Study on Role and Mechanism of Claudin-2 in Formation of Cholesterol Gallstone / 胃肠病学

ABSTRACT

Background: Claudin protein family is an important component for construction of tight cell junction. Claudin-2 is a forming protein of paracellular channel and is highly expressed in hepatocytes and bile duct cells, which has selective permeability of water molecules and cations. Claudin-2 plays a vital role in the physiological regulation of digestive and urinary systems. Aims: To investigate the role and mechanism of claudin-2 in formation of cholesterol gallstone and bile secretion. Methods: Liver and gallbladder tissues from claudin-2 knockout (Cldn-2-/-) and wild type (Cldn-2+/+) mice were collected. Expressions of claudin family protein were determined by Western blotting. HE staining, immunofluorescence staining, electron microscope were used to analyze the effect of claudin-2 gene knockout on liver and gallbladder tissue structure. Regulatory roles of claudin-2 in bile component and flow were analyzed. Results: Claudin family proteins were highly expressed in liver and gallbladder tissue in Cldn-2+/+ mice. No significant difference in structure of liver and gallbladder tissue was found between Cldn-2-/- mice and Cldn-2+/+ mice. Compared with Cldn-2+/+ mice, bile flow rate was significantly decreased (P<0.05), concentration of bile was significantly increased (P<0.05), and contents of bile acid, cholesterol, bilirubin, phospholipid in liver and gallbladder bile were significantly increased in Cldn-2-/- mice (P<0.05). Conclusions: Claudin-2 regulates paracellular water flow which is required for proper regulation of bile composition and flow. Dysregulation of this process increases the susceptibility to cholesterol gallstone related diseases in mice.