Open AccessProtein kinase C iota in the intestinal epithelium protects against dextran sodium sulfate‐induced colitis
Author(s) -
Calcagno Shelly R.,
Li Shuhua,
Shahid Muhammad W.,
Wallace Michael B.,
Leitges Michael,
Fields Alan P.,
Murray Nicole R.
Publication year - 2011
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.21547
Subject(s) - intestinal epithelium , colitis , protein kinase c , intestinal mucosa , barrier function , epithelium , inflammation , wound healing , inflammatory bowel disease , immunology , cancer research , kinase , medicine , chemistry , biology , microbiology and biotechnology , pathology , disease
Background: The integrity of the intestinal epithelium is critical for the absorption and retention of fluid and nutrients. The intestinal epithelium also provides a barrier between the intestinal bacteria and the body's immune surveillance. Therefore, intestinal epithelial barrier function is critically important, and disruption of the intestinal epithelium results in rapid repair of the damaged area. Methods: We evaluated the requirement for protein kinase C iota (PKCι) in intestinal epithelial homeostasis and response to epithelial damage using a well‐characterized mouse model of colitis. Mice were analyzed for the clinical, histological, and cellular effects of dextran sodium sulfate (DSS) treatment. Results: Knockout of the mouse PKCι gene ( Prkci ) in the intestinal epithelium ( Prkci KO mice) had no effect on normal colonic homeostasis; however, Prkci KO mice were significantly more sensitive to DSS‐induced colitis and death. After withdrawal of DSS, Prkci KO mice exhibited a continued increase in apoptosis, inflammation, and damage to the intestinal microvasculature and a progressive loss of trefoil factor 3 (TFF3) expression, a regulatory peptide important for intestinal wound healing. Knockdown of PKCι expression in HT‐29 cells reduced wound healing and TFF3 expression, while addition of exogenous TFF3 restored wound healing in PKCι‐depleted cells. Conclusions: Expression of PKCι in the intestinal epithelium protects against DSS‐induced colitis. Our data suggest that PKCι reduces DSS‐induced damage by promoting intestinal epithelial wound healing through the control of TFF3 expression. (Inflamm Bowel Dis 2010;)