Aquaporin-1 is associated with arterial capillary proliferation and hepatic sinusoidal transformation contributing to portal hypertension in primary biliary cirrhosis

Abstract

Although aquaporins (AQPs) in normal hepatobiliary system have been studied, little is known about AQP localization and changes in the hepatic microvascular system including sinusoids in cholestatic liver. The present study aimed to clarify the localization of AQP-1 in the microvessels in normal human liver and in primary biliary cirrhosis (PBC). Human normal liver (control) and PBC liver specimens were obtained. Immunohistochemistry, Western blotting, in situ hybridization (ISH) and electron microscopic examination for AQP-1 were conducted. In control liver and stages I-II PBC liver, AQP-1 immunoreactivity was mainly localized in portal venules, hepatic arterioles and bile ducts in the portal tract, but was hardly detected in the sinusoids. However, AQP-1 expression was enhanced in the proliferated bile ductules in PBC. In stages III-IV PBC liver tissues, AQP-1 was aberrantly expressed in proliferated arterial capillaries opening into the sinusoids at the peripheral edge of regenerating hepatic nodules and in the fibrotic septa. Overexpression of AQP-1 at protein and mRNA levels was demonstrated by Western blot and ISH, respectively. Angiogenetic and fibrotic responses are probably induced by AQP-1, leading to enhanced pouring of arterial blood into the sinusoids; thus, contributing to progression of portal hypertension in PBC.