Expression data from intestinal mucosa of patients with UC
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE38713 | GEO | 2012/11/09
SECONDARY ACCESSION(S): PRJNA168492
REPOSITORIES: GEO
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Project description:Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission. We performed a whole-genome transcriptional analysis of colonic biopsies from patients with histologically active and inactive UC, as well as non-inflammatory controls. Ulcerative colitis patients and non-inflammatory controls were collected for RNA extraction and hybridization on Affymetrix microarrays. Inclusion criteria for UC patients were: age between 18 and 65, diagnosis of UC established at least 6 months before inclusion and exclusion of concomitant infection. Active disease was defined by endoscopic and histologic score: Mayo sub score >=2 and MATTS >=3 respectively . Inactive disease was also defined by endoscopic and histologic score: Mayo sub score =0 and MATTS <=2 respectively, and a remission state for a minimum of 5 month prior to biopsy collection, and remained inactive for at least 6 months after. Uninvolved mucosa from patients with active UC was defined as a colonic segment with completely normal endoscopic appearance, normal histology, and absence of any previous evidence of active disease. Finally, a total of 43 biopsies were analyzed: 13 healthy controls, 8 inactive UC, 7 non-involved active UC and 15 involved active UC.
2012-11-09 | E-GEOD-38713 | biostudies-arrayexpress
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2017-09-11 | GSE94648 | GEO
Project description:Inflammatory bowel diseases (IBDs) including ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory diseases with increasing worldwide prevalence that show a perplexing heterogeneity in manifestations and response to treatment. We applied single cell RNA sequencing (scRNAseq) a to colonic tissue from a combined healthy, UC and CD cohort.
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Project description:Ulcerative colitis (UC), a chronic, nonspecific inflammatory bowel disease characterized by continuous and diffuse inflammatory changes in the colonic mucosa, requires novel treatment method. Photodynamic therapy (PDT), as a promising physico-chemical treatment method, were used to treat UC rats’ model with novel photosensitizer LD4 in this paper, the treatment effect and mechanism was investigated. LD4-PDT could improve the survival rate of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC model rats, decrease expression of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), myeloperoxidase (MPO) and increase the expression of glutathione (GSH) and superoxide oxidase (SOD), while protecting the integrity of the intestinal epithelium. LD4-PDT treatment could rebuild the intestinal microflora composition and reprogram the colonic protein profiles in TNBS-induced rats to almost the normal state. Proteomics analysis based upon TNBS-induced UC model rats revealed that Amine oxidase copper-containing 1 (AOC1) was a potential target of LD4-PDT. Novel photosensitizer agent LD4-PDT represents an efficient treatment method for UC, and AOC1 may be a promising target.
2021-09-24 | PXD027815 | Pride
Project description:Ulcerative colitis is a chronic inflammatory disorder in the lower part of the digestive system. Despite of many functional studies, the hidden mechanisms of this complex disease limit complete remission. Here, we investigated transcriptomic signature of ulcerative colitis using RNA sequencing obtained from 15 active (inflamed), 15 inactive (non-inflamed) samples of ulcerative colitis, and 15 healthy controls. The transcriptomics profiling revealed that inflammatory transcriptomic signature was highly enriched in active samples compared to inactive or healthy control samples. However, this bulk RNAseq cannot provide the cell type information, which play a key role in such a chronic inflammation. To overcome this limitation, we borrowed the power of single cell RNAseq. Deconvolution of bulk RNAseq based on the single cell expression estimated active UC enriched cell types including inflammatory fibroblast and inflammatory monocytes. This integrative approach using bulk and single cell transcriptomics provide not only target genes but also target cell types of ulcerative colitis for therapeutic purpose.
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Project description:Background and Aims: The pathophysiology of the diarrhoea-predominant inflammatory bowel disease collagenous colitis (CC) is poorly described. Our aim was to use RNA sequencing of colonic biopsies from patients with active CC, CC in remission, refractory CC, ulcerative colitis (UC), and controls to gain insight into CC pathophysiology, identify additional genetic signatures linked to CC, and uncover targets for future therapeutic agents. Methods: We performed whole transcriptome sequencing of CC colonic samples from patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory patients, UC and healthy controls (n=9-13). Bulk mucosa and laser-captured microdissected intestinal epithelial cell gene expression was functionally analyzed by gene-set enrichment and gene-set variation analyses to identify statistically significant pathways and cells, respectively, that change in CC. Leading genes and cells were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared CC transcriptome with that from UC samples. Results: We identified an activation of the adaptive immune response to bacteria in active CC compared to that in remission that could be mediated by dendritic cells. However, a unique signature of genes related to the immune response and DNA transcription remain dysregulated after achieving remission. Budesonide-refractory CC patients fail to restore normal gene expression, which results in a transcriptomic profile close to UC. Intestinal epithelial CC cells displayed an impaired cell proliferation and increased antigen presentation. Conclusion: Our study confirmed previous findings from GWAS and immunological studies related to CC pathogenesis and describes novel genes, pathways and cells that might contribute to the pathophysiology of CC, ongoing epithelial damage, and complications associated with CC.
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Project description:The colonic inner mucus layer protects us from pathogen invasion and commensal-induced inflammation. Mucus abnormalities are common in ulcerative colitis (UC), but their cause and importance are unknown. The aim of this study was to determine the role of compositional mucus barrier alterations in UC. In this single-center case-control study, sigmoid colon biopsies were obtained from UC patients with ongoing inflammation (n=36) and in remission (n=28), and from 47 patients without inflammatory bowel disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analyzed by mass spectrometry. Mucus barrier integrity and goblet cell response to microbial challenge were also assessed for a subset of patients. The core colonic mucus proteome was shown to consist of a small set of 29 secreted proteins. Patients with active UC had reduced levels of major structural components, including the mucin MUC2 (p<0.0001), also in mucus from non-inflamed segments, and their goblet cell secretory response to microbial stimulus was abrogated. Functional mucus barrier failure was observed in a subset of UC patients with and without active inflammation, and accompanied by alterations in proteins associated with mucus secretion and luminal organization. This study represents the first characterization and comparison of the mucus proteomes of the inflamed and non-inflamed colon. Core mucus structural components were reduced in active UC, also in mucus from non-inflamed segments. Thus, weakening of the mucus barrier is likely to occur early in UC pathogenesis, and represents a novel target for intervention.
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Project description:The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients. Experiment Overall Design: The series contain eight UC samples with macroscopic signs of inflammation, 13 UC smaples without macroscopic signs of inflammation, five control subjects.
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Project description:Gene expression patterns of Crohn's disease (CD) and ulcerative colitis (UC) colonic specimens were analyzed using whole-genome microarrays. Healthy control samples were included in order to detect gene expression changes associated with CD or UC. CD and UC samples were also compared in order to identify the molecular mechanisms that distinguish both fenotypes of inflammatory bowel disease. Total RNA obtained from intestinal biopsies were analyzed using whole-genome microarrays.
2013-09-23 | E-GEOD-36807 | biostudies-arrayexpress
Project description:Infliximab, an anti-TNF-alpha monoclonal antibody, is an effective treatment for ulcerative colitis (UC) with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-TNF-alpha is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in UC. Keywords: drug response Twenty-four patients with active UC, refractory to corticosteroids and/or immunosuppression, underwent colonoscopy with biopsies from diseased colon within a week prior to the first intravenous infusion of 5 mg infliximab per kg body weight. Response to infliximab was defined as endoscopic and histologic healing at 4-6 weeks after first infliximab treatment. Six control patients with normal colonoscopy were included. Total RNA was isolated from colonic mucosal biopsies, labelled and hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays.
2010-01-06 | E-GEOD-14580 | biostudies-arrayexpress