Department of Internal Medicine, Kitasato Medical Center Hospital, Kitasato University, Saitama, Japan.
Liver Int. 2011 Nov;31(10):1554-64. doi: 10.1111/j.1478-3231.2011.02610.x. Epub 2011 Jul 29.
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.
We designed this study to examine the localization of AQP1 in human cirrhotic liver.
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.
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.
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.
水通道蛋白（AQP）不仅是细胞质中水分运输的关键调节剂，也是血管生成的关键调节剂。虽然哺乳动物正常肝胆系统中的 AQP 已经得到研究，但对于包括肝硬化肝脏窦状隙在内的肝微血管系统中 AQP 的定位和变化知之甚少，这可能有助于门脉高压的形成。
本研究旨在检测 AQP1 在人肝硬化肝脏中的定位。
从非肝硬化部分的人肝脏（正常对照）和肝硬化肝脏（LC）（Child A-LC 和 Child C-LC）中获取手术楔形活检标本。进行免疫染色、Western blot、原位杂交（ISH）和激光捕获显微切割（LCM）。
在对照肝组织中，AQP1 主要定位于门脉小静脉、肝动脉和门脉小叶内胆管，但在窦状隙中仅检测到轻微的 AQP1。在肝硬化肝组织中，AQP1 的表达明显，在与毛细血管化窦状隙对应的门周窦状内皮细胞、在生成性肝结节中开口入窦状隙的增生性动脉毛细血管以及在结节和纤维性间隔的周边边缘处增生性胆管上观察到异常表达。通过 Western blot 和 ISH 分别显示了 AQP1 在蛋白和 mRNA 水平上的过表达。使用 LCM 证实了窦状隙中 AQP-1 的 mRNA 水平。
人肝硬化肝脏中门周窦状区 AQP1 的异常表达表明与窦状隙直接连接的动脉毛细血管的增殖，导致肝硬化时的微血管阻力增加。
