BACKGROUND AND AIMS

Defects in mucus and intestinal epithelia can lead to intestinal inflammation in colitis. Reduced peroxisome proliferator-activated receptor gamma (PPAR) in the mucosa may contribute to inflammation. However, the roles of PPAR in the intestinal barrier remain poorly understood.

METHODS

Chronic colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium (DSS) for 27 days. Three days before DSS treatment, mice were treated with the PPAR agonist rosiglitazone (Ro) orally at 20 mg kg day.

RESULTS

The colitis based on disease activity index and colonic histopathology was significantly ameliorated in the DSS + Ro group. Additionally, mice in the DSS + Ro group had a thicker mucous layer than those in DSS + NS group, and muc2 mRNA expression was elevated significantly along with the mouse atonal homolog, SAM-pointed domain-containing Ets-like factor, and anterior gradient 2 genes. Moreover, tight junctions were up-regulated, whereas long myosin light chain kinase and phosphorylation of the myosin II light chain were lower in DSS + Ro mice. Similarly, after HT-29 and Caco-2 cells were treated by LPS or LPS + Ro, PPAR activation by Ro could effectively improve the intestinal barrier, including intestinal mucus and tight junctions.

CONCLUSIONS

Our results demonstrate that activated PPAR could effectively promote intestinal mucus integrity by increasing the number of goblet cells, the glycosylation of mucins, and tight junctions via an MLCK-dependent mechanism.