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

Abstract

Abstract. 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 intraoperative 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.

Urotensin II in the development and progression of chronic kidney disease following ⅚ nephrectomy in the rat

“…Indeed, the kidney is a major source of UII in both humans (Shenouda, Douglas, Ohlstein, & Giaid, 2002) and rats (Song et al, 2006); in contrast, the primary source of URP is the brain (Sugo et al, myofibroblasts, leading to an accumulation of abnormal extracellular matrix components (Liu, 2006). Urotensin II has been shown to promote fibrosis in the heart (Bousette et al, 2006;Chen et al, 2008;Dai et al, 2007;Tran et al, 2010;Tzanidis et al, 2003), blood vessels (Zhao et al, 2013), lungs (Onat et al, 2012) and liver (Kemp et al, 2009;Liu et al, 2010). In streptozotocin-induced diabetic rats, UII and UT were upregulated in association with an increase in renal fibrosis and the accumulation of extracellular matrix components (Tian et al, 2008).…”