Expression of PKD1 and PKD2 transcripts and proteins in human embryo and during normal kidney development
Expression of PKD1 and PKD2 transcripts and proteins in human embryo and during normal kidney development
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DOI：
10.1016/s0002-9440(10)64919-x
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发表时间：
2002-03-01
影响因子：
6
通讯作者：
Gubler, MC
中科院分区：
文献类型：
--
作者：
Chauvet, V;Qian, F;Gubler, MC
常染色体显性多囊肾病是最常见的人类遗传性疾病之一，具有遗传异质性。大多数病例是由分别编码多囊蛋白-1 或多囊蛋白-2 的 PKD1 或 PKD2 突变引起的。 Polycystin-1 是一种大型跨膜蛋白，包含多个参与细胞-细胞和/或细胞-基质相互作用的结构域。 Polycystin-2 是与某些阳离子通道家族具有同源性的跨膜糖蛋白。尽管有大量报道，但这两种蛋白质，尤其是多囊蛋白-1 的组织分布仍然存在争议。我们使用 Northern blot 分析、原位杂交和免疫组织化学方法研究了 PKD1 和 PKD2 转录本和蛋白质在人类胚胎发生和肾脏发育过程中的表达模式。对于每个基因，转录物和蛋白质的表达模式是一致的。在人类5至6周大的胚胎中，这两个基因广泛表达，主要在神经组织、心肌细胞、内胚层衍生物和中肾中。在这个年龄，在输尿管芽和未诱导的后肾中观察到 PKD2 表达，但未观察到 PKD1 表达。此后，PKD2 在肾单位发育的后期广泛表达，而高 PKD1 表达首先出现在分化的近端小管中。从第 20 周到第 24 周，这两个基因的近曲小管表达均下降。 PKD1 转录本后来在胎儿肾发生中仅限于远端肾小管，在成年肾脏中不再检测到，但仍保持多囊蛋白-1 的微弱表达，而在整个肾发生过程中观察到 PKD2 转录本和蛋白质的持续表达。总体而言，与之前的观察相反，我们发现肾发生过程中 PKD1 和 PKD2 的时空表达存在显着差异，PKD2 比 PKD1 表达更早且更广泛。这些数据表明，多囊蛋白可以与不同的伴侣相互作用，至少在肾脏发育过程中是这样。
Autosomal-dominant polycystic kidney disease, one of the most frequent human genetic disorders, is genetically heterogeneous. Most cases result from mutations of PKD1 or PKD2 encoding polycystin-1 or polycystin-2, respectively. Polycystin-1 is a large transmembrane protein containing several domains involved in cell-cell and/or cell-matrix interactions. Polycystin-2 is transmembrane glycoprotein sharing homology with some families of cation channels. Despite a large number of reports, the tissue distribution of these two proteins, especially of polycystin-1, is still debated. We investigated the expression pattern of PKD1 and PKD2 transcripts and proteins during human embryogenesis and kidney development, using Northern blot analysis, in situ hybridization, and immunohistochemical methods. For each gene, the expression pattern of transcripts and protein was concordant. In human 5- to 6-week-old embryos, both genes are widely expressed, mainly in neural tissue, cardiomyocytes, endodermal derivatives, and mesonephros. At this age, PKD2 but not PKD1 expression is observed in the ureteric bud and the uninduced metanephros. Thereafter, PKD2 is diffusely expressed at aft stages of nephron development, whereas high PKD1 expression first appears in differentiated proximal tubules. Proximal tubule expression of both genes decreases from weeks 20 to 24 onwards. PKD1 transcripts, later restricted to distal tubules in fetal nephrogenesis, are no longer detected in adult kidneys, which nevertheless maintain a faint expression of polycystin-1, whereas persistent expression of PKD2 transcripts and protein is observed throughout nephrogenesis. Overall, contrary to previous observations, we found profound differences in the spatiotemporal expression of PKD1 and PKD2 during nephrogenesis, PKD2 being expressed earlier and more diffusely than PKD1. These data suggest that polycystins could interact with different partners, at least during kidney development.