title: Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn's disease.
abstract: BACKGROUND
  Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS) ingestion, to mimic the relapsing nature of the human disease.
  
  
  METHODS
  C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total). Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis.
  
  
  RESULTS
  Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn's colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS.
  
  
  CONCLUSIONS
  Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn's disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of inflammation and fibrosis.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Breynaert
authors.forename: Tom
authors.initials: T
authors.lastname: Dresselaers
authors.forename: Clémentine
authors.initials: C
authors.lastname: Perrier
authors.forename: Ingrid
authors.initials: I
authors.lastname: Arijs
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cremer
authors.forename: Leentje
authors.initials: L
authors.lastname: Van Lommel
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Steen
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.forename: Jan L
authors.initials: JL
authors.lastname: Ceuppens
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000175:diagnosis*; D003238:Connective Tissue; D003424:Crohn Disease / Q000175:diagnosis* / Q000209:etiology; D016264:Dextran Sulfate / Q000633:toxicity*; D005260:Female; D005355:Fibrosis / Q000175:diagnosis* / Q000209:etiology; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000175:diagnosis* / Q000209:etiology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012008:Recurrence; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D016264:Dextran Sulfate
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