Devuyst O, Nielsen S, Cosyns J P, Smith B L, Agre P, Squifflet J P, Pouthier D, Goffin E
Department of Nephrology, University of Louvain Medical School, B-1200 Brussels, Belgium.
Am J Physiol. 1998 Jul;275(1):H234-42. doi: 10.1152/ajpheart.1998.275.1.H234.
Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endothelium of the peritoneum and is impaired in the case of peritoneal inflammation. The water channel aquaporin (AQP)-1 has been proposed to be the ultrasmall pore in animal models. To substantiate the role of AQP-1 in the human peritoneum, we investigated the expression of AQP-1, AQP-2, and endothelial nitric oxide synthase (eNOS) in 19 peritoneal samples from normal subjects (n = 5), uremic patients treated by hemodialysis (n = 7) or PD (n = 4), and nonuremic patients (n = 3), using Western blotting and immunostaining. AQP-1 is very specifically located in capillary and venule endothelium but not in small-size arteries. In contrast, eNOS is located in all types of endothelia. Immunoblot for AQP-1 in human peritoneum reveals a 28-kDa band (unglycosylated AQP-1) and diffuse bands of 35-50 kDa (glycosylated AQP-1). Although AQP-1 expression is remarkably stable in all samples whatever their origin, eNOS (135 kDa) is upregulated in the three patients with ascites and/or peritonitis (1 PD and 2 nonuremic patients). AQP-2, regulated by vasopressin, is not expressed at the protein level in human peritoneum. This study 1) supports AQP-1 as the molecular counterpart of the ultrasmall pore in the human peritoneum and 2) demonstrates that AQP-1 and eNOS are regulated independently of each other in clinical conditions characterized by peritoneal inflammation.
腹膜透析(PD)过程中的水转运需要腹膜毛细血管内皮上的超小孔道,而在腹膜炎症情况下这种转运功能会受损。在动物模型中,水通道水通道蛋白(AQP)-1被认为是这种超小孔道。为了证实AQP-1在人体腹膜中的作用,我们使用蛋白质印迹法和免疫染色法,研究了19份来自正常受试者(n = 5)、接受血液透析治疗的尿毒症患者(n = 7)或腹膜透析患者(n = 4)以及非尿毒症患者(n = 3)的腹膜样本中AQP-1、AQP-2和内皮型一氧化氮合酶(eNOS)的表达情况。AQP-1非常特异性地定位于毛细血管和小静脉内皮,而不在小动脉中。相比之下,eNOS存在于所有类型的内皮中。人体腹膜中AQP-1的免疫印迹显示出一条28 kDa的条带(未糖基化的AQP-1)和35 - 50 kDa的弥散条带(糖基化的AQP-1)。尽管无论样本来源如何,AQP-1的表达在所有样本中都非常稳定,但在3例有腹水和/或腹膜炎的患者(1例腹膜透析患者和2例非尿毒症患者)中,eNOS(135 kDa)表达上调。受血管加压素调节的AQP-2在人体腹膜中未检测到蛋白水平的表达。本研究1)支持AQP-1作为人体腹膜中超小孔道的分子对应物,2)表明在以腹膜炎症为特征的临床情况下,AQP-1和eNOS相互独立调节。