Dataset Information

A proteome analysis by LC-MS/MS of human colon mucosal biopsies from gastrointestinal healthy rheumatoid arthritis patients

ABSTRACT: The joint disease rheumatoid arthritis (RA) is characterized by persistent synovitis, leading to cartilage damage, bone erosion, and ultimately impaired joint function. The disease affects 0.5 to 1.0% of adults in developed countries, and is three times more frequent in women than in men. A number of autoantibodies can be detected in RA patient’s serum targeting the patient’s own proteins. Several of these proteins, including rheumatoid factor, can also be detected in patients suffering from other autoimmune diseases, including the inflammatory bowel diseases (IBD). IBD and RA share several genetic risk logi, an altered gut microbiota, and environmental risk factors. Articular involvement is the most common extra-intestinal manifestation in patients diagnosed with IBD, with a prevalence between 17 to 39%. Additionally, methotrexate (MTX) is the most frequently prescribed immunosuppressive drug for RA and the second most for the IBD, indicating close similarities between the two diseases. We, therefore, characterized the protein content (the proteome) of the colon mucosa of gastrointestinal healthy RA patients, to investigate if we could detect IBD-related changes. The LC-MS/MS analysis was conducted as part of a previous study (ProteomeXChange submission PXD001608), enabling a comparison between the two datasets, containing the colon mucosal proteome of 11 RA patients, 10 IBD (ulcerative colitis) patients, and 10 controls. This data submission covers the triplicate proteome analysis of the colon mucosa of 11 gastrointestinal healthy RA patients.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colonic Mucosa, Colon Sigmoideum

DISEASE(S): Rheumatoid Arthritis

SUBMITTER: Tue Bjerg Bennike

LAB HEAD: Allan Stensballe

PROVIDER: PXD003082 | Pride | 2016-09-26

REPOSITORIES: Pride

ACCESS DATA

Publications

Proteome Analysis of Rheumatoid Arthritis Gut Mucosa.

Bennike Tue Bjerg TB Ellingsen Torkell T Glerup Henning H Bonderup Ole Kristian OK Carlsen Thomas Gelsing TG Meyer Michael Kruse MK Bøgsted Martin M Christiansen Gunna G Birkelund Svend S Andersen Vibeke V Stensballe Allan A

Journal of proteome research 20160927 1

Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly ...[more]

PMID: 27627584

Similar Datasets

Project description:Background and aims: Mucosal abnormalities are potentially important in the primary pathogenesis of ulcerative colitis (UC). We investigated the mucosal transcriptomic expression profiles of biopsies from patients with UC and healthy controls (HC), taken from macroscopically non-inflamed tissue from the terminal ileum and three colonic locations with the objective of identifying abnormal molecules that might be involved in disease development. Methods: Whole-genome transcriptional analysis was performed on intestinal biopsies taken from 24 UC, 26 HC and 14 patients with CrohnM-bM-^@M-^Ys disease. Differential gene expression analysis was performed at each tissue location separately and results were then meta-analysed using FisherM-bM-^@M-^Ys method. Significantly differentially expressed genes were validated using qPCR. Gene location within the colon was determined using immunohistochemistry, subcellular fractionation, electron and confocal microscopy. DNA methylation was quantified by pyrosequencing. Results: Seven probes were abnormally expressed throughout the colon in UC patients with Family with sequence similarity member 5 C (FAM5C) being the most significantly underexpressed. Attenuated expression of FAM5C in UC was independent of inflammation, unrelated to phenotype or treatment, and remained low at rebiopsy approximately 23 months later. FAM5C is localised to the brush border of the colonic epithelium and expression is influenced by DNA methylation within its promoter. Conclusion: Genome-wide expression analysis of non-inflamed mucosal biopsies from UC patients identified FAM5C as significantly under-expressed throughout the colon in a major sub-set of patients with UC. Low levels of this gene could predispose to or contribute to the maintenance of the characteristic mucosal inflammation seen in this condition. Total RNA was extracted from the intestinal biopsies taken from macroscopically normal mucosa in the rectum, descending colon, ascending colon and terminal ileum in clinically quiescent Ulcerative colitis and Crohn's disease patients and compared to healthy controls. Normalized data for 26,261 probes out of 47,323 only. Criteria for inclusion not specified. The non-normalized matrix contains the complete non-normalized data for all probes.

Project description:Study 1: Transcriptomic profiles in colon tissue from inflammatory bowel diseases patients in relation to N-nitroso compound exposure and colorectal cancer risk Study 1: N-nitroso compounds (NOC) have been suggested to play a role in human cancer development but definitive evidence is still lacking. In this study we investigated gene expression modifications induced in human colon tissue in relation to NOC exposure to gain insight in the relevance of these compounds in human colorectal cancer (CRC) development. Since there are indications that inflammation stimulates endogenous NOC formation, the study population consisted of patients with inflammatory bowel disease (IBD) and irritable bowel syndrome patients as controls without inflammation. Strong transcriptomic differences were identified in colonic biopsies from IBD patients and compared to controls that enhance the understanding of IBD pathophysiology. However, fecal NOC levels were not increased in IBD patients, suggesting that inflammation did not stimulate NOC formation. By relating gene expression changes of all subjects to fecal NOC levels, we did, however, identify a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending the molecular basis of NOC-induced carcinogenesis. We conclude that NOC exposure is associated with gene expression modifications in the colon that may increase CRC risk in humans. Study 2: Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon Study 2: Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat intake on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to transcriptomic changes induced in colonic tissue. In order to evaluate the potential effect of an inflamed colon on endogenous nitrosation, the study population consisted of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) control subjects without inflammation. The intervention had no effect on fecal NOC formation but fecal water genotoxicity significantly increased in response to red meat intake. Since IBD patients showed no difference in fecal NOC formation or fecal water genotoxicity levels as compared to IBS controls, for transcriptomic analyses, all subjects were grouped together. Genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated that are known to play a part in the carcinogenic process in the human colon. These results are in line with a possible oxidative effect of dietary heme. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a possible risk of CRC development in humans. The study investigated transcription levels in human colon biopsies obtained during a colonoscopic exam in 32 subjects suffering from either inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS). IBS patients served as control patients for comparison with IBD patients (see Study 1). 12 of these patients (6 IBD and 6 IBS) also followed a 7-day diet high in red meat (300 grams/day) after which a second colonscopic exam was performed to obtain colon biopsies to investigate the effect of the red meat intervention (Study 2). For each subject, cRNA copies of mRNA isolated from the colon biopsies were labeled with one dye (Cy3) and each sample was hybridized on a separate array. One replicate per subject or before/after red meat intervention (so 44 arrays in total, i.e. 20 before patients and 12 before and after patients).

Dataset Information

A proteome analysis by LC-MS/MS of human colon mucosal biopsies from gastrointestinal healthy rheumatoid arthritis patients

Publications

Proteome Analysis of Rheumatoid Arthritis Gut Mucosa.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure