Autosomal-dominant polycystic kidney disease (ADPKD) is a disease of defective tissue homeostasis resulting in active remodeling of nephrons and bile ducts to form fluid-filled sacs called cysts. The causal genes PKD1 and PKD2 encode transmembrane proteins polycystin 1 (PC1) and polycystin 2 (PC2), respectively. Together, the polycystins localize to the solitary primary cilium that protrudes from the apical surface of most kidney tubule cells and is thought to function as a privileged compartment that the cell uses for signal integration of sensory inputs. It has been proposed that PC1 and PC2 form a receptor-channel complex that detects external stimuli and transmit a local calcium-mediated signal, which may control a multitude of cellular processes by an as-yet unknown mechanism. Genetic studies using mouse models of cilia and polycystin dysfunction have shown that polycystins regulate an unknown cilia-dependent signal that is normally part of the homeostatic maintenance of nephron structure. ADPKD ensues when this pathway is dysregulated by absence of polycystins from intact cilia, but disruption of cilia also disrupts this signaling mechanism and ameliorates ADPKD even in the absence of polycystins. Understanding the role of cilia and ciliary signaling in ADPKD is challenging, but success will provide saltatory advances in our understanding of how tubule structure is maintained in healthy kidneys and how disruption of polycystin or cilia function leads to the pathological tissue remodeling process underlying ADPKD.

中文翻译：

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多囊肾囊肿形成的纤毛机制。


常染色体显性多囊肾病 (ADPKD) 是一种组织稳态缺陷的疾病，导致肾单位和胆管主动重塑，形成充满液体的囊，称为囊肿。致病基因 PKD1 和 PKD2 分别编码跨膜蛋白多囊蛋白 1 (PC1) 和多囊蛋白 2 (PC2)。多囊蛋白一起定位于从大多数肾小管细胞的顶端表面突出的孤立的初级纤毛，并且被认为充当细胞用于感觉输入的信号整合的特权区室。有人提出，PC1 和 PC2 形成受体通道复合物，可检测外部刺激并传输局部钙介导的信号，该信号可能通过迄今未知的机制控制多种细胞过程。使用纤毛和多囊蛋白功能障碍的小鼠模型进行的遗传研究表明，多囊蛋白调节未知的纤毛依赖性信号，该信号通常是肾单位结构稳态维持的一部分。当该通路因完整纤毛中缺乏多囊蛋白而失调时，就会出现 ADPKD，但纤毛的破坏也会破坏这种信号机制，即使在缺乏多囊蛋白的情况下也会改善 ADPKD。了解纤毛和纤毛信号传导在 ADPKD 中的作用具有挑战性，但成功将为我们理解健康肾脏中如何维持肾小管结构以及多囊蛋白或纤毛功能的破坏如何导致 ADPKD 的病理组织重塑过程提供跳跃性进展。