Genetics and pathogenesis of polycystic kidney disease
Genetics and pathogenesis of polycystic kidney disease
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DOI：
10.1097/01.asn.0000028643.17901.42
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发表时间：
2002-09-01
影响因子：
13.6
通讯作者：
Somlo, S
中科院分区：
文献类型：
--
作者：
Igarashi, P;Somlo, S
多囊肾病（PKD）是儿童和成人慢性肾衰竭的常见遗传原因，其特征是肾脏和其他器官中充满液体的囊肿积聚。肾囊肿起源于肾单位和肾收集系统的上皮，由单层细胞排列，细胞增殖率较高，比正常小管细胞分化程度低(1)。基因表达、细胞极性、液体分泌、细胞凋亡和细胞外基质的异常也被描述为PKD，但囊肿形成的机制仍不完全清楚（2-6）。最近几个月，我们对PKD的遗传学和发病机制的理解有了一些进展。人类和小鼠常染色体隐性PKD的基因已被克隆，PKD2基因产物已被确定为细胞内钙释放通道，PKD1基因产物已被发现调节细胞周期，而一个被忽视的细胞器，初级纤毛，已成为多囊病的潜在关键角色。在这篇综述中，我们将讨论人类PKD基因的克隆和动物模型的表征如何为PKD的发病机制提供新的见解。希望通过对PKD的遗传学和发病机制的深入了解，能够提高PKD的诊断和治疗水平。PKD可以遗传为常染色体显性性状（ADPKD）或常染色体隐性性状（ARPKD）（表1）。ADPKD是儿童和成人的常见病，而ARPKD不常见，主要发生在新生儿和儿童中。ADPKD是由16号染色体上的PKD1基因或4号染色体上的PKD2基因突变引起的。最近在6号染色体上发现了与ARPKD有关的基因PKHD1。肾囊肿也可与其他遗传性疾病（如结节性硬化症、希佩尔-林道病、齐ellweger综合征、幼年肾病）相关，但这里不作进一步讨论。
Polycystic kidney disease (PKD), a common genetic cause of chronic renal failure in children and adults, is characterized by the accumulation of fluid-filled cysts in the kidney and other organs. The renal cysts originate from the epithelia of the nephrons and renal collecting system and are lined by a single layer of cells that have higher rates of cellular proliferation and are less differentiated than normal tubular cells (1). Abnormalities in gene expression, cell polarity, fluid secretion, apoptosis, and extracellular matrix have also been described in PKD, but the mechanism of cyst formation remains incompletely understood (2–6). In recent months, there have been several advances in our understanding of the genetics and pathogenesis of PKD. Genes responsible for autosomal recessive PKD in humans and mice have been cloned, the PKD2 gene product has been identified as an intracellular calcium release channel, the PKD1 gene product has been found to regulate the cell cycle, and a neglected cellular organelle, the primary cilium, has emerged as a potential key player in polycystic disease. In this review, we will discuss how the cloning of the human PKD genes and the characterization of animal models have provided new insights into the pathogenesis of PKD. It is hoped that a more thorough understanding of the genetics and pathogenesis of PKD will lead to improvements in diagnosis and treatment. PKD can be inherited as an autosomal dominant trait (ADPKD) or an autosomal recessive trait (ARPKD)(Table 1). ADPKD is a common disease that occurs in both children and adults, whereas ARPKD is uncommon and occurs primarily in neonates and children. ADPKD is caused by mutations of either the PKD1 gene on chromosome 16 or the PKD2 gene on chromosome 4. The gene responsible for ARPKD (PKHD1) has recently been identified on chromosome 6. Renal cysts can also occur in association with other genetic diseases (eg, tuberous sclerosis, von Hippel-Lindau disease, Zellweger syndrome, juvenile nephronophthisis), but these entities will not be discussed further here.