Altered intestinal tight junctions’ expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability

作者：Stelios F. Assimakopoulos, Athanassios C. Tsamandas, Georgios I. Tsiaoussis, Elli Karatza, Christos K Triantos, Constantine Vagianos, Iris Spiliopoulou, Valeria Kaltezioti, ARISTIDIS S. CHARONIS, Vassiliki N. Nikolopoulou, Chrisoula D. Scopa, Konstantinos C. Thomopoulos · 发表于：European Journal of Clinical Investigation · 年份：2011 · DOI：10.1111/j.1365-2362.2011.02609.x · 被引用次数：165 · 研究领域：Barrier Structure and Function Studies、Liver Disease and Transplantation、Gut microbiota and health

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. This study was designed to investigate whether the expression of tight junction (TJ) proteins, which regulate gut paracellular permeability, is altered in the intestinal mucosa of patients with liver cirrhosis and study its potential association with the stage of liver disease and the development of systemic endotoxemia. DESIGN: Twenty-four patients with cirrhosis 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 TJ proteins occludin and claudin-1 in the intestinal epithelium was evaluated by immunohistochemistry. Plasma endotoxin concentrations were also determined. RESULTS: Patients with cirrhosis 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 patients with cirrhosis, a specific patt...