Project description:Differential gene expression assessed in siTNF-OMe-P treated animals showed significant correlation between improved colon integrity and clinical parameters of colitis with reduced TLR activation, tissue regeneration and reduced pro-inflammatory cytokines, as compared to all treatment groups. This data shows the changes in gene expression profile associated with effective silencing of TNFa by a chemically-modified siRNA in the colon of colitic mice. We performed genome-wide gene expression profiling of 5% DSS-treated mice after intrarectal administration of a)siRNA against TNFa (siTNF), b)siRNA against TNFa modified with O-Methyl nucleotides (siTNF-OMe), c)siRNA against TNFa modified with O-Methyl-propanediol nucleotides (siTNF-OMe-P) and d) siControl (scrambled siRNA).
Project description:Expression profile of colon mucosa of F344 rats treated with 5% DSS during five days vs colon mucosa of F344 rats pre-treated for 20 days with resveratrol 1mg/kg/day and during the five days of 5% DSS administration Keywords: Inflammation experiment Two conditions experiment, colon mucosa of F344 rats treated 5% DSS for 5d vs colon mucosa of F344 rats pretreated with 1mg/kg/day resv + 5% DSS for 5d. 8 Biological samples for each group
Project description:In humans with UC, low-grade dysplasia also develops predominantly in the distal colon, progresses more rapidly to neoplasia than proximal colon low-grade dysplasia and associates with worse patient prognosis. In a mouse model of colitis-associated carcinogenesis induced by administration of the mutagen AOM and the luminal toxin DSS, tumors also develop exclusively in the distal part of the large intestine. We monitored global changes in the transcriptome of mouse proximal and distal colon during exposure to AOM/DSS with the aim to define biological pathways and processes that characterize regional responses of the large intestine to colitis-associated carcinogenesis.
Project description:Expression profile of colon mucosa of F344 rats treated with 5% DSS during five days vs colon mucosa of F344 rats pre-treated for 20 days with resveratrol 1mg/kg/day and during the five days of 5% DSS administration Keywords: Inflammation experiment
Project description:Adamts12-deficient mice undergo more severe colitis than WT mice after induction with DSS. We used microarrays to determine the gene expression differences between Adamts12-deficient and WT mice during ulcerative colitis induced with DSS (dextran sodium sulfate) Fragments of distal colon from DSS-treated (2% DSS during 7 days and 1 day of recovery) and untreated Adamts12-deficient and WT mice were obtained for RNA extraction and hybridiztion with Affymetrix microarrays
Project description:Oral administration of dextran sulfate sodium (DSS) to mice induces ulceration and inflammation in the colons of mice. These changes are somewhat similar to those seen in human inflammatory bowel disease. Here we provide a full transcriptome (RNA-Seq) analysis of different gastrointestinal tissues in the regions affected by the DSS chemical, at different timepoints during the injury-inflammation-recovery cycle. The profiled regions include the distal colon (rectum), where the histological changes are most pronounced, the mid-colon, the anus, which is relatively resistant to damage, and the squamous neo-epithelium of the colon, a skin-like tissue that is found in the colon and is believed to be associated with wound healing. We find that administration of DSS is associated with upregulation of cytokines and inflammatory markers. Moreover, stem cell markers of the homeostatic colonic epithelium are depleted, consistent with reprogramming of epithelia to adopt a wound-healing phenotype. Thus, this dataset faithfully recovers broad changes in gene expression in a mouse model of inflammatory bowel disease-like damage.
Project description:To investigate the effect of transcriptomic changes in colorectal cancer, we performed 3' bulk mRNA sequencing of naive and AOM/DSS treated mice. Mice were subjected to the AOM/DSS mouse model for colorectal cancer or kept under naive conditions. Samples of the most distal 0.5 cm of the colon were taken on day 70 of the model and processed for 3' bulk mRNA sequencing.
Project description:Differential gene expression assessed in siTNF-OMe-P treated animals showed significant correlation between improved colon integrity and clinical parameters of colitis with reduced TLR activation, tissue regeneration and reduced pro-inflammatory cytokines, as compared to all treatment groups. This data shows the changes in gene expression profile associated with effective silencing of TNFa by a chemically-modified siRNA in the colon of colitic mice.
Project description:Purpose: A super carbonate apatite (sCA) nanoparticle is an in vivo pH-sensitive delivery system for siRNA and microRNA. These carriers accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Systemic administration of sCA incorporating siRNA and microRNA has demonstrated superb tumor suppressive effects in vivo. We recently observed that sCA could deliver abundant nucleic acids to the inflammatory sites in rheumatoid arthritis mouse model. Based on the success, we tried to examine whether sCA could deliver sufficient amounts of miRNA into the colorectum inflamed by dextran sodium sulfate (DSS) treatment. Methods: We performed a RNA sequencing analysis of the DSS-treated colon walls. DSS was administered for 4 days and sCA-miR-29a, sCA-miR-29b, sCA-NC-miR was injected on days 1, 2, 3. On day 4, colorectum was removed and the mRNA samples were subject to the RNA sequencing analysis. Results: RNA sequencing of the rectum samples showed a number of enhanced or reduced gene expression in DSS treated NC-miR group on day 4 compared to normal mice. Such tendency of upregulation or downregulation was also noted in DSS-treated NC-miR group on day 2. Comparison of DSS treated samples on day 4 among NC-miR, miR-29a and miR-29b groups, revealed that several gene expression related to the interferon pathway was reversed by miR-29a or miR-29b towards the normal controls. These include Stat1, Stat2, IRF7, IRF9, and IFIT1. Conclusions: Many molecules in the interferon signaling pathway were activated in DSS-induced colitis on day 4 and Stat1, Stat2, IRF7, IRF9, and IFIT1 were key molecules in the interferon related pathways. These findings suggest that sCA-miR-29a or sCA-miR-29b may inhibit type 1 IFN and type 2 IFN pathways which are otherwise activated by DSS treatment.
