EXPRESSION OF TIGHT JUNCTION PROTEINS IN DISEASES WITH COMPROMISED INTESTINAL BARRIER FUNCTION

Abstract

Background: The relationship between the increased intestinal permeability observed in several acute and chronic diseases and the expression of tight junctions (TJ) proteins is not well established. Our aim was to investigate the expression at transcriptional level of 3 transmembrane TJ proteins, Occludin, Claudin-1, Claudin-2 and of 2 scaffold TJ proteins, zonula occludens-1 (ZO-1) and Myosin 9B in intestinal biopsies from patients affected by celiac disease (CD), Crohn's disease (CrD), peptic ulcer disease (PUD) and type 1 diabetes (IDDM). Methods: Samples of small intestinal mucosa were taken from the second/third portion of the duodenum from all the subjects studied. After total RNA extraction and cDNA synthesis, quantitative real time polymerase chain reaction assays with SYBR Green was performed. Data were normalized by using18S rRNA as standard. Results: Shown in the Table. A significant down-regulation of all 5 genes studied was observed in patients affected by celiac disease before gluten-free diet, while no significant change was observed in IDDM patients.TableConclusions: The down-regulation of TJ transmembrane or/and intracellular components observed in all but IDDM might explain the increased intestinal permeability reported in these pathological conditions. The meaning of TJs disruption in the pathogenesis of each of this pathological condition warrants further investigation. The normal transcriptional level observed in celiacs on GFD suggests that the down-regulation of TJs in CD is reversible and secondary to gliadin exposure rather than to a genetic predisposition.