Mus musculus
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ABSTRACT:
PROVIDER: PRJNA107673 | ENA |
REPOSITORIES: ENA
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Project description:Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have anti-oxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Mdr1a-/- mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet-gene interactions and potential effects of foods on remission or development of IBD. This study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a-/- mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0.2% curcumin or control + 0.1% rutin and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a-/- mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways probably mediated by PXR and PPARï¡ activation of RXR. These results reveal the potential of global gene expression and pathway analyses to study and better understand the effect of foods in colonic inflammation. Experiment Overall Design: Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0â¢2% curcumin or control + 0â¢1% rutin and monitored from the age of 7 to 24 weeks. As only curcumin significantly reduced colonic HIS, comparison of the gene expression levels in colon was carried out using total RNA from colon tissue of four mdr1a-/- mice from the control group (high HIS) and four mdr1a-/- mice from the curcumin group (low HIS). A reference design with eight arrays was used for this comparison, where each individual RNA sample was hybridized in the array with the reference RNA, totalizing 4 biological replicates per treatment.
2008-06-11 | E-GEOD-10684 | biostudies-arrayexpress
Project description:Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have anti-oxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Mdr1a-/- mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet-gene interactions and potential effects of foods on remission or development of IBD. This study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a-/- mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0.2% curcumin or control + 0.1% rutin and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a-/- mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways probably mediated by PXR and PPARalpha activation of RXR. These results reveal the potential of global gene expression and pathway analyses to study and better understand the effect of foods in colonic inflammation. Keywords: Colonic inflammation, gene expression, curcumin, rutin, genome-wide microarrays
2008-04-10 | GSE10684 | GEO
Project description:This study assessed gene expression changes associated with inflammation in the colon tissue of multi-drug resistance targeted mutation (Mdr1a-/-) mice, a model of human IBD. It also tested the anti-inflammatory potential of curcumin in the colon of these mice with a particular focus on the proteome. A colonic histological injury score was determined for each mouse to assess the level of colon inflammation in Mdr1a-/- mice, and to establish the effect of curcumin on inflammation. Insights into mechanisms of colonic inflammation in the Mdr1a-/- mice were gained using transcriptome (microarray) and proteome (2-D gel electrophoresis and LCMS protein identification) analyses. These data were compared to changes in the colon proteome in response to curcumin, and to previously described transcriptomic analyses [Nones et al, PMID: 18761777; GSE10684] in response to curcumin, in this model.
2014-10-02 | GSE61939 | GEO
Project description:This study assessed gene expression changes associated with inflammation in the colon tissue of multi-drug resistance targeted mutation (Mdr1a-/-) mice, a model of human IBD. It also tested the anti-inflammatory potential of curcumin in the colon of these mice with a particular focus on the proteome. A colonic histological injury score was determined for each mouse to assess the level of colon inflammation in Mdr1a-/- mice, and to establish the effect of curcumin on inflammation. Insights into mechanisms of colonic inflammation in the Mdr1a-/- mice were gained using transcriptome (microarray) and proteome (2-D gel electrophoresis and LCMS protein identification) analyses. These data were compared to changes in the colon proteome in response to curcumin, and to previously described transcriptomic analyses [Nones et al, PMID: 18761777; GSE10684] in response to curcumin, in this model. A total of 24 male Mdr1a-/- mice, and 24 male FVB/N mice, purchased from Taconic (Hudson, NY, USA) at 4-5 weeks of age, were used for this study. 12 mice were randomly assigned to each of two different dietary groups: control (AIN-76A powdered diet), or curcumin (AIN-76A + 0.2% curcumin). At 21 and 24 weeks of age, mice were euthanized and colon samples taken for histological, microarray, and proteomics analyses. The total histology score (HIS) in the colon was determined according to previously described criteria. Total RNA was isolated using TRIzolM-BM-. reagent. Colon RNA from four Mdr1a-/- mice (with high HIS) on the control diet (i.e. AIN-76A powdered diet) was compared with colon RNA from four FVB/N mice with low HIS also on the control diet (i.e. AIN-76A powdered diet). All individual RNA samples were hybridized against a common reference RNA on separate slides. The reference RNA was prepared using equimolar RNA extracts from small intestine, colon, kidney and liver of normal healthy growing Swiss mice plus RNA extracts from Swiss mouse fetuses. These data were compared with previously reported transcriptomics analysis of colon RNA from the same four Mdr1a-/- mice on the AIN-76A diet (with high HIS) compared with colon RNA from four Mdr1a-/- mice on the curcumin diet (with low HIS; Nones et al 2009, PMID: 18761777)
2014-10-02 | E-GEOD-61939 | biostudies-arrayexpress
Project description:This study tested the anti-inflammatory potential of a green tea extract rich in polyphenols (GrTP) in the colon of the multi-drug resistance targeted mutation (Mdr1a-/-) mouse model of IBD. A colonic histological injury score was determined for each mouse to establish the effect of GrTP on inflammation. Insights into mechanisms responsible for changes in inflammation were gained using transcriptome (microarray) and proteome (2-D gel electrophoresis and LCMS protein identification) analyses. A total of 24 male Mdr1a-/- mice purchased from Taconic (Hudson, NY, USA) at 4-5 weeks of age were used for this study. 12 mice were randomly assigned to each of two different dietary groups: control (AIN-76A powdered diet), or GrTP (AIN-76A + 0.6% green tea polyphenol). At 21 and 24 weeks of age, mice were euthanized and colon samples taken for histological and microarray analyses. The total histology score (HIS) in the colon was determined according to previously described criteria. Total RNA was isolated using TRIzol reagent. Colon RNA from four Mdr1a-/- mice on the GrTP diet (with low HIS) was compared with colon RNA from four Mdr1a-/- mice on the AIN-76A diet (with high HIS). All individual RNA samples were hybridized against a common reference RNA on separate slides. The reference RNA was prepared using equimolar RNA extracts from small intestine, colon, kidney and liver of normal healthy growing Swiss mice plus RNA extracts from Swiss mouse fetuses.
2012-10-18 | E-GEOD-41644 | biostudies-arrayexpress
Project description:This study tested the anti-inflammatory potential of a green tea extract rich in polyphenols (GrTP) in the colon of the multi-drug resistance targeted mutation (Mdr1a-/-) mouse model of IBD. A colonic histological injury score was determined for each mouse to establish the effect of GrTP on inflammation. Insights into mechanisms responsible for changes in inflammation were gained using transcriptome (microarray) and proteome (2-D gel electrophoresis and LCMS protein identification) analyses.
2012-10-18 | GSE41644 | GEO
Project description:Human Ulcerative colitis (UC) is characterized by chronic colonic inflammation and has been associated with an increased risk of colorectal carcinoma. Gene and protein expression profiles of ABCB1/MDR1 have been shown to be dysregulated in UC and sporadic colorectal cancer. We demonstrated that in a murine model of colitis-associated tumorigenesis, MDR1A KO mice showed reduced tumor load when compared to wildtype (WT) mice. The aim of this study was to identify gene alterations in colitis-associated tumors in the context of MDR1A deficiency. We used microarrays to assess gene expression profiles of colitis-associated colonic tumors from WT or MDR1A KO mice.
2017-06-17 | GSE94960 | GEO
Project description:Effects of dietary curcumin on the colon proteome and transcriptome in the Mdr1a-/- mouse model of inflammatory bowel disease
| PRJNA262719 | ENA
Project description:Inflammatory bowel disease (IBD) is associated with altered microbiota composition and metabolism, but it is unclear whether these changes precede inflammation or are the result of it since current studies have mainly focused on changes after the onset of disease. We previously showed differences in mucus gut microbiota composition preceded colitis-induced inflammation and stool microbial differences only became apparent at colitis onset. In the present study, we aimed to investigate whether microbial dysbiosis was associated with differences in both predicted microbial gene content and endogenous metabolite profiles. We examined the functional potential of mucus and stool microbial communities in the mdr1a -/- mouse model of colitis and littermate controls using PICRUSt on 16S rRNA sequencing data. Our findings indicate that despite changes in microbial composition, microbial functional pathways were stable before and during the development of mucosal inflammation. LC-MS-based metabolic phenotyping (metabotyping) in urine samples confirmed that metabolite profiles in mdr1a -/- mice were remarkably unaffected by development of intestinal inflammation and there were no differences in previously published metabolic markers of IBD. Metabolic profiles did, however, discriminate the colitis-prone mdr1a -/- genotype from controls. Our results indicate resilience of the metabolic network irrespective of inflammation. Importantly as metabolites differentiated genotype, genotype-differentiating metabolites could potentially predict IBD risk.
2017-07-14 | MTBLS432 | MetaboLights
Project description:Inflammatory Bowel Disease (IBD) is a term describing a collection of conditions characterised by chronic inflammatory disorder of the gastrointestinal tract involving an inappropriate immune response to commensal microorganisms in a genetically susceptible host. Four kiwifruit extracts, aqueous and ethyl acetate extracts of gold kiwifruit (Actinidia chinensis) or green kiwifruit (A. deliciosa), have previously demonstrated anti-inflammatory activity using in vitro models of IBD. This study examined whether these kiwifruit extracts had immune modulating effects in vivo against inflammatory processes known to be increased in patients with IBD. KFEs were used as a dietary intervention in Il10-/- mice (an in vivo model of IBD) and the C57BL/6J background strain in a 3 x 2 factorial design. While all Il10-/- mice developed significant colonic inflammation compared to the C57BL/6J mice, this was not affected by the inclusion of KFE in the diet. Whole genome gene and protein expression level profiling indicated that KFEs influenced immune signalling pathways and metabolic processes within the colonic tissue; however, the effects were subtle. In particular, adaptive immune pathways were reduced by three out of four kiwifruit extracts, with greater reduction seen in the C57BL/6J mice. This suggests that while immune-modulating activity was present in vivo, KFEs did not reduce inflammatory processes relevant to IBD. SUBMITTER_CITATION: Edmunds, Shelley Jane. The effects of kiwifruit extracts on gene and protein expression in in vitro and in vivo mouse models of inflammatory bowel disease. Diss. University of Auckland, New Zealand, 2010. http://hdl.handle.net/2292/6623
2011-03-05 | GSE27684 | GEO