Effects of dietary curcumin on the colon proteome and transcriptome in the Mdr1a-/- mouse model of inflammatory bowel disease
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE61939 | GEO | 2014/10/02
SECONDARY ACCESSION(S): PRJNA262719
REPOSITORIES: GEO
Similar Datasets
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: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 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: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: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:Curcumin is a potent anti-inflammatory compound capable of preventing chemically induced colitis in mice. We used microarray analysis to detail the global programme of colonic gene expression in BALB/c mice fed standard or 2% curcumin-supplemented diet and treated with control or TNBS (trnitrobenzene-sulfonic acid, 2 mg/mouse) enema. Keywords: Diet and disease effect. 6-8 week old BALB/c mice were treated with respective diet two days prior to enema administration (day 0) and sacrificed on day 7. Whole colon was dissected from mice and their wild-type littermates and total RNA isolated for microarray analysis using Affymetrix murine MOE430 mouse array set. RNA was pooled from 3 mice in each dietary/treatment group.
2008-11-21 | E-GEOD-13705 | biostudies-arrayexpress
Project description:Curcumin is a potent anti-inflammatory compound capable of preventing chemically induced colitis in mice. We used microarray analysis to detail the global programme of colonic gene expression in BALB/c mice fed standard or 2% curcumin-supplemented diet and treated with control or TNBS (trnitrobenzene-sulfonic acid, 2 mg/mouse) enema. Keywords: Diet and disease effect.
2008-11-22 | GSE13705 | GEO
Project description:Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms play an important role in the initiation and progression of colon cancer. Curcumin is a dietary cancer preventive phytochemical with promising effect in suppressing colitis-associated colon cancer (CAC) in azoxymethane (AOM) and dextran sulfate sodium (DSS) mouse model. In the present study, we confirmed the effect of curcumin in suppressing colon cancer. Using Agilent SureSelect Methyl-seq and RNA-seq, we obtained single-base methylation profile and transcriptome analyses of epithelial cells from control group, AOM and DSS induced group (AOM+DSS), and AOM and DSS induced plus curcumin treated group (AOM+DSS+Curcumin) in a 18 weeks long-term colon cancer mouse model. The average DNA methylation levels of the three groups are significantly different also. Based on differential methylation patterns of three groups, several pathways of genes were identified including IL-8 signaling, LPS-stimulated MAPK signaling and colorectal cancer metastasis signaling. Among these methylated pathways and genes, Tnf, an inflammatory gene stood out with decreased DNA CpG methylation in the AOM-DSS as compared to the control group and interestingly curcumin reversed the CpG methylation (validated by pyrosequencing). The functional role of DNA methylation of Tnf was confirmed by in vitro luciferase transcriptional activity assay. In addition, we found that a group of genes associated with the inflammatory responses and their methylation level was decreased in AOM+DSS group but restored in the curcumin treated group. Taken together, in this study, aberrant DNA CpG methylation of the inflammatory response was found in colitis-associated colon cancer and curcumin restored their CpG methlyation, which could potentially explain the inflammatory and cancer protective effects of curcumin. (Note this GEO/dataset is the DNA methyl-seq part of the study.)
2018-06-11 | GSE102645 | GEO
Project description:Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms play an important role in the initiation and progression of colon cancer. Curcumin is a dietary cancer preventive phytochemical with promising effect in suppressing colitis-associated colon cancer (CAC) in azoxymethane (AOM) and dextran sulfate sodium (DSS) mouse model. In the present study, we confirmed the effect of curcumin in suppressing colon cancer. Using Agilent SureSelect Methyl-seq and RNA-seq, we obtained single-base methylation profile and transcriptome analyses of epithelial cells from control group, AOM and DSS induced group (AOM+DSS), and AOM and DSS induced plus curcumin treated group (AOM+DSS+Curcumin) in a 18 weeks long-term colon cancer mouse model. We observed differentially expressed genes in pair-wise comparison and identified several pathways of small set of genes involved in the potential preventive effect of curcumin. These pathways include LPS/IL-1 mediated inhibition of RXR function, NRF2-mediated oxidative stress response, aldosterone signaling in epithelial cells, production of NO and ROS in macrophages, and IL-6 signaling. The average DNA methylation levels of the three groups are significantly different also. Based on differential methylation patterns of three groups, several pathways of genes were identified including IL-8 signaling, LPS-stimulated MAPK signaling and colorectal cancer metastasis signaling. Among these methylated pathways and genes, Tnf, an inflammatory gene stood out with decreased DNA CpG methylation in the AOM-DSS as compared to the control group and interestingly curcumin reversed the CpG methylation (validated by pyrosequencing). These observations correlated with decreased, and increased with curcumin, Tnf expression in RNA-seq (validated by qPCR), respectively. The functional role of DNA methylation of Tnf was confirmed by in vitro luciferase transcriptional activity assay. In addition, we found that a group of genes associated with the inflammatory responses and their methylation level was decreased in AOM+DSS group but restored in the curcumin treated group. Taken together, in this study, aberrant DNA CpG methylation of the inflammatory response was found in colitis-associated colon cancer and curcumin restored their CpG methlyation, which could potentially explain the inflammatory and cancer protective effects of curcumin. (Note this GEO/dataset is the RNA-seq part of the study.)
2018-06-11 | GSE102342 | GEO