Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis

J Surg Res. 2007 Jun 1;140(1):12-9. doi: 10.1016/j.jss.2006.07.050. Epub 2007 Apr 6.


Background: Inflammatory bowel disease (IBD) is associated with increased intestinal permeability and decreased expression of tight junction (TJ) proteins in the inflamed mucosa. Whether this alteration in TJ expression is a prerequisite for the development of intestinal inflammation or a secondary result of that inflammation is unknown. This study looked at the expression of the TJ protein ZO-1 and the corresponding permeability changes in dextran sulfate sodium (DSS) induced colitis in a mouse model.

Materials and methods: BALB/c mice were fed 3% DSS or water for 1, 3, 5, or 7 days. The animals were weighed, stool was checked for blood, and the colon length measured. Segments of the colon were used for histology, immunohistochemistry for ZO-1, or Western blot for TJ proteins. Colonic permeability was measured using Evan's Blue dye.

Results: DSS treated animals had heme positive stools, colitis by histology, significant weight loss, and colon shortening. There was an absence of ZO-1 by Western blot in the 7-day DSS treated animals, double the amount of claudin-1 and normal cytokeratin. The loss of ZO-1 started after 1 d of DSS treatment and was followed by a significant increase in permeability to Evan's blue by day 3.

Conclusions: The loss of ZO-1 and increased permeability preceded the development of significant intestinal inflammation suggesting that in DSS colitis alterations in the TJ complex occur before the intestinal inflammation and not as a consequence of it. These changes in the TJ complex may facilitate the development of the inflammatory infiltrate seen in colitis.

MeSH terms

  • Animals
  • Anticoagulants
  • Blotting, Western
  • Colitis / chemically induced
  • Colitis / metabolism*
  • Colitis / pathology*
  • Colon / metabolism
  • Colon / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Feces
  • Female
  • Fluorescent Antibody Technique
  • Gastrointestinal Hemorrhage / metabolism
  • Gastrointestinal Hemorrhage / pathology
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Phosphoproteins / metabolism*
  • Tight Junctions / metabolism*
  • Tight Junctions / pathology*
  • Weight Loss
  • Zonula Occludens-1 Protein


  • Anticoagulants
  • Membrane Proteins
  • Phosphoproteins
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein
  • Dextran Sulfate