Aquaporin-1 associated with hepatic arterial capillary proliferation on hepatic sinusoid in human cirrhotic liver

• Published in: Liver international Vol. 31; no. 10; pp. 1554 - 1564
• Main Authors: Yokomori, Hiroaki, Oda, Masaya, Yoshimura, Kazunori, Kaneko, Fumihiko, Hibi, Toshifumi
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-11-2011
• Subjects: Aged; Analysis of Variance; Aquaporin 1 - metabolism; Aquaporin-1; Biopsy; Blotting, Western; Capillaries - growth & development; Capillaries - ultrastructure; DNA Primers - genetics; Endothelial Cells - metabolism; hepatic arterial capillary; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; In Situ Hybridization; Laser Capture Microdissection; Liver - blood supply; liver cirrhosis; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Microscopy, Electron, Transmission; Middle Aged; Neovascularization, Pathologic - metabolism; portal hypertension; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2011.02610.x

Background
Aquaporins (AQPs) are key regulators not only of water transport in the cytoplasm but also of angiogenesis. Although AQPs in the normal hepatobiliary system have been studied in mammals, little is known about the localization and changes of AQPs in the hepatic microvascular system including sinusoids in cirrhotic liver, which might contribute to portal hypertension.
Aims
We designed this study to examine the localization of AQP1 in human cirrhotic liver.
Methods
Surgical wedge biopsy specimens were obtained from non‐cirrhotic portions of human livers (normal control) and from cirrhotic livers (LC) (Child A‐LC and Child C‐LC). Immunostaining, Western blotting, in situ hybridization (ISH) and laser‐captured microdissection (LCM) were conducted.
Results
In control liver tissue, AQP1 was localized mainly in the portal venules, hepatic arterioles and bile ducts in the portal tract, although AQP1 was detected only slightly in the sinusoids. In cirrhotic liver tissue, AQP1 expression was evident, aberrantly observed on periportal sinusoidal endothelial cells corresponding to the capillarized sinusoids, on the proliferated arterial capillaries opening into the sinusoid in the generating hepatic nodule and on proliferated bile ductules at the peripheral edge of nodules and fibrotic septa. In cirrhotic liver, overexpression of AQP1 at protein and mRNA levels was demonstrated, respectively, using Western blot and ISH. AQP‐1 of mRNA level in sinusoid was confirmed using LCM.
Conclusions
Aberrant expressions of AQP1 in periportal sinusoidal regions in human cirrhotic liver indicate the proliferation of arterial capillaries directly connected to the sinusoids, contributing to microvascular resistance in cirrhosis.