Mucosal expression profiling in (un)inflamed colon of patients with ulcerative colitis (UC)
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE48959 | GEO | 2015/01/01
SECONDARY ACCESSION(S): PRJNA212397
REPOSITORIES: GEO
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Project description:In this study, we investigated if miRNA expression in UC mucosa is altered and correlated our findings with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their predicted target mRNA.
2015-01-01 | GSE48958 | GEO
Project description:In this study, we investigated if miRNA expression in UC mucosa is altered and correlated our findings with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their predicted target mRNA.
2015-01-01 | GSE48957 | GEO
Project description:BackgroundUlcerative colitis (UC) is associated with differential colonic expression of genes involved in immune response (e.g. IL8) and barrier integrity (e.g. cadherins). MicroRNAs (miRNAs) are regulators of gene expression and are involved in various immune-related diseases. In this study, we investigated (1) if miRNA expression in UC mucosa is altered and (2) if any of these changes correlate with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their target mRNA.MethodologyColonic mucosal biopsies were obtained from 17 UC (10 active and 7 inactive) patients and 10 normal controls. Total RNA was used to analyze miRNA and mRNA expression via Affymetrix miRNA 2.0 and Affymetrix Human Gene 1.0ST arrays, respectively. Both miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their corresponding predicted target mRNA. Microarray data were validated with qRT-PCR. Regulation of IL8 and CDH11 expression by hsa-miR-200c-3p was determined by luciferase reporter assays.ResultsWhen comparing active UC patients vs. controls, 51 miRNAs and 1543 gene probe sets gave significantly different signals. In contrast, in inactive UC vs. controls, no significant miRNA expression differences were found while 155 gene probe sets had significantly different signals. We then identified potential target genes of the significantly dysregulated miRNAs and genes in active UC vs. controls and found a highly significant inverse correlation between hsa-miR-200c-3p and IL8, an inflammatory marker, and between hsa-miR-200c-3p and CDH11, a gene related to intestinal epithelial barrier function. We could demonstrate that hsa-miR-200c-3p directly regulates IL8 and CDH11 expression.ConclusionDifferential expression of immune- and barrier-related genes in inflamed UC mucosa may be influenced by altered expression of miRNAs. Integrated analysis of miRNA and mRNA expression profiles revealed hsa-miR-200c-3p for use of miRNA mimics as therapeutics.
| S-EPMC4278881 | biostudies-literature
Project description:BACKGROUND: Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. METHODS: Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. RESULTS: A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). CONCLUSIONS: A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC.
| S-EPMC3441502 | biostudies-literature
Project description:Ulcerative colitis (UC) arises from a complex interplay between host and environmental factors, but with a largely unsolved pathophysiology. The pathophysiology was outlined by RNA-sequencing of mucosal biopsies from non-inflamed and inflamed colon of UC patients (14 and 17, respectively), and from 27 patients without intestinal inflammation. Genes differentially expressed (DE), or present in enriched gene sets, were investigated using statistical text analysis of functional protein information. Compared with controls, inflamed and non-inflamed UC mucosa displayed 9360 and 52 DE genes, respectively. Seventy-three non-pseudogenes were DE relative to both gender and inflammation. Mitochondrial processes were downregulated in inflamed and upregulated in non-inflamed UC mucosa, whereas angiogenesis and endoplasmic reticulum (ER) stress were upregulated in both tissue states. Immune responses were upregulated in inflamed mucosa, whereas the non-inflamed UC mucosa presented both up- and downregulated gene sets. DE and enriched genes overlapped with genes present in inflammatory bowel disease genome-wide associated loci (p = 1.43 × 10-18), especially regarding immune responses, respiratory chain, angiogenesis, ER stress, and steroid hormone metabolism. Apart from confirming established pathophysiological mechanisms of immune cells, our study provides evidence for involvement of less described pathways (e.g., respiratory chain, ER stress, fatty-acid oxidation, steroid hormone metabolism and angiogenesis).
| S-EPMC9266769 | biostudies-literature
Project description:The greatest obstacle to an HIV cure is the persistence of latently infected cellular reservoirs in people living with HIV (PLWH) taking antiretroviral therapy (ART). However, no consensus exists on the direct link between local tissue inflammation and the HIV burden. Herein, we have compared the levels of local inflammation, epithelial integrity and HIV DNA between inflamed and non-inflamed colon tissue in a PLWH who underwent a colectomy due to ulcerative colitis. We have observed a 27-fold higher frequency of cells harboring HIV DNA in inflamed compared to non-inflamed colon tissue. Analysis of the expression of occludin-1 and claudin-3 confirmed our macroscopic characterization of inflamed and non-inflamed colon. Our results confirm that increased gut permeability and inflammation are associated with a higher frequency of infected cells and suggest that restoring gut barrier integrity may be used as a strategy to reduce inflammation and HIV persistence in the gut.
| S-EPMC7906891 | biostudies-literature
Project description:IBS: Patients who have undergone a diagnostic program for gastrointestinal symptoms and where the diagnosis irritable bowel syndrome was reached. UC: Patients with well-diagnosed ulcerative colitis Keywords: other
2005-04-01 | GSE2461 | GEO
Project description:Microarrays were used to investigate the the effect of vedolizumab (VDZ) therapy on colonic mucosal gene expression in UC patients and compared the changes to those observed with infliximab (IFX) therapy.
2016-10-11 | GSE73661 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-12-01 | GSE87473 | GEO
Project description:To investigate the miRNA expression in colonic mucosal biopsies from endoscopically inflamed and non inflamed regions of ulcerative colitis (UC) patients.Colonic mucosal pinch biopsies were analyzed from the inflamed and non inflamed regions of same UC patient. Total RNA was isolated and differential miRNA profiling was done using microarray platform. Quantitative Real Time PCR was performed in colonic biopsies from inflamed (n = 8) and non-inflamed (n = 8) regions of UC and controls (n = 8) to validate the differential expression of miRNA. Potential targets of dysregulated miRNA were identified by using in silico prediction tools and probable role of these miRNA in inflammatory pathways were predicted.The miRNA profile of inflamed colonic mucosa differs significantly from the non-inflamed. Real time PCR analysis showed that some of the miRNA were differentially expressed in the inflamed mucosa as compared to non inflamed mucosa and controls (miR-125b, miR-223, miR-138, and miR-155), while (miR-200a) did not show any significant changes. In contrast to microarray, where miR-378d showed downregulation in the inflamed mucosa, qRT-PCR showed a significant upregulation in the inflamed mucosa as compared to the non inflamed. The in silico prediction analysis revealed that the genes targeted by these miRNAs play role in the major signaling pathways like MAPK pathway, NF-κB signaling pathway, cell adhesion molecules which are all assciated with UC.The present study reports disease specific alteration in the expression of miR-125b, miR-155, miR-223 and miR-138 in UC patients and also predict their biological significance.
| S-EPMC5550781 | biostudies-other