Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension

Urotensin II (UII) and its receptor (UT or GPR14) are involved in liver fibrosis and portal hypertension. Nevertheless, expression of the UII/UT system in the liver of patients with portal hypertension has not been elucidated. UII and UT gene expression were quantified in liver biopsy samples from patients with hepatitis-B-virus-associated cirrhosis and portal hypertension, and from normal controls by using quantitative real-time PCR. The liver distribution of UT was determined by means of immunohistochemistry and immunofluorescence. Western blot analysis was used to assess liver levels of UT. Simultaneously, we measured intra-operative free portal venous pressure (FPVP) and collected plasma for UII measurement by ELISA. UT expression at the mRNA and protein level was enhanced significantly in the liver of patients with cirrhosis and portal hypertension, compared with that in healthy controls. UT protein expression was concentrated mainly in the Kupffer cells and sinusoidal endothelial cells. In cirrhotic tissue, UII gene expression was increased 5-fold in comparison to that in normal liver tissue. Plasma UII level was higher in cirrhotic patients compared with controls and was correlated with FPVP (r=0.807; P<0.001) and UII mRNA in the liver (r=0.802; P<0.001). These findings suggest that the intrahepatic UII/UT system has an important pathophysiological role in cirrhosis and portal hypertension.