Requirement of cellular prion protein for intestinal barrier function and mislocalization in patients with inflammatory bowel disease

Abstract

Background & Aims: Cell adhesion is one function regulated by cellular prion protein (PrPc), a ubiquitous, glycosylphosphatidylinositol- anchored glycoprotein. PrPc is located in cell-cell junctions and interacts with desmosome proteins in the intestinal epithelium. We investigated its role in intestinal barrier function. Methods: We analyzed permeability and structure of cell-cell junctions in intestine tissues from PrPc knockout (PrPc-/-) and wild-type mice. PrPc expression was knocked down in cultured human Caco-2/TC7 enterocytes using small hairpin RNAs. We analyzed colon samples from 24 patients with inflammatory bowel disease (IBD). Results: Intestine tissues from PrPc-/- mice had greater paracellular permeability than from wild-type mice (105.9 ± 13.4 vs 59.6 ± 10.1 mg/mL fluorescein isothiocyanate-dextran flux; P