Digestive Diseases and Sciences

, Volume 62, Issue 9, pp 2266–2276 | Cite as

Proteomics in Inflammatory Bowel Disease: Approach Using Animal Models

  • Fadi H. Mourad
  • Yunki Yau
  • Valerie C. Wasinger
  • Rupert W. Leong
Review

Abstract

Recently, proteomics studies have provided important information on the role of proteins in health and disease. In the domain of inflammatory bowel disease, proteomics has shed important light on the pathogenesis and pathophysiology of inflammation and has contributed to the discovery of some putative clinical biomarkers of disease activity. By being able to obtain a large number of specimens from multiple sites and control for confounding environmental, genetic, and metabolic factors, proteomics studies using animal models of colitis offered an alternative approach to human studies. Our aim is to review the information and lessons acquired so far from the use of proteomics in animal models of colitis. These studies helped understand the importance of different proteins at different stages of the disease and unraveled the different pathways that are activated or inhibited during the inflammatory process. Expressed proteins related to inflammation, cellular structure, endoplasmic reticulum stress, and energy depletion advanced the knowledge about the reaction of intestinal cells to inflammation and repair. The role of mesenteric lymphocytes, exosomes, and the intestinal mucosal barrier was emphasized in the inflammatory process. In addition, studies in animal models revealed mechanisms of the beneficial effects of some therapeutic interventions and foods or food components on intestinal inflammation by monitoring changes in protein expression and paved the way for some new possible inflammatory pathways to target in the future. Advances in proteomics technology will further clarify the interaction between intestinal microbiota and IBD pathogenesis and investigate the gene-environmental axis of IBD etiology.

Keywords

Proteomics Inflammatory bowel disease Biomarkers Animal models of colitis, inflammation 

References

  1. 1.
    Wasinger VC, Cordwell SJ, Cerpa-Poljak A, et al. Progress with gene-product mapping of the mollicutes: Mycoplasma genitalium. Electrophoresis. 1995;16:1090–1094.CrossRefPubMedGoogle Scholar
  2. 2.
    Hoehn GT, Suffredini AF. Proteomics. Crit Care Med. 2005;33:S444–S448.CrossRefPubMedGoogle Scholar
  3. 3.
    Anderson NL, Anderson NG. Proteome and proteomics: new technologies, new concepts, and new words. Electrophoresis. 1998;19:1853–1861.CrossRefPubMedGoogle Scholar
  4. 4.
    Arsene-Ploetze F, Bertin PN, Carapito C. Proteomic tools to decipher microbial community structure and functioning. Environ Sci Pollut Res Int. 2015;22:13599–13612.CrossRefPubMedGoogle Scholar
  5. 5.
    Polytarchou C, Koukos G, Iliopoulos D. Systems biology in inflammatory bowel diseases: ready for prime time. Curr Opin Gastroenterol. 2014;30:339–346.CrossRefPubMedGoogle Scholar
  6. 6.
    Rifai N, Gillette MA, Carr SA. Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol. 2006;24:971–983.CrossRefPubMedGoogle Scholar
  7. 7.
    Hsieh SY, Shih TC, Yeh CY, Lin CJ, Chou YY, Lee YS. Comparative proteomic studies on the pathogenesis of human ulcerative colitis. Proteomics. 2006;6:5322–5331.CrossRefPubMedGoogle Scholar
  8. 8.
    Barcelo-Batllori S, Andre M, Servis C, et al. Proteomic analysis of cytokine induced proteins in human intestinal epithelial cells: implications for inflammatory bowel diseases. Proteomics. 2002;2:551–560.CrossRefPubMedGoogle Scholar
  9. 9.
    Felley-Bosco E, Andre M. Proteomics and chronic inflammatory bowel diseases. Pathol Res Pract. 2004;200:129–133.CrossRefPubMedGoogle Scholar
  10. 10.
    Fogt F, Jian B, Krieg RC, Wellmann A. Proteomic analysis of mucosal preparations from patients with ulcerative colitis. Mol Med Rep. 2008;1:51–54.PubMedGoogle Scholar
  11. 11.
    Shkoda A, Werner T, Daniel H, Gunckel M, Rogler G, Haller D. Differential protein expression profile in the intestinal epithelium from patients with inflammatory bowel disease. J Proteome Res. 2007;6:1114–1125.CrossRefPubMedGoogle Scholar
  12. 12.
    Bennike T, Birkelund S, Stensballe A, Andersen V. Biomarkers in inflammatory bowel diseases: current status and proteomics identification strategies. World J Gastroenterol. 2014;20:3231–3244.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chan PP, Wasinger VC, Leong RW. Current application of proteomics in biomarker discovery for inflammatory bowel disease. World J Gastrointest Pathophysiol. 2016;7:27–37.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Soubieres AA, Poullis A. Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease. World J Gastrointest Pharmacol Ther. 2016;7:41–50.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Buhrke T, Lengler I, Lampen A. Analysis of proteomic changes induced upon cellular differentiation of the human intestinal cell line Caco-2. Dev Growth Differ. 2011;53:411–426.CrossRefPubMedGoogle Scholar
  16. 16.
    Kaulmann A, Serchi T, Renaut J, Hoffmann L, Bohn T. Carotenoid exposure of Caco-2 intestinal epithelial cells did not affect selected inflammatory markers but altered their proteomic response. Br J Nutr. 2012;108:963–973.CrossRefPubMedGoogle Scholar
  17. 17.
    Bertrand J, Tennoune N, Marion-Letellier R, et al. Evaluation of ubiquitinated proteins by proteomics reveals the role of the ubiquitin proteasome system in the regulation of Grp75 and Grp78 chaperone proteins during intestinal inflammation. Proteomics. 2013;13:3284–3292.CrossRefPubMedGoogle Scholar
  18. 18.
    Barnett M, Young W, Cooney J, Roy N. Metabolomics and proteomics, and what to do with all these ‘Omes’: insights from nutrigenomic investigations in New Zealand. J Nutrigenet Nutrigenomics. 2014;7:274–282.CrossRefPubMedGoogle Scholar
  19. 19.
    Sartor RB. Review article: Role of the enteric microflora in the pathogenesis of intestinal inflammation and arthritis. Aliment Pharmacol Ther. 1997;11 Suppl 3:17–22; discussion 22–13.Google Scholar
  20. 20.
    Blumberg RS, Saubermann LJ, Strober W. Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol. 1999;11:648–656.CrossRefPubMedGoogle Scholar
  21. 21.
    Strober W, Fuss IJ, Blumberg RS. The immunology of mucosal models of inflammation. Annu Rev Immunol. 2002;20:495–549.CrossRefPubMedGoogle Scholar
  22. 22.
    Hibi T, Ogata H, Sakuraba A. Animal models of inflammatory bowel disease. J Gastroenterol. 2002;37:409–417.CrossRefPubMedGoogle Scholar
  23. 23.
    Wirtz S, Neurath MF. Animal models of intestinal inflammation: new insights into the molecular pathogenesis and immunotherapy of inflammatory bowel disease. Int J Colorectal Dis. 2000;15:144–160.CrossRefPubMedGoogle Scholar
  24. 24.
    Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75:263–274.CrossRefPubMedGoogle Scholar
  25. 25.
    Panwala CM, Jones JC, Viney JL. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol. 1998;161:5733–5744.PubMedGoogle Scholar
  26. 26.
    Dommels YE, Butts CA, Zhu S, et al. Characterization of intestinal inflammation and identification of related gene expression changes in mdr1a(−/−) mice. Genes Nutr. 2007;2:209–223.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98:694–702.CrossRefPubMedGoogle Scholar
  28. 28.
    Shintani N, Nakajima T, Okamoto T, Kondo T, Nakamura N, Mayumi T. Involvement of CD4+ T cells in the development of dextran sulfate sodium-induced experimental colitis and suppressive effect of IgG on their action. Gen Pharmacol. 1998;31:477–481.CrossRefPubMedGoogle Scholar
  29. 29.
    Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med. 1995;182:1281–1290.CrossRefPubMedGoogle Scholar
  30. 30.
    Viennois E, Baker MT, Xiao B, Wang L, Laroui H, Merlin D. Longitudinal study of circulating protein biomarkers in inflammatory bowel disease. J Proteomics. 2015;112:166–179.CrossRefPubMedGoogle Scholar
  31. 31.
    Piras C, Soggiu A, Greco V, et al. Serum protein profiling of early and advanced stage Crohn’s disease. EuPa Open Proteom. 2014;3:48–59.CrossRefGoogle Scholar
  32. 32.
    Vaiopoulou A, Gazouli M, Papadopoulou A, et al. Serum protein profiling of adults and children with Crohn disease. J Pediatr Gastroenterol Nutr. 2015;60:42–47.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Brignola C, Campieri M, Bazzocchi G, Farruggia P, Tragnone A, Lanfranchi GA. A laboratory index for predicting relapse in asymptomatic patients with Crohn’s disease. Gastroenterology. 1986;91:1490–1494.CrossRefPubMedGoogle Scholar
  34. 34.
    Wasinger VC, Yau Y, Duo X, et al. Low mass blood peptides discriminative of inflammatory bowel disease (IBD) severity: a quantitative proteomic perspective. Mol Cell Proteomics. 2016;15:256–265.CrossRefPubMedGoogle Scholar
  35. 35.
    Shkoda A, Ruiz PA, Daniel H, et al. Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Gastroenterology. 2007;132:190–207.CrossRefPubMedGoogle Scholar
  36. 36.
    Werner T, Shkoda A, Haller D. Intestinal epithelial cell proteome in IL-10 deficient mice and IL-10 receptor reconstituted epithelial cells: impact on chronic inflammation. J Proteome Res. 2007;6:3691–3704.CrossRefPubMedGoogle Scholar
  37. 37.
    Knoch B, Barnett MP, Cooney J, et al. Dietary oleic acid as a control fatty acid for polyunsaturated fatty acid intervention studies: a transcriptomics and proteomics investigation using interleukin-10 gene-deficient mice. Biotechnol J. 2010;5:1226–1240.CrossRefPubMedGoogle Scholar
  38. 38.
    Cooney JM, Barnett MP, Brewster D, et al. Proteomic analysis of colon tissue from interleukin-10 gene-deficient mice fed polyunsaturated Fatty acids with comparison to transcriptomic analysis. J Proteome Res. 2012;11:1065–1077.CrossRefPubMedGoogle Scholar
  39. 39.
    Cooney JM, Barnett MP, Dommels YE, et al. A combined omics approach to evaluate the effects of dietary curcumin on colon inflammation in the Mdr1a(−/−) mouse model of inflammatory bowel disease. J Nutr Biochem. 2016;27:181–192.CrossRefPubMedGoogle Scholar
  40. 40.
    Naito Y, Takagi T, Okada H, et al. Identification of inflammation-related proteins in a murine colitis model by 2D fluorescence difference gel electrophoresis and mass spectrometry. J Gastroenterol Hepatol. 2010;25(Suppl 1):S144–S148.CrossRefPubMedGoogle Scholar
  41. 41.
    Camarero N, Mascaro C, Mayordomo C, Vilardell F, Haro D, Marrero PF. Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer. Mol Cancer Res. 2006;4:645–653.CrossRefPubMedGoogle Scholar
  42. 42.
    Benarafa C, Priebe GP, Remold-O’Donnell E. The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infection. J Exp Med. 2007;204:1901–1909.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Liu BG, Cao YB, Cao YY, et al. Altered protein profile of lymphocytes in an antigen-specific model of colitis: a comparative proteomic study. Inflamm Res. 2007;56:377–384.CrossRefPubMedGoogle Scholar
  44. 44.
    Choi DS, Kim DK, Kim YK, Gho YS. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics. 2013;13:1554–1571.CrossRefPubMedGoogle Scholar
  45. 45.
    Singh PP, Smith VL, Karakousis PC, Schorey JS. Exosomes isolated from mycobacteria-infected mice or cultured macrophages can recruit and activate immune cells in vitro and in vivo. J Immunol. 2012;189:777–785.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Leoni G, Neumann PA, Kamaly N, et al. Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest. 2015;125:1215–1227.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Wong WY, Lee MM, Chan BD, et al. Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages. Proteomics. 2016;16:1131–1145.CrossRefPubMedGoogle Scholar
  48. 48.
    Zheng X, Chen F, Zhang Q, et al. Salivary exosomal PSMA7: a promising biomarker of inflammatory bowel disease. Protein Cell. 2017. doi:10.1007/s13238-017-0413-7.PubMedCentralGoogle Scholar
  49. 49.
    Zhang XJ, Leung FP, Hsiao WW, et al. Proteome profiling of spinal cord and dorsal root ganglia in rats with trinitrobenzene sulfonic acid-induced colitis. World J Gastroenterol. 2012;18:2914–2928.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Barnett MP, Cooney JM, Dommels YE, et al. Modulation of colonic inflammation in Mdr1a(−/−) mice by green tea polyphenols and their effects on the colon transcriptome and proteome. J Nutr Biochem. 2013;24:1678–1690.CrossRefPubMedGoogle Scholar
  51. 51.
    Bertrand J, Marion-Letellier R, Azhar S, et al. Glutamine enema regulates colonic ubiquitinated proteins but not proteasome activities during TNBS-induced colitis leading to increased mitochondrial activity. Proteomics. 2015;15:2198–2210.CrossRefPubMedGoogle Scholar
  52. 52.
    Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das PK. Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. Br J Pharmacol. 2003;139:209–218.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Wenner BR, Lynn BC. Factors that affect ion trap data-dependent MS/MS in proteomics. J Am Soc Mass Spectrom. 2004;15:150–157.CrossRefPubMedGoogle Scholar
  54. 54.
    Law KP, Lim YP. Recent advances in mass spectrometry: data independent analysis and hyper reaction monitoring. Expert Rev Proteom. 2013;10:551–566.CrossRefGoogle Scholar
  55. 55.
    Doerr A. DIA mass spectrometry. Nat Meth. 2015;12:35.CrossRefGoogle Scholar
  56. 56.
    Plumb RS, Johnson KA, Rainville P, et al. UPLC/MS(E); a new approach for generating molecular fragment information for biomarker structure elucidation. Rapid Commun Mass Spectrom. 2006;20:1989–1994.CrossRefPubMedGoogle Scholar
  57. 57.
    Gillet LC, Navarro P, Tate S, et al. Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteom. 2012;11(O111):016717.Google Scholar
  58. 58.
    Angel PM, Baldwin HS, Gottlieb Sen D, et al. Advances in MALDI imaging mass spectrometry of proteins in cardiac tissue, including the heart valve. Biochim Biophys Acta. 2017. doi:10.1016/j.bbapap.2017.03.009.PubMedGoogle Scholar
  59. 59.
    Dreisewerd K. Recent methodological advances in MALDI mass spectrometry. Anal Bioanal Chem. 2014;406:2261–2278.CrossRefPubMedGoogle Scholar
  60. 60.
    Spengler B, Hubert M. Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass spectrometry: instrumentation for sub-micrometer resolved LDI and MALDI surface analysis. J Am Soc Mass Spectrom. 2002;13:735–748.CrossRefPubMedGoogle Scholar
  61. 61.
    Wasinger VC, Zeng M, Yau Y. Current status and advances in quantitative proteomic mass spectrometry. Int J Proteom. 2013;2013:180605.CrossRefGoogle Scholar
  62. 62.
    Hettich RL, Pan C, Chourey K, Giannone RJ. Metaproteomics: harnessing the power of high performance mass spectrometry to identify the suite of proteins that control metabolic activities in microbial communities. Anal Chem. 2013;85:4203–4214.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Wilk JN, Bilsborough J, Viney JL. The mdr1a−/− mouse model of spontaneous colitis: a relevant and appropriate animal model to study inflammatory bowel disease. Immunol Res. 2005;31:151–159.CrossRefPubMedGoogle Scholar
  64. 64.
    Fiebiger U, Bereswill S, Heimesaat MM. Dissecting the interplay between intestinal microbiota and host immunity in health and disease: lessons learned from germfree and gnotobiotic animal models. Eur J Microbiol Immunol (Bp). 2016;6:253–271.CrossRefGoogle Scholar
  65. 65.
    Ladiges WC. Mouse models of XRCC1 DNA repair polymorphisms and cancer. Oncogene. 2006;25:1612–1619.CrossRefPubMedGoogle Scholar
  66. 66.
    Oostenbrug LE, Dijkstra G, Nolte IM, et al. Absence of association between the multidrug resistance (MDR1) gene and inflammatory bowel disease. Scand J Gastroenterol. 2006;41:1174–1182.CrossRefPubMedGoogle Scholar
  67. 67.
    Ardizzone S, Maconi G, Bianchi V, et al. Multidrug resistance 1 gene polymorphism and susceptibility to inflammatory bowel disease. Inflamm Bowel Dis. 2007;13:516–523.CrossRefPubMedGoogle Scholar
  68. 68.
    Krupoves A, Seidman EG, Mack D, et al. Associations between ABCB1/MDR1 gene polymorphisms and Crohn’s disease: a gene-wide study in a pediatric population. Inflamm Bowel Dis. 2009;15:900–908.CrossRefPubMedGoogle Scholar
  69. 69.
    Zintzaras E. Is there evidence to claim or deny association between variants of the multidrug resistance gene (MDR1 or ABCB1) and inflammatory bowel disease? Inflamm Bowel Dis. 2012;18:562–572.CrossRefPubMedGoogle Scholar
  70. 70.
    Whiteaker JR, Lin C, Kennedy J, et al. A targeted proteomics-based pipeline for verification of biomarkers in plasma. Nat Biotechnol. 2011;29:625–634.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Fadi H. Mourad
    • 1
    • 2
  • Yunki Yau
    • 2
  • Valerie C. Wasinger
    • 3
  • Rupert W. Leong
    • 2
  1. 1.Department of Internal Medicine, Faculty of MedicineAmerican University of BeirutBeirutLebanon
  2. 2.Gastroenterology and Liver ServicesConcord Repatriation General HospitalConcordAustralia
  3. 3.Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical CentreThe University of NSW AustraliaKensingtonAustralia

Personalised recommendations