Protein kinase C iota in the intestinal epithelium protects against dextran sodium sulfate-induced colitis

Shelly R. Calcagno, Shuhua Li, Muhammad W. Shahid, Michael B. Wallace, Michael Leitges, Alan P. Fields, Nicole R. Murray

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 (PKCl) 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 PKCl 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 PKCl expression in HT-29 cells reduced wound healing and TFF3 expression, while addition of exogenous TFF3 restored wound healing in PKCl-depleted cells. Conclusions: Expression of PKCl in the intestinal epithelium protects against DSS-induced colitis. Our data suggest that PKCl reduces DSS-induced damage by promoting intestinal epithelial wound healing through the control of TFF3 expression.

Original languageEnglish (US)
Pages (from-to)1685-1697
Number of pages13
JournalInflammatory bowel diseases
Volume17
Issue number8
DOIs
StatePublished - Aug 1 2011

Keywords

  • apoptosis
  • colitis
  • dextran sodium sulfate
  • permeability
  • protein kinase C iota
  • trefoil factor 3
  • wound healing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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