Intestinal epithelial cell proliferation, apoptosis and expression of tight junction proteins in patients with obstructive jaundice

Abstract

Intestinal hyperpermeability has been repeatedly confirmed in patients with obstructive jaundice and is considered a pivotal factor in the development of septic and renal complications in these patients. However, little is known on the mechanism(s) leading to this phenomenon. This study was undertaken to investigate the cellular and subcellular intestinal alterations in patients with obstructive jaundice. Sixteen patients with obstructive jaundice of malignant (n = 8, group A) or benign (n = 8, group B) aetiology, without concomitant cholangitis, and eight healthy controls (group C) were subjected to duodenal biopsy distal to the ampulla of Vater. Specimens were examined histologically and the apoptotic activity in the cryptal epithelium was recorded. Epithelial proliferation was evaluated by immunohistochemical expression of Ki67 antigen. The expression of the tight junction (TJ) proteins occludin, claudin-1, claudin-4 and claudin-7 in the intestinal epithelium was also evaluated by immunohistochemistry. Patients with malignant or benign obstructive jaundice presented significantly decreased intestinal epithelial cell proliferation rates compared with controls (P < 0·05), whereas no differences were detected in apoptotic activity. In a semiquantitative analysis of TJ protein expression, occludin, claudin-1 and -7 were significantly decreased (P < 0·001), whereas claudin-4 was significantly increased (P < 0·01) in jaundiced patients and their distribution was altered. No differences were detected between patients with malignant or benign obstructive jaundice for all intestinal barrier parameters studied. Decreased enterocyte proliferation and altered TJ protein expression might represent important mechanisms for intestinal barrier dysfunction and hyperpermeability in patients with extrahepatic cholestasis. The potential pharmacological modulation of these factors may lead to better control of intestinal permeability in the jaundiced patient with improved clinical outcome.