Burghardt B, Elkaer M-L, Kwon T-H, Rácz G Z, Varga G, Steward M C, Nielsen S
Molecular Oral Biology Research Group, Department of Oral Biology, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary.
Gut. 2003 Jul;52(7):1008-16. doi: 10.1136/gut.52.7.1008.
The exocrine pancreas secretes large volumes of isotonic fluid, most of which originates from the ductal system. The role of aquaporin (AQP) water channels in this process is unknown.
Expression and localisation of known AQP isoforms was examined in normal human pancreas, pancreatic adenocarcinoma, and pancreatic cell lines of ductal origin (Capan-1, Capan-2, and HPAF) using reverse transcriptase-polymerase chain reaction and immunohistochemistry.
Messenger RNAs for AQP1, -3, -4, -5, and -8 were detected in normal pancreas and in pancreatic adenocarcinoma. The cell lines expressed AQP3, -4, and -5 but lacked AQP1 and AQP8. Immunohistochemistry of normal pancreas revealed that AQP1 is strongly expressed in centroacinar cells and in both the apical and basolateral domains of intercalated and intralobular duct epithelia. AQP1 expression declined with distance along the small interlobular ducts and was not detectable in larger interlobular ducts. AQP3 and AQP4 were not detectable by immunohistochemistry. AQP5 was observed at the apical membrane of intercalated duct cells and also in duct associated mucoid glands. AQP8 was confined to the apical pole of acinar cells. Both AQP1 and AQP5 were colocalised with cystic fibrosis transmembrane conductance regulator (CFTR) at the apical membrane of intercalated duct cells.
AQP1 and AQP5 are strongly expressed in the intercalated ducts of the human pancreas. Their distribution correlates closely with that of CFTR, a marker of ductal electrolyte secretion. This suggests that fluid secretion is concentrated in the terminal branches of the ductal tree and that both AQP1 and AQP5 may play a significant role.
外分泌胰腺分泌大量等渗液,其中大部分源自导管系统。水通道蛋白(AQP)水通道在此过程中的作用尚不清楚。
使用逆转录聚合酶链反应和免疫组织化学法,检测已知AQP亚型在正常人类胰腺、胰腺腺癌以及导管起源的胰腺细胞系(Capan-1、Capan-2和HPAF)中的表达和定位。
在正常胰腺和胰腺腺癌中检测到AQP1、-3、-4、-5和-8的信使核糖核酸。这些细胞系表达AQP3、-4和-5,但缺乏AQP1和AQP8。正常胰腺的免疫组织化学显示,AQP1在中央腺泡细胞以及闰管和小叶内导管上皮的顶端和基底外侧区域强烈表达。AQP1的表达沿小叶间小导管距离下降,在较大的小叶间导管中无法检测到。免疫组织化学无法检测到AQP3和AQP4。在闰管细胞的顶端膜以及导管相关黏液腺中观察到AQP5。AQP8局限于腺泡细胞的顶端极。AQP1和AQP5在闰管细胞的顶端膜均与囊性纤维化跨膜传导调节因子(CFTR)共定位。
AQP1和AQP5在人类胰腺的闰管中强烈表达。它们的分布与导管电解质分泌标记物CFTR的分布密切相关。这表明液体分泌集中在导管树的终末分支,且AQP1和AQP5可能都发挥重要作用。