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

PLoS One. 2013 Jul 23;8(7):e68876. doi: 10.1371/journal.pone.0068876. Print 2013.


Introduction: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis*
  • Chronic Disease
  • Colitis / chemically induced
  • Colitis / complications
  • Colitis / diagnosis*
  • Connective Tissue
  • Crohn Disease / diagnosis*
  • Crohn Disease / etiology
  • Dextran Sulfate / toxicity*
  • Female
  • Fibrosis / diagnosis*
  • Fibrosis / etiology
  • Gene Expression Profiling
  • Humans
  • Immunoenzyme Techniques
  • Inflammation / diagnosis*
  • Inflammation / etiology
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Recurrence
  • Wound Healing


  • Biomarkers
  • Dextran Sulfate

Grants and funding

This work was supported by a grant from the Broad Medical Research Program of the Broad Foundation (IBD-0319R). Christine Breynaert is supported by a grant of the Agency for Innovation by Science and Technology in Flanders (IWT). Ingrid Arijs is supported by a postdoctoral grant of the Foundation for Scientific Research Flanders, FWO Vlaanderen. Gert Van Assche and Séverine Vermeire are supported by the Foundation for Scientific Research Flanders, FWO Vlaanderen. Tom Dresselaers and Uwe Himmelreich are supported by the KU Leuven CoE ‘MoSAIC’ and the program financing ‘IMIR’. The authors state that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.