 function. This had highest expression in biopsies from Barrettâ??s esophagus (median gene fold change for Barrettâ??s esophagus versus non-erosive reflux disease, 411.2 (95% CI 290.5-682.7; p<0.01); esophageal adenocarcinoma versus non-erosive reflux disease 68.1 (20.5-161.4; p<0.01)). In addition 4 genes associated with development/differentiation were upregulated in Barrettâ??s biopsies compared to those from non-erosive reflux disease (SEL1L, MFNG, CRIP1 and EFNA1). Conclusions: Novel genes have been identified, whose expression is altered after acid and bile exposure in vitro and in biopsies from patients with reflux related diseases. These genes may have utility as biomarkers of response to reflux and should be assessed in prospective studies. Experiment Overall Design: The Barrett's oesophagus cell line CP-A hTERT was treated with a 15 minute exposure of acid (pH 4.5), a mixture of primary bile acids (pH 4.5) or deoxycholic acid (pH 4.5). RNA extraction occurred in treatment and non-treated cells at 2 hours and 6 hours. The treatments were performed in duplicate on 2 different days. RNA was compared in each treatment to each control at the relevant time points, in a 2 x 2 manner by using Affymetrex U133 Plus 2.0 arrays. Results of 12 genes were confirmed by Real Time PCR and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma.
2008-06-16 | E-GEOD-9768 | biostudies-arrayexpress
Project description:Deoxycholic acid (DCA) is a secondary bile acid produced by a small number of commensal species of bacteria present in the mammalian gut. Elevated DCA concentration correlates with disease states including colon cancer and cholesterol gallstones, but the associated mechanisms are not fully understood. Both primary and secondary bile acids are also capable of affecting gene expression through nuclear receptors such as FXR. To better understand the impact of a commensal-derived secondary bile acid on host metabolism we fed DCA to germ-free (GF) mice, which normally lack DCA, and compared the hepatic transcriptomes of bile acid fed GF mice to GF mice receiving a control diet, as well as to those of conventionally housed control animals. Interestingly, the feeding of DCA to GF mice, but not the feeding of cholic acid (CA) from which DCA is derived, results in an up-regulation of genes of cholesterol biosynthetic pathways. GF mice normally have elevated hepatic cholesterol compared to conventionally housed mice. Despite increase in the expression of cholesterol biosynthetic genes, the DCA fed GF mice showed a markedly decreased level of hepatic cholesterol equivalent to the hepatic cholesterol concentration of conventionally colonized animals. Total cholesterol in the serum was unaffected by DCA, but there was a decrease in the HDL lipoprotein fraction as well as an increase in the non-HDL lipoprotein fraction of the serum cholesterol. DCA, but not CA, is sufficient to modulate host lipoprotein metabolism. Taken together, these results suggests that a minor component of the gut microbiome has a significant impact on cholesterol homeostasis through secondary metabolism of bile acids and suggests a possible therapeutic intervention route through the microbial metabolic pathways. two mouse strains, three diets, one time point
2015-01-08 | E-GEOD-34730 | biostudies-arrayexpress
Project description:In order to successfully survive in and to colonize the gastrointestinal tract, bacteria need to develop strategies to overcome bile acid stress. The most prominent bile acids are the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) as well as the secondary bile acid deoxycholic acid (DCA). In this study, we investigated the stress response of E. faecalis and E. faecium to sublethal concentrations of these three bile acids on the proteome level using DIA-MS. As both species showed similar IC50 for DCA and CDCA in growth experiments and both were highly resistant towards CA, we assumed similar changes to their protein expression profiles. Moreover, we investigated proteomic differences of E. faecalis grown under aerobic or microaerophilic conditions. Our findings showed similarities, but also species-specific variations in the response to the different bile acids, which reveal potential differences in the adaptation process. DCA and CDCA had a strong effect on down-expression of proteins involved in translation, transcription and replication in E. faecalis, but to a lesser extent in E. faecium. Proteins commonly significantly altered in their expression in all bile acid treated samples were identified for both species and represent a “general bile acid response”. Among these, ABC-transporters, multi-drug transporters and proteins related to cell wall biogenesis were up-expressed in both species and thus seem to play an essential role in bile acid resistance. Specific for all E. faecalis samples was the up-expression of several subunits of a V-type ATPase and the down-expression of proteins involved in pyruvate-, citrate- and folate metabolism. Most of the differentially expressed proteins were also identified when E. faecalis was incubated with low levels of DCA at microaerophilic conditions in comparison to aerobic conditions, indicating that adaptations to bile acids and to a microaerophilic atmosphere can occur simultaneously.
2024-02-15 | PXD040819 | Pride
Project description:Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide, with most of the case occurrences in developed regions. CRC can be induced by luminal factors, like dietary components and bile acids. Bile acids are metabolized from cholesterol in the liver, stored in the gallbladder and released into the small intestine upon meal ingestion to facilitate the absorption of dietary lipids and lipid-soluble vitamins. Bile acids are effectively reabsorbed at the distal ileum and returned to the liver, and only a small portion (~2-5%) enters the colon. Here primary bile acids, like cholic acid (CA) and chenodeoxycholic acid (CDCA) are deconjugated by bacteria and secondary bile acids are formed, such as deoxycholic acid (DCA), ursodeoxycholic acid (UDCA) and lithocholic acid. DCA is the major component of the colonic bile acid pool and is found to be increased upon a high fat diet. Moreover, high levels of DCA are known to increase the risk of colorectal cancer by inducing cytotoxicity to epithelial cells. In this study the cytotoxicity of Caco-2 cells to stimulation with cholic acid is investigated.
2021-10-01 | GSE120699 | GEO
Project description:The progression of myocardial infarction (MI) involves multiple metabolic disorders. Bile acid metabolites have been increasingly recognized as pleiotropic signalling molecules that regulate multiple cardiovascular functions. G protein-coupled bile acid receptor (TGR5) is one of the receptors sensing bile acids to mediate their biological functions. In this study, we aimed to elucidate the effects of bile acids-TGR5 signaling pathways in myocardial infarction (MI).Mice underwent either the LAD ligation model of MI or sham operation. Both MI and sham mice were gavaged with 10 mg/kg/d DCA or vehicle control since 3-day before the operation. Administration of DCA improved cardiac function at the 3th-day post-MI. The effects of DCA in the heart were determined by RNA-sequencing experiments.
2020-09-24 | GSE158415 | GEO
Project description:Metabolic products of the microbiota can alter hematopoiesis. However, the contribution and site of action of bile acids is poorly understood. Here we demonstrate that the secondary bile acids, deoxycholic acid (DCA), and lithocholic acid (LCA) increase bone marrow myelopoiesis. Treatment of bone marrow cells with DCA and LCA preferentially expanded immunophenotypic and functional (CFU-GM) granulocyte-monocyte progenitors (GMPs). DCA treatment of sorted hematopoietic stem/progenitor cells (HSPCs) increased CFU-GMs, indicating that direct exposure of HSPCs to DCA sufficed to expand GMPs. We determined that the vitamin D receptor (VDR) was required for the DCA-induced increase in CFU-GMs and GMPs. Finally, single-cell RNA sequencing revealed that DCA significantly upregulated genes associated with myeloid differentiation and proliferation in GMPs. The action of DCA on HSPCs to expand GMPs in a VDR-dependent manner suggests a mechanism for how microbiome-host interactions may directly impact bone marrow hematopoiesis and the severity of infectious and inflammatory disease.
2023-07-01 | GSE215639 | GEO