New Insights into the Molecular Mechanisms Targeting Tubular Channels/Transporters in PKD Development
New Insights into the Molecular Mechanisms Targeting Tubular Channels/Transporters in PKD Development
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DOI：
10.1159/000444839
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发表时间：
2016-03
期刊：
影响因子：
3.7
通讯作者：
Ming Wu;Shengqiang Yu
中科院分区：
文献类型：
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作者：
Ming Wu;Shengqiang Yu
背景资料：常染色体显性多囊肾病（PKD）或常染色体隐性PKD是由PKD 1、PKD 2或PKHD 1基因突变引起的，这些基因分别编码多囊蛋白-1、多囊蛋白-2或纤维囊蛋白。胚胎和出生后的突变研究表明，运输或通道功能失调开始前的囊肿，这表明运输或通道功能的异常在PKD的病理起着至关重要的作用。多囊蛋白-2本身是一种钙离子通道，其通道功能可受多囊蛋白-1或纤维囊蛋白调节。本文就PKD中钙离子转运和环磷酸腺苷（cAMP）驱动的氯离子转运的研究进展作一综述。此外，本文还对葡萄糖转运蛋白、磷酸盐转运蛋白和水通道在PKD中的作用及其机制进行了讨论。关键信息：在PKD的发病机制中，钙处理的异常和大量的cAMP依赖性囊性纤维化跨膜传导调节剂介导的集合管中的液体分泌是最重要的问题。
Background: Autosomal dominant polycystic kidney disease (PKD) or autosomal recessive PKD is caused by a mutation in the PKD1, PKD2 or PKHD1 gene, which encodes polycystin-1, polycystin-2 or fibrocystin, respectively. Embryonic and postnatal mutation studies show that transport or channel function is dysregulated before the initiation of cystogenesis, suggesting that the abnormality of transport or channel function plays a critical role in the pathology of PKD. Summary: Polycystin-2 by itself is a calcium-permeable cation channel, and its channel function can be regulated by polycystin-1 or fibrocystin. In this paper, we reviewed the current knowledge about calcium transports and cyclic adenosine monophosphate (cAMP)-driven chloride transports in PKD. In addition, the function and the underlining mechanism of glucose transporters, phosphate transporters and water channels in PKD are also discussed. Key Messages: Abnormalities in calcium handling and exuberant cAMP-dependent cystic fibrosis transmembrane conductance regulator-mediated fluid secretion in the collecting duct are the most important issues in the pathogenesis of PKD.