title: Protein kinase C iota in the intestinal epithelium protects against dextran sodium sulfate-induced colitis.
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 (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.
authors: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, USA.
authors: Shelly R
authors: SR
authors: Calcagno
authors: Shuhua
authors: S
authors: Li
authors: Muhammad W
authors: MW
authors: Shahid
authors: Michael B
authors: MB
authors: Wallace
authors: Michael
authors: M
authors: Leitges
authors: Alan P
authors: AP
authors: Fields
authors: Nicole R
authors: NR
authors: Murray
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D003106:Colon / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D016264:Dextran Sulfate; D005260:Female; D019073:HT29 Cells; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology* / Q000503:physiopathology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055806:Microvessels / Q000473:pathology; D009077:Mucins / Q000378:metabolism* / Q000502:physiology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071165:Trefoil Factor-3; D014945:Wound Healing; D000099293:Protein Kinase C-lambda
chemical_list: D016264:Dextran Sulfate; D007527:Isoenzymes; D009077:Mucins; D011493:Protein Kinase C; D000071165:Trefoil Factor-3; D000099293:Protein Kinase C-lambda; C493263:Tff3 protein, mouse