The proteome of ulcerative colitis - Functional analyses of the active disease and the remission state in comparison with healthy controls

This work characterizes the proteome of human colon mucosa in ulcerative colitis (UC). We developed an optimized sample preparation method of colon mucosa biopsies for bottom-up proteomics and applied it to characterize the proteomes of active UC, remission from UC, and healthy controls. Abundances of proteins related to the immune system and to protein processing in the endoplasmic reticulum are increased in active UC compared to healthy controls. Lower abundant are metallothioneins, fibrillary collagens, bile acid transport proteins, carbonic anhydrases, and proteins related to nutrient, energy, and xenobiotic metabolism. In general, the remission state seems to be a blend of healthy and diseased state. We characterized the remission state based on the proteins that were significantly different abundant in remission compared to active UC and/or healthy controls. A small fraction of these proteins (associated functions: hormones, vitamins, lipoproteins, muscle) is higher abundant in remission than in both active UC and healthy controls. Most proteins (associated functions: immune system, protein processing, collagen) show similar abundances in remission as in healthy controls. About one fourth of the remission abundances (associated functions: nutrient and energy metabolism, PPAR signaling) was between those in active UC and healthy controls and significantly different from both. Approximately one eighth of the proteins was at similar levels as in active UC (associated functions: immunoglobulins, metallothioneins, prostaglandin metabolism). Protein abundances that are not at equal levels as in healthy controls may contribute to relapses and symptoms in remission. Our findings have clinical implications. Several functions apart from the inflammation could be readily addressable with medication. The abundances of the routinely used biomarkers calprotectin and lactotransferrin are representative for only a small minority of differently abundant proteins. An additional assessment of more representative proteins may be useful. We furthermore present a model for the prediction of the 1-year-outcome that could bring benefit for clinical decision-making

Ulcerative colitis: functional analysis of the in-depth proteome

Abstract Background Ulcerative colitis (UC) is one major form of inflammatory bowel disease. The cause and the pathophysiology of the disease are not fully understood and we therefor aim in this study to identify important pathophysiological features in UC from proteomics data. Methods Colon mucosa biopsies from inflamed tissue of untreated UC patients at diagnosis and from healthy controls were obtained during colonoscopy. Quantitative protein data was acquired by bottom-up proteomics and furthermore processed with MaxQuant. The quantitative proteome data was analyzed with Perseus and enrichment data was analyzed by ClueGO for Cytoscape. Results The generated proteome dataset is to-date the deepest from colon mucosa biopsies with 8562 identified proteins whereof 6818 were quantified in > 70% of the samples. We report abundance differences between UC and healthy controls and the respective p values for all quantified proteins in the supporting information. From this data set enrichment analysis revealed decreased protein abundances in UC for metallothioneins, PPAR-inducible proteins, fibrillar collagens and proteins involved in bile acid transport as well as metabolic functions of nutrients, energy, steroids, xenobiotics and carbonate. On the other hand increased abundances were enriched in immune response and protein processing in the endoplasmic reticulum, e.g. unfolded protein response and signal peptidase complex proteins. Conclusions This explorative study describes the most affected functions in UC tissue. Our results complemented previous findings substantially. Decreased abundances of signal peptidase complex proteins in UC are a new discovery

3-(1<em>H</em>-Indol-3-yl)-4-(morpholin-4-yl)cyclobut-3-ene-1,2-dione

3-(1<em>H</em>-Indol-3-yl)-4-(morpholin-4-yl)cyclobut-3-ene-1,2-dione was obtained in good yields (72–82%) by nucleophilic substitution of 3-chloro-4-(1<em>H</em>-indol-3-yl)cyclobut-3-ene-1,2-dione with morpholine