Altered Intestinal Tight Junctions' Expression in Patients with Liver Cirrhosis: A Pathogenetic Mechanism of Intestinal Hyperpermeability
Stelios Asimakopoulos, Athanassios Tsamandas, George Tsiaoussis, Eli Karatza, Constantine Vagianos, Iris Spiliopoulou, Valeria Kaltezioti, Aristides Charonis, Vassiliki Nikolopoulou, Konstantinos Thomopoulos, Chrisoula Scopa. University of Patras Medical School, Patras, Greece; Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Background: Increased intestinal permeability in cirrhosis exerts a pivotal role in the pathogenesis of spontaneous bacterial peritonitis and other complications of cirrhosis through promotion of systemic endotoxemia. The present study was designed to investigate whether alterations of tight junction associated proteins in the intestinal epithelium are involved, at the molecular lever, in intestinal hyperpermeabilty observed in cirrhotic patients.
Design: Twenty four cirrhotic patients at a decompensated (n=12, group A) or compensated condition (n=12, group B) and 12 healthy controls (group C) were subjected to duodenal biopsy. The expression of the tight junction (TJ) proteins occludin and claudin-1 in the intestinal epithelium was evaluated by immunohistochemistry. Plasma endotoxin concentrations were also determined.
Results: Cirrhotic patients presented significantly higher serum endotoxin concentrations as compared to healthy controls (P<0.001), whilst endotoxemia was higher in decompensated disease (P<0.05 vs. compensated cirrhosis). Patients with decompensated and compensated cirrhosis presented significantly reduced expression of occludin and claudin-1 as compared to controls (P<0.01, respectively). These alterations were significantly more pronounced in decompensated patients as compared to compensated (P<0.05). Regarding occludin, in cirrhotic patients a specific pattern of expression in the intestinal epithelium was observed, with a gradually increasing loss of expression from crypt to tip of the villi.
Conclusions: The present study demonstrates for the first time that human liver cirrhosis induces significant alterations of enterocytes' tight junctions. These changes might represent an important cellular mechanism for intestinal barrier dysfunction and hyperpermeability in patients with liver cirrhosis.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 78, Wednesday Morning