The pathogenesis of autosomal dominant polycystic kidney disease.
The pathogenesis of autosomal dominant polycystic kidney disease.
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常染色体显性多囊肾病的发病机制。
DOI：
10.1159/000093216
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Sutters,Michael
中科院分区：
文献类型：
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作者：
Sutters,Michael
在常染色体显性遗传性多囊肾病（ADPKD）患者中，肾功能恶化，因为肾脏被大量充满液体的囊肿所取代。虽然PKD基因在十年前就被发现了，但从突变到疾病的途径仍然是深入研究的主题。作为这项工作的结果，它已变得明显，多囊蛋白是多功能的蛋白质，在最广泛的意义上，似乎参与了转导的一些环境线索到适当的细胞反应。提示肾小管上皮细胞的去分化可能是膀胱发生的主要致病途径。现有证据表明，多囊蛋白活性的丧失通过几种可能的途径导致细胞钙调节的微妙紊乱。异常的细胞钙稳态可能导致受影响细胞的分化改变。对多囊蛋白的研究揭示了一些对基础细胞生物学的全新见解，但这些尚未令人满意地整合到ADPKD发展的经验证的致病途径中。
In individuals with autosomal dominant polycystic kidney disease (ADPKD), renal function deteriorates as the kidneys become replaced by multitudes of fluid-filled cysts. Although the PKD genes were identified a decade ago, the pathway (s) leading from mutation to disease remain the subject of intense investigation. As a result of this work, it has become apparent that the polycystins are multifunctional proteins that, in the broadest sense, appear to be involved in the transduction of a number of environmental cues into appropriate cellular responses. It is likely that the central pathogenetic pathway for cystogenesis stems from de-differentiation of tubular epithelial cells. Available evidence indicates that loss of polycystin activity leads to subtle derangements of cell calcium regulation through several possible pathways. Abnormal cell calcium homeostasis might then lead to altered differentiation in affected cells. The study of the polycystins has revealed some entirely novel insights into fundamental cell biology but these have not yet been satisfactorily integrated into a verified pathogenetic pathway for the development of ADPKD.