Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574, Japan.
Hepatol Res. 2006 Feb;34(2):99-103. doi: 10.1016/j.hepres.2005.11.006. Epub 2006 Jan 6.
Aquaporins (AQPs) are the channel forming membranous proteins involved in the biliary physiological homeostasis. Recently, we have reported the heterogeneous expression of AQPs in intrahepatic biliary epithelial cells or cholangiocytes in mice. However, the involvements of AQPs in hepatobiliary disorder are still unclear. Thus, we hypothesized that the AQP protein expressions are altered in human cholestatic disorders.
The AQP expressions of the immortalized human cholangiocytes cell line (H69) were assessed by immunoblotting. The expression of AQPs in liver biopsy specimens from various human cholestatic diseases as well as viral hepatitis were evaluated immunohistochemically. The degrees of staining were classified into four grades by comparison with staining intensity from controls.
AQP1 expression, predominantly membranous, was confirmed by immunoblotting analysis. However, the other subtypes of AQP expression were not detected. In human pathological tissues, AQP1 expression by interlobular bile ducts was similar to normal and viral hepatitis, although this expression was attenuated according to bile duct injuries in PBC. On the contrary, the AQP1 expression by proliferating bile ductile (equivalent for small cholangiocytes) was enhanced. In intrahepatic cholestasis, AQP1 expressions were diminished, which was further associated with the aberrant expressions by periportal hepatocytes.
AQP1 was expressed intensely in smaller proliferating bile ducts in human cholestatic liver disease. Also, the AQP1 expression was decreased in injured duct cells undergoing degeneration in PBC. The AQP1 expression was decreased in intrahepatic cholestasis probably due to negative feed back of the decreased bile flow. The role of AQP expression profiles may help the understanding of the pathogenesis of human cholestatic liver diseases.
水通道蛋白（AQP）是参与胆汁生理稳态的形成通道的膜蛋白。最近，我们报道了 AQP 在小鼠肝内胆管上皮细胞或胆管细胞中的异质性表达。然而，AQP 在肝胆疾病中的作用仍不清楚。因此，我们假设 AQP 蛋白表达在人类胆汁淤积性疾病中发生改变。
通过免疫印迹评估永生人胆管细胞系（H69）的 AQP 表达。通过免疫组织化学评估各种人类胆汁淤积性疾病和病毒性肝炎肝活检标本中 AQP 的表达。通过与对照的染色强度比较，将染色程度分为四级。
通过免疫印迹分析证实了 AQP1 的表达，主要为膜性。然而，其他 AQP 亚型的表达未被检测到。在人类病理组织中，小叶间胆管的 AQP1 表达与正常和病毒性肝炎相似，尽管在 PBC 中根据胆管损伤其表达减弱。相反，增殖胆管的 AQP1 表达增强（相当于小胆管细胞）。在肝内胆汁淤积中，AQP1 的表达减少，这与门脉周围肝细胞的异常表达进一步相关。
在人类胆汁淤积性肝病中，较小的增殖胆管中强烈表达 AQP1。此外，在 PBC 中发生退化的损伤胆管细胞中 AQP1 的表达减少。肝内胆汁淤积中 AQP1 的表达减少可能是由于胆汁流量减少的负反馈。AQP 表达谱的作用可能有助于理解人类胆汁淤积性肝病的发病机制。
