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dc.contributor.advisorTerkel, Hansen
dc.contributor.authorSchniers, Armin
dc.date.accessioned2019-07-29T11:14:36Z
dc.date.available2019-07-29T11:14:36Z
dc.date.embargoEndDate2021-06-18
dc.date.issued2019-06-18
dc.description.abstractThis 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.en_US
dc.description.doctoraltypeph.d.en_US
dc.description.popularabstractThis work elucidates the properties of human colon mucosa in ulcerative colitis (UC) on the protein level. UC is a chronic inflammatory disease that affects colon and rectum. UC patients suffer from symptoms such as bloody diarrhea and abdominal pain. We compared abundances of more than 8,000 proteins between patients with active ulcerative colitis, patients in remission from UC, and healthy controls. We observe distinct functional differences between these states. The remission state presents with protein abundance characteristics of both active UC and healthy controls. Differences to healthy controls that persist in remission may contribute to relapses and symptoms that occur in this state. Our findings improve the understanding of UC and suggest new potential treatment approaches. We furthermore present a model to predict the disease progression, which could bring great benefit for clinical decision-making.en_US
dc.description.sponsorshipThis work was funded by Helse Nord RHF and UiT The Arctic University of Norway.en_US
dc.identifier.urihttps://hdl.handle.net/10037/15810
dc.language.isoengen_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.relation.haspart<p>Paper I: Schniers, A., Anderssen, E., Fenton, C.G., Goll, R., Pasing, Y., Paulssen, R.H., Florholmen, J. & Hansen, T. (2017). The Proteome of Ulcerative Colitis in Colon Biopsies from Adults ‐ Optimized Sample Preparation and Comparison with Healthy Controls. <i>Proteomics Clinical Applications, 11</i>(11-12), 1700053. Also available at <a href=https://doi.org/10.1002/prca.201700053> https://doi.org/10.1002/prca.201700053</a>. <p>Paper II: Schniers, A., Goll, R., Pasing, Y., Sørbye, S.W., Florholmen, J. & Hansen, T. (2019). Ulcerative colitis: functional analysis of the in-depth proteome. <i>Clinical Proteomics, 16</i>, 4. Also available in Munin at <a href=https://hdl.handle.net/10037/15619>https://hdl.handle.net/10037/15619</a>. <p>Paper III: Schniers, A., Goll, R., Sørbye, S.W., Florholmen, J. & Hansen, T. The proteome of ulcerative colitis in remission – functional differences in comparison with healthy controls and the active disease. (Manuscript). Available in the file “thesis_entire.pdf”. <p>Paper IV: Schniers, A., Goll, R., Sørbye, S.W., Stenlund, H., Florholmen, J. & Hansen, T. Prediction of the 1-year outcome for Ulcerative Colitis from the proteomic profile of treatment naïve patients. (Manuscript). Available in the file “thesis_entire.pdf”.en_US
dc.rights.accessRightsembargoedAccessen_US
dc.subject.courseIDDOKTOR-003
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical molecular biology: 711en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711en_US
dc.titleThe proteome of ulcerative colitis - Functional analyses of the active disease and the remission state in comparison with healthy controlsen_US
dc.typeDoctoral thesisen_US
dc.typeDoktorgradsavhandlingen_US


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