Molecular advances in autosomal dominant polycystic kidney disease.
Molecular advances in autosomal dominant polycystic kidney disease.
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DOI：
10.1053/j.ackd.2010.01.002
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发表时间：
2010-03
影响因子：
2.9
通讯作者：
Somlo S
中科院分区：
文献类型：
--
作者：
Gallagher AR;Germino GG;Somlo S
常染色体显性遗传性多囊性疾病（ADPKD）是导致肾衰竭的遗传性肾病的最常见形式。自从发现了两个致病基因PKD 1或PKD 2以来，对ADPKD发病机制的理解已经取得了显著进展。显性遗传基因突变，随后是体细胞二次突变，使相应基因的正常拷贝失活，导致肾小管囊肿形成，使肾脏变形并最终损害其功能。各自的基因产物多囊蛋白-1和多囊蛋白-2在共同的细胞途径中一起起作用。多囊蛋白-1是一种大的受体分子，与多囊蛋白-2形成受体通道复合物，多囊蛋白-2是属于TRP家族的阳离子通道。两种多囊蛋白都定位于初级纤毛，一种基于非运动微管的结构，其从管状细胞的顶膜延伸到管腔中。在这里，我们讨论了最近的见解ADPKD的发病机制，包括ADPKD的遗传学，各自的多囊蛋白的性质，纤毛的作用，和一些细胞信号通路，已牵连到PKD 1和PKD 2相关的途径。
Autosomal dominant polycystic disease (ADPKD) is the most common form of inherited kidney disease that results renal failure. The understanding the pathogenesis of ADPKD has advanced significantly since the discovery of the two causative genes, PKD1 or PKD2. Dominantly inherited gene mutations followed by somatic second hit mutations inactivating the normal copy of the respective gene result in renal tubular cyst formation that deforms the kidney and eventually impairs its function. The respective gene products, polycystin-1 and polycystin-2, work together in a common cellular pathway. Polycystin-1, a large receptor molecule, forms a receptor-channel complex with polycystin-2, which is a cation channel belonging to the TRP family. Both polycystin proteins have been localized to the primary cilium, a non-motile microtubule based structure that extends from the apical membrane of tubular cells into the lumen. Here we discuss recent insights in the pathogenesis of ADPKD including the genetics of ADPKD, the properties of the respective polycystin proteins, the role of cilia, and some cell signaling pathways that have been implicated in the pathways related to PKD1 and PKD2.
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