Qian Qi, Li Ming, Cai Yiqiang, Ward Christopher J, Somlo Stefan, Harris Peter C, Torres Vicente E
Division of Nephrology, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Am Soc Nephrol. 2003 Sep;14(9):2280-7. doi: 10.1097/01.asn.0000080185.38113.a3.
The leading cause of death in autosomal dominant polycystic kidney disease (ADPKD) is cardiovascular. However, little is known about the pathogenesis of these manifestations. The present study was undertaken to characterize the ADPKD proteins, the polycystins, in vascular smooth muscle cells. It was demonstrated that the expression of polycystin-1 is developmentally regulated, whereas polycystin-2 has a more constant level of expression. A polycystin-1 subpopulation was immunoprecipitated by polycystin-2, indicating an in vivo interaction of these two proteins. Analysis with glycosidase and cell surface biotinylation indicates that some polycystin-1 products, but not polycystin-2, are located on the plasma membrane. Immunofluorescence showed that most of the polycystin-1 and polycystin-2 was cytoplasmic but that persistent polycystin-1 staining was located in proximity to the cell surface after a Triton-X extraction, whereas no clear surface localization of polycystin-2 was detected. Immuno-gold electron microscopy revealed that polycystin-1 was localized at the plasma membrane and sarcoplasmic reticulum, whereas polycystin-2 was mainly located in the sarcoplasmic reticulum. Both polycystins were found to be associated with dense plaques. These observations are consistent with an important role of the polycystins in the development, maintenance, and function of the myoelastic arterial organization and with the vascular phenotype associated with ADPKD.
常染色体显性多囊肾病（ADPKD）的主要死因是心血管疾病。然而，对于这些表现的发病机制知之甚少。本研究旨在对血管平滑肌细胞中的ADPKD蛋白——多囊蛋白进行表征。结果表明，多囊蛋白-1的表达受发育调控，而多囊蛋白-2的表达水平较为恒定。多囊蛋白-2免疫沉淀了一部分多囊蛋白-1，表明这两种蛋白在体内存在相互作用。糖苷酶分析和细胞表面生物素化表明，一些多囊蛋白-1产物位于质膜上，而多囊蛋白-2则不然。免疫荧光显示，大多数多囊蛋白-1和多囊蛋白-2位于细胞质中，但在经Triton-X抽提后，多囊蛋白-1持续染色位于细胞表面附近，而未检测到多囊蛋白-2有明显的表面定位。免疫金电子显微镜显示，多囊蛋白-1定位于质膜和肌浆网，而多囊蛋白-2主要位于肌浆网。发现这两种多囊蛋白均与致密斑相关。这些观察结果与多囊蛋白在肌弹性动脉组织发育、维持和功能中的重要作用以及与ADPKD相关的血管表型一致。
