Wang Shixuan, Luo Ying, Wilson Patricia D, Witman George B, Zhou Jing
Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Am Soc Nephrol. 2004 Mar;15(3):592-602. doi: 10.1097/01.asn.0000113793.12558.1d.
Recent evidence suggests that structural and functional abnormalities of primary cilia in kidney epithelia are associated with mouse and human autosomal dominant polycystic kidney disease. To determine whether fibrocystin/polyductin/tigmin (FPC), the protein product encoded by the PKHD1 gene that is responsible for autosomal recessive polycystic kidney disease among human subjects, is also a component of primary cilia in the kidney, antipeptide antibodies to the carboxyl-terminal intracellular domain and amino-terminal extracellular domain of FPC were generated and were characterized with immunoblotting and immuno-light and -electron microscopy. Immunolocalization in normal kidney tissue sections and cultured kidney cells demonstrated that FPC was localized to the primary cilia and concentrated on the basal bodies in both kidney tissue sections and cultured kidney cells. The FPC expression pattern was not altered in kidney cells with Pkd1 mutations. These findings suggest that FPC is a functional and/or structural component of primary cilia in kidney tubular cells. It is proposed that the pathogenesis of autosomal recessive polycystic kidney disease is linked to the dysfunction of primary cilia.
最近有证据表明，肾上皮细胞中初级纤毛的结构和功能异常与小鼠及人类常染色体显性多囊肾病有关。为了确定纤维囊素/多囊蛋白/条带蛋白（FPC）（一种由PKHD1基因编码的蛋白产物，在人类中导致常染色体隐性多囊肾病）是否也是肾初级纤毛的组成成分，研究人员制备了针对FPC羧基末端胞内结构域和氨基末端胞外结构域的抗肽抗体，并通过免疫印迹、免疫光学显微镜和免疫电子显微镜进行了表征。在正常肾组织切片和培养的肾细胞中的免疫定位显示，FPC定位于初级纤毛，并在肾组织切片和培养的肾细胞中均集中于基体。在具有Pkd1突变的肾细胞中，FPC的表达模式未发生改变。这些发现表明，FPC是肾小管细胞中初级纤毛的功能和/或结构成分。有人提出，常染色体隐性多囊肾病的发病机制与初级纤毛功能障碍有关。
