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| Proteomic studies in IBD | References | Analytical technique(s) | Type of study (cell line, animal, human) | Significant finding(s) |
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| Biofluid proteomics | Meuwis et al. 2007 [50] | SELDI-TOF-MS | Human | Identification of PF4, MRP8, FIBA, and Hpa2 as potential biomarkers of disease activity in IBD |
| Meuwis et al. 2008 [61] | SELDI-TOF-MS | Human | Positive correlation between PF4 level and nonresponse to infliximab therapy in CD |
| Kanmura et al. 2009 [62] | Protein array technology coupling ProteinChip system with SELDI-TOF/MS | Human | Identification of 3 increased in abundance proteins (HNP 1–3) in the serum of active UC patients as new biomarkers of UC disease activity |
| Hatsugai et al. 2010 [71] | 2DE, discriminant analysis (OPLS-DA), and MALDI-TOF MS/MS | Human | Identification of a panel of proteins that could discriminate between UC and CD including ANXA6, PRDX2, ABHD14B, cyclophilin A, CA2, ACTB, and S100A9 |
| Gazouli et al. 2013 [72] | 2DE and MALDI-TOF-MS | Human | Identification of a panel of increased in abundance proteins in the primary infliximab nonresponsive patients including: APOA1, APOE, CO4B, PLMN, TRFE, APOH, and CLUS in comparison to infliximab-induced remission patients |
| Vaiopoulou et al. 2015 [63] | 2DE and MALDI-TOF-MS | Human | Overexpression of ceruloplasmin and apolipoprotein B-100 (APOB) in children and clusterin in adults with CD |
| Viennois et al. 2015 [76] | 2DE and MALDI-TOF/TOF MS | Murine | Identification of altered expression of proteins specific to intestinal inflammation development (PZP, COL1A1, and PRDX2), IL10−/− murine model inflammation (PZP, PRDX2), arthritic inflammation development (serum amyloid P-component and transthyretin), and nonspecific inflammation (HP, ITIH4, HPX, C3, and A1BG) |
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| Tissue proteomics | Barcelo-Batllori et al. 2002 [131] | 2DE and MALDI-TOF-MS | Cell line and human | Increase of indoleamine-2,3-dioxygenase in the purified IEC from IBD patients relative to normal controls |
| Hsieh et al. 2006 [99] | 2DE and MALDI-TOF-MS | Human | Identification of 19 altered proteins expression (13 decreased in abundance and 6 increased in abundance) in the active compartment of UC mucosa relative to control. Altered regulation of mitochondrial proteins raising the possibility of mitochondrial dysfunction in UC |
| Liu et al. 2007 [137] | 2DE, MALDI-TOF-MS, and real-time RT-PCR | Murine | Alteration of a series of apoptosis-related proteins (increased in abundance IL-12 p40 and decreased in abundance CARD, PYD domain-containing protein, and proteasome activator complex subunit 2), proteins involved in cell growth, differentiation, and signal transduction (increased in abundance NDPKs and E2N), infl ammatory factors (increased in abundance MRP14), and metabolism/oxidative stress response-related proteins (increased in abundance ATP-citrate synthase, phosphoglycerate mutase, and dismutase) in lymphocytes from a rat colitis model |
| Shkoda et al. 2007 [81] | 2DE and MALDI-TOF MS | Human | Identification of several differentially expressed proteins in the IEC from active IBD patients relative to controls (including L-lactate dehydrogenase, NADPH prostaglandin E2 reductase, keratin 19, and Rho GDI α) |
| Fogt et al. 2008 [92] | 2DE and LC-MS/MS | Human | Identification of increased expression of proteins that are mainly involved in inflammation and repair (proto-cadherins, α-1 antitrypsin, tetratricopeptide repeat domains, caldesmon, and mutant desmin) in the active UC tissue relative to the inactive proximal mucosa |
| Brentnall et al. 2009 [121] | HPLC, Q-TOF MS/MS, and iTRAQ labelling | Human | Identification of differential protein expression relating to mitochondria (CPS1 and S100P) associated with UC neoplastic progression |
| Araki et al. 2009 [129] | 2DE and LC-MS/MS | Cell line and human | Identification of overexpression of HSP47 in UC-associated cancer relative to sporadic colon cancer tissues |
| May et al. 2011 [126] | Label-free LTQ-Orbitrap hybrid MS coupled with HPLC | Human | Identification of two differentially expressed mitochondrial proteins (TRAP1, CPS1) associated with UC neoplastic progression, which was found in both dysplastic and nondysplastic tissues |
| Zhao et al. 2011 [117] | 2DE and MALDI TOF/TOF MS | Human | Detecting P-p38 increase and MAWBP/galectin-3 decrease in active UC compared to normal controls; proposing P38 MAPK pathway involvement in UC disease activity |
| M’Koma et al. 2011 [78] | Histology-directed MALDI-MS(tissue imaging) | Human | Discriminatory colonic submucosa proteomic profile between UC and Crohn’s colitis via investigation of MS spectral peaks |
| Poulsen et al. 2012 [102] | 2DE and MALDI-TOF MS together with PCA analysis | Human | Identification of 33 individual proteins with altered expression in the active UC mucosa relative to proximal inactive mucosa 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) |
| Kwon et al. 2012 [115] | 2DE and MALDI-TOF/TOF MS | Human | Identification of 3 proteins with altered expression in UC and tuberculous colitis (TC) (mutant β-actin, α-enolase, Charcot-Leyden crystal) relative to control, suggesting α-enolase as a candidate biomarker for differential diagnosis of TC and UC |
| Barnett et al. 2013 [149] | 2DE and LC-MS | Murine | Reduced abundance of proteins associated with immune and inflammatory response as well as fibrinogenesis pathways, and increased abundance of those associated with xenobiotic metabolism pathways in response to GrTP |
| Seeley et al. 2013 [80] | Histology-directed MALDI-MS(tissue imaging) | Human | Identification of a support vector machine algorithm consisting of 25 peaks able to differentiate spectra from CC and UC with 76.9% spectral accuracy |
| Han et al. 2013 [104] | Label-free LC-MS | Human | Suggestion of 3 proteins as potential biomarkers for active CD, including PRG2, LCP1, and PSME1 |
| Zhou et al. 2013 [128] | 2DE, WB, and MALDI MS | Human | Identified 6 differentially expressed proteins (prohibitin, calreticulin, apolipoprotein A-I, intelectin-1, protein disulphide isomerase, and glutathione s-transferase Pi) in active CD mucosa relative to the adjacent normal-looking mucosa |
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| | Bennike et al. 2015 [113] | Label-free (LFQ) proteomic analysis | Human | Comparing UC to normal biopsies identified proteins with statistically significant altered abundance in the UC biopsies to be from neutrophils and associated with the formation of neutrophil extracellular traps (NETs) suggesting stimulation of innate immunity. |
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| Organelle proteomics | O’Morain et al. 1985 [161] | 2DE and MS | Human | Identification of specific alterations in the principal subcellular organelles, especially the plasma membrane, lysosomes, and mitochondria in IBD in comparison to control |
| Nanni et al. 2009 [73] | 1D SDS-PAGE and nano-LC ESI/Q-TOF-MS with targeted MS/MS analysis | Human | Identification of certain decreased in abundance (Annexin A1, malate dehydrogenase) and increased (different histones and ubiquitin in the nuclear fraction; tryptase alpha-1 precursor in the cytosolic fraction; ATP synthase subunit beta and heat shock 70 kDa protein-5 in the fraction containing membranes) proteins in CD patients relative to controls |
| Nanni et al. 2009 [212] | LC ESI/Q-TOF-MS with targeted MS/MS analysis | Human | Suggestion of a specific serum exoprotease activity with proinflammatory properties in CD |
| Corfe et al. 2015 [172] | HPLC, ESI/Q-TOF MS-MS, and iTRAQ labelling | Human | Reduced levels of K8, K18, and K19 and vimentin (VIM) in acute distal UC mucosa compared to controls and noninflamed proximal mucosa; reduced levels of IF–associated proteins in UC with PSC and UC with dysplasia; increased levels of K8, K18, and K19 and VIM in longstanding pancolitis in remission relative to controls and recent-onset colitis in remission |
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| | Denadai-Souza et al. 2018 [167] | MS-based functional proteomic analysis employing activity-based probes | Human | Profiling and identification of active serine proteases were performed to monitor availability of enzyme active sites in colonic tissues from CD or UC patients. Seven serine proteases including cathepsin G, plasma kallikrein, plasmin, tryptase, chymotrypsin-like elastase 3A, thrombin, and aminopeptidase B were identified, of which cathepsin G and thrombin were overactive in IBD patient samples compared to healthy controls. |
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